Replication of Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes (CANVAS Trial)
Conditions: Diabetes
Sponsor: Brigham and Women's Hospital

Replication of Canagliflozin and Cardiovascular and Renal Events in  
Type 2 Diabetes (CANVAS Trial) 
NCT03936010 
May 27, 2021

Effectiveness research with Real World Data to support FDA’s regulatory decision making 
 
 
1 
 
1. RCT Details 
This section provides a high-level overview of the RCT that the described real-world evidence study is trying to replicate as closely 
as possible given the remaining limitations inherent in the healthcare databases.  
 
1.1 Title 
 
Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes (CANVAS trial) 
 
1.2 Intended aim(s) 
 
To compare canagliflozin to placebo on cardiovascular (CV) events including CV death, heart attack, and stroke in patients 
with type 2 diabetes mellitus (T2DM), whose diabetes is not well controlled at the beginning of the study and who have a 
history of CV events or have a high risk for CV events. 
 
1.3 Primary endpoint for replication and RCT finding 
 
Major Adverse Cardiovascular Events, Including CV Death, Nonfatal Myocardial Infarction (MI), and Nonfatal Stroke 
 
1.4 Required power for primary endpoint and noninferiority margin (if applicable) 
 
With 688 cardiovascular safety events recorded across the trials, there would be at least 90% power, at an alpha level of 
0.05, to exclude an upper margin of the 95% confidence interval for the hazard ratio of 1.3. 
 
1.5 Primary trial estimate targeted for replication 
 
HR = 0.86 (95% CI 0.75–0.97) comparing canagliflozin to placebo (Neal et al., 2017) 
 
 
2. Person responsible for implementation of replication in Aetion 
Ajinkya Pawar, Ph.D. implemented the study design in the Aetion Evidence Platform. S/he is not responsible for the validity of the 
design and analytic choices. All implementation steps are recorded and the implementation history is archived in the platform.   
 
 
3. Data Source(s) 
United/Optum, MarketScan, Medicare  
 

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Effectiveness research with Real World Data to support FDA’s regulatory decision making 
 
 
3 
5. Cohort Identification  
 
5.1 Cohort Summary 
This study will involve a new user, parallel group, cohort study design comparing canagliflozin to the DPP-4 inhibitor (DPP4i) 
antidiabetic class. DPP4is serve as a proxy for placebo, since this class of antidiabetic drugs is not known to have an impact on the 
outcome of interest. The comparison against DPP4 inhibitors is the primary comparison. Initiators of 2nd generation 
sulfonylureas are used as a secondary comparator group. The patients will be required to have continuous enrollment during the 
baseline period of 180 days before initiation of canagliflozin or a comparator drug (cohort entry date). Follow-up for the outcome 
(3P-MACE), begins the day after drug initiation. As in the trial, patients are allowed to take other antidiabetic medications during 
the study. 
 
5.2 Important steps for cohort formation 
 
5.2.1 Eligible cohort entry dates 
Market availability of canagliflozin in the U.S. started on March 29, 2013. 
• For Marketscan and Medicare: April 1, 2013-Dec 31, 2017 (end of data availability).  
• For Optum: April 1, 2013-March 31, 2019 (end of data availability). 
 
 
5.2.2 Specify inclusion/exclusion criteria for cohort entry and define the index date 
 
Inclusion and exclusion criteria were adapted from the trial as closely as possible. Definitions for all inclusion/exclusion are provided 
in Appendix A and are summarized in the flowcharts below. 
 
5.3 Flowchart of the study cohort assembly 
 
For canagliflozin vs. DPP4i 
  
Optum 
Marketscan 
Medicare* 
  
Less 
Excluded 
Patients 
Remaining 
Patients 
Less 
Excluded 
Patients 
Remaining 
Patients 
Less 
Excluded 
Patients 
Remaining 
Patients 
All patients 
  
74,864,884 
  
191,990,035 
  
23,466,175 

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Patients who used exposure or a reference between April 1, 2013 to Dec 
2017 (for Marketscan/Medicare)/March 2019 (for Optum) 
-74,192,962 
671,922 
-
191,172,811 
817,224 
-21,718,863 
1,747,312 
Patients who have continuous 6 months registration in the database  
-89,308 
582,614 
-69,496 
747,728 
-466,595 
1,280,717 
Patients without prior use of reference 
-339,732 
242,882 
-464,089 
283,639 
-810,370 
470,347 
Patients without prior use of exposure 
-75,001 
167,881 
-89,428 
194,211 
-71,119 
399,228 
Excluded because patient qualified in >1 exposure category 
-236 
167,645 
-312 
193,899 
-301 
398,927 
Excluded based on Age 
-7 
167,638 
0 
193,899 
0 
398,927 
Excluded based on Gender 
-8 
167,630 
0 
193,899 
0 
398,927 
Excluded based on Inclusion 1- DM Type 2 with ICD-10 
-5,385 
162,245 
-9,472 
184,427 
-4,090 
394,837 
Excluded based on Inclusion 2- History or high risk of cardiovascular disease 
(with 180 day lookback) 
-25,130 
137,115 
-39,753 
144,674 
-20,833 
374,004 
Excluded based on Inclusion 3- Include all males OR Female 
postmenopausal- >45 years of age OR use of contraceptives 
-7 
137,108 
-9 
144,665 
0 
374,004 
Excluded based on Exclusion 1- DM Type I + Secondary DM + Diabetic 
ketoacidosis with ICD10 CODES 
-4,572 
132,536 
-3,939 
140,726 
-16,980 
357,024 
Excluded based on Exclusion 4- History of one or more severe hypoglycemic 
episode- Severe hypoglycemia (Inpatient, primary) 
-109 
132,427 
-47 
140,679 
-472 
356,552 
Excluded based on Exclusion 5- Glucose-galactose malabsorption/Primary 
Renal glucosuria 
-37 
132,390 
-30 
140,649 
-173 
356,379 
Excluded based on Exclusion #7- Renal disease that requires treatment with 
immunosuppresive therapy 
-1,512 
130,878 
-662 
139,987 
-6,367 
350,012 
Excluded based on Exclusion 8- MI, unstable angina, revascularization 
procedure, or cerebrovascular accident within 3 months 
-2,345 
128,533 
-1,604 
138,383 
-8,548 
341,464 
Excluded based on Exclusion 9- Cardiac conduction 
disorder(inpatient)/Other cardiac dysrhythmia (inpatient) 
-167 
128,366 
-71 
138,312 
-517 
340,947 
Excluded based on Exclusion 10- Liver disease 
-2,303 
126,063 
-1,695 
136,617 
-6,089 
334,858 
Excluded based on Exclusion 11- Any history of or planned bariatric surgery 
(prior 5 years) 
-22 
126,041 
-95 
136,522 
-12 
334,846 
Excluded based on Exclusion 14- History of Malignant Neoplasm (prior 5 
years) 
-4,554 
121,487 
-3,985 
132,537 
-19,311 
315,535 
Excluded based on Exclusion 15- HIV/AIDS (dx and meds) -prior 5 years 
-64 
121,423 
-56 
132,481 
-127 
315,408 
Excluded based on Exclusion 16- Hematological disorder 
-1,540 
119,883 
-1,633 
130,848 
-7,624 
307,784 
Excluded based on Exclusion 17- CCI (180 days) >=10 
-177 
119,706 
-50 
130,798 
-696 
307,088 

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Excluded based on Exclusion 18 - Major Surgery (90 days prior) 
-191 
119,515 
-212 
130,586 
-674 
306,414 
Excluded based on Exclusion 20- Use of SGLT2i (prior 6 months) 
-833 
118,682 
-892 
129,694 
-817 
305,597 
Excluded based on Exclusion 22- use of a corticosteroid medication or 
immunosuppressive agent 
-3,235 
115,447 
-3,085 
126,609 
-8,985 
296,612 
Excluded based on Exclusion 23- Use of cana in prior 3 months (although 
this is already applied as part of cohort creation) 
0 
115,447 
0 
126,609 
0 
296,612 
Excluded based on Exclusion 24- Alcohol or Drug abuse (prior 3 years) and 
Exclusion 25- Pregnancy 
-972 
114,475 
-532 
126,077 
-1,766 
294,846 
Final cohort 
  
114,475 
  
126,077 
  
294,846 
* Medicare database includes only patients with at least one diagnosis for diabetes, heart failure, or cerebrovascular disease. 
**Exclusion 24 and 25 collapsed to adhere to CMS cell suppression guidelines. 
 
 
For canagliflozin vs. 2nd generation SUs 
  
Optum 
Marketscan 
Medicare* 
  
Less 
Excluded 
Patients 
Remaining 
Patients 
Less 
Excluded 
Patients 
Remaining 
Patients 
Less 
Excluded 
Patients 
Remaining 
Patients 
All patients 
  
74,864,884 
  
191,990,035 
  
23,466,175 
Patients who used exposure or a reference between April 1, 2013 to Dec 
2017 (for Marketscan/Medicare)/March 2019 (for Optum) 
-
73,662,096 
1,202,788 
-
190,768,942 
1,221,093 
-
20,351,733 
3,114,442 
Patients who have continuous 6 months registration in the database  
-165,247 
1,037,541 
-115,162 
1,105,931 
-861,454 
2,252,988 
Patients without prior use of reference 
-710,706 
326,835 
-759,153 
346,778 
-1,627,827 
625,161 
Patients without prior use of exposure 
-70,933 
255,902 
-88,833 
257,945 
-68,783 
556,378 
Excluded because patient qualified in >1 exposure category 
-168 
255,734 
-149 
257,796 
-118 
556,260 
Excluded based on Age 
-10 
255,724 
0 
257,796 
0 
556,260 
Excluded based on Gender 
-17 
255,707 
0 
257,796 
0 
556,260 
Excluded based on Inclusion 1- DM Type 2 with ICD-10 
-14,479 
241,228 
-23,583 
234,213 
-8,608 
547,652 
Excluded based on Inclusion 2- History or high risk of cardiovascular disease 
(with 180 day lookback) 
-38,807 
202,421 
-54,172 
180,041 
-30,020 
517,632 
Excluded based on Inclusion 3- Include all males OR Female 
postmenopausal- >45 years of age OR use of contraceptives 
-21 
202,400 
-36 
180,005 
0 
517,632 

Effectiveness research with Real World Data to support FDA’s regulatory decision making: Protocol Template 
 
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Excluded based on Exclusion 1- DM Type I + Secondary DM + Diabetic 
ketoacidosis with ICD10 CODES 
-5,426 
196,974 
-4,290 
175,715 
-19,804 
497,828 
Excluded based on Exclusion 4- History of one or more severe hypoglycemic 
episode- Severe hypoglycemia (Inpatient, primary) 
-76 
196,898 
-37 
175,678 
-332 
497,496 
Excluded based on Exclusion 5- Glucose-galactose malabsorption/Primary 
Renal glucosuria 
-53 
196,845 
-55 
175,623 
-221 
497,275 
Excluded based on Exclusion #7- Renal disease that requires treatment with 
immunosuppresive therapy 
-2,276 
194,569 
-976 
174,647 
-9,763 
487,512 
Excluded based on Exclusion 8- MI, unstable angina, revascularization 
procedure, or cerebrovascular accident within 3 months 
-3,178 
191,391 
-2,244 
172,403 
-11,210 
476,302 
Excluded based on Exclusion 9- Cardiac conduction 
disorder(inpatient)/Other cardiac dysrhythmia (inpatient) 
-240 
191,151 
-121 
172,282 
-837 
475,465 
Excluded based on Exclusion 10- Liver disease 
-3,273 
187,878 
-2,251 
170,031 
-8,410 
467,055 
Excluded based on Exclusion 11- Any history of or planned bariatric surgery 
(prior 5 years) 
-27 
187,851 
-109 
169,922 
-16 
467,039 
Excluded based on Exclusion 14- History of Malignant Neoplasm (prior 5 
years) 
-6,172 
181,679 
-5,306 
164,616 
-25,472 
441,567 
Excluded based on Exclusion 15- HIV/AIDS (dx and meds) -prior 5 years 
-112 
181,567 
-72 
164,544 
-198 
441,369 
Excluded based on Exclusion 16- Hematological disorder 
-1,925 
179,642 
-1,989 
162,555 
-9,438 
431,931 
Excluded based on Exclusion 17- CCI (180 days) >=10 
-287 
179,355 
-50 
162,505 
-993 
430,938 
Excluded based on Exclusion 18 - Major Surgery (90 days prior) 
-317 
179,038 
-291 
162,214 
-856 
430,082 
Excluded based on Exclusion 20- Use of SGLT2i (prior 6 months) 
-904 
178,134 
-984 
161,230 
-874 
429,208 
Excluded based on Exclusion 22- use of a corticosteroid medication or 
immunosuppressive agent 
-4,334 
173,800 
-3,909 
157,321 
-10,920 
418,288 
Excluded based on Exclusion 23- Use of cana in prior 3 months (although 
this is already applied as part of cohort creation) 
0 
173,800 
0 
157,321 
0 
418,288 
Excluded based on Exclusion 24- Alcohol or Drug abuse (prior 3 years) and 
Exclusion 25- Pregnancy 
-1566 
172,234 
-777 
156,544 
-2,592 
415,696 
Final cohort 
  
172,234 
  
156,544 
  
415,696 
* Medicare database includes only patients with at least one diagnosis for diabetes, heart failure, or cerebrovascular disease. 
** Exclusion 24 and 25 collapsed to adhere to CMS cell suppression guidelines. 
 
6. Variables  
 
6.1 Exposure-related variables:  

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7 
 
Study drug:  
The study exposure of interest is initiation of canagliflozin. Initiation will be defined by no use of any SGLT-2 inhibitor or a 
comparator in the prior 6 months before treatment initiation (washout period). 
 
Comparator agents: 
• Initiators of canagliflozin will be compared to initiators of- 
o DPP4i (primary) 
o 2nd generation sulfonylureas 
 
Because canagliflozin and comparators are frequently used as second or third line treatments of T2DM, we expect it to be unlikely 
that canagliflozin and comparators are initiated in patients with substantially different baseline risk for proposed outcomes.  
 
6.2 Preliminary Covariates: 
• Age 
• Sex 
• Combined Comorbidity Index (CCI), measured over the default baseline covariate assessment period, defined as 180 days 
prior to and including index date 
 
Covariates listed above represent only a small subset of covariates that will ultimately be controlled for in the design and analysis. 
We use the covariates above only for initial feasibility analyses to judge whether there is likely to be sufficient overlap between 
treatment groups to proceed with the study. Remaining covariates are defined only after the study has passed the initial feasibility 
analysis and the initial power assessment and are listed in Table 1 (Appendix B). These covariates are based on those used by 
Patorno et al. (2019). 
 
6.3 Outcome variables and study follow-up:  
 
6.3.1 Outcome variables 
 
Effectiveness outcomes of interest (definitions provided in Appendix A):  

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• Primary outcome: 3-point major adverse cardiovascular events (MACE), i.e., non-fatal myocardial infarction, non-fatal stroke, 
or CV mortality 
• Secondary outcomes: Individual components: 
o Hospital admission for MI (for purposes of this individual component, fatal MI is included) 
o Hospital admission for stroke (for purposes of this individual component, fatal stroke is included) 
o All-cause mortality/CV mortality: 
§ All-cause inpatient mortality identified using discharge status codes will be used as a proxy for “CV mortality” 
in commercial databases 
§ Information on CV mortality through data linkage with the National Death Index (NDI) will only become 
available at a later date for Medicare and will be used in secondary analyses. 
 
Control outcomes of interest (control outcomes only serve to assess aspects of study validity but are not further interpreted):  
1. Diabetes Ketoacidosis (we expect to see a positive association; Neal et al., 2017) 
2. Heart failure (we expect to see a protective effect; Neal et al., 2017) 
Control outcome definitions 
 
6.3.2 Study follow-up 
Both as-treated (AT) and intention-to-treat (ITT) analyses will be conducted with treatment defined as the index drug on the day of 
cohort entry. Because adherence in the real world databases is expected to be much worse than in the trial, the AT analysis is the 
primary analysis, as it targets the relative hazard of outcomes on treatment.  
 
For the AT analyses, the follow-up will start the day after initiation of canagliflozin and comparator and will continue until the 
earliest date of the following events: 
• The first occurrence of the outcome of interest, unless otherwise specified for selected outcomes,  
Outcome 
Definition 
Comments 
Control Outcomes 
Diabetic Ketoacidosis 
Inpatient ICD-9 diagnosis: 250.1x 
 
Note- The  corresponding ICD-10 codes 
will also be used  
Heart Failure 
Inpatient ICD-9 diagnosis (primary diagnosis):  
428.x, 398.91, 402.01, 402.11, 402.91, 404.01, 404.11, 404.91, 404.03, 404.13, 404.93 
Note- The  corresponding ICD-10 codes 
will also be used  

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• The date of end of continuous registration in the database, 
• End of the study period, 
• Measured death event occurs, 
• Nursing home admission 
o Nursing home admissions are considered a censoring event because the data sources utilized typically provide little to 
no data on a patient, particularly on drug utilization, after admission. We will utilize this as an exclusion reason for 
cohorts for the same reason. 
• The date of drug discontinuation, defined as the date of the last continuous treatment episode of the index drug 
(canagliflozin and comparator) plus a defined grace period (i.e., 30 days after the end of the last prescription’s days’ supply in 
main analyses). 
• The date of augmentation or switching from an exposure to a comparator or any other agent in the comparator class and 
vice versa (e.g. switching from saxagliptin to linagliptin would be a censoring event); 
o A dosage change on the index treatment does not fulfill this criterion 
o An added treatment that is not part of the exposure or comparator group does not fulfill this criterion (e.g. if a 
canagliflozin user adds insulin, he or she does not get censored at the time of insulin augmentation) 
 
For the ITT analyses, the censoring based on the augmentation/switching and treatment discontinuation will be replaced with a 
maximum allowed follow-up time of 365 days.  
 
7. Initial Feasibility Analysis  
 
Aetion report name: 
For canagliflozin vs. DPP4i 
Optum- https://bwh-dope.aetion.com/#/projects/details/660/results/26056/result/0  
Marketscan- https://bwh-dope.aetion.com/#/projects/details/661/results/26057/result/0  
Medicare- https://bwh-dope.aetion.com/#/projects/details/662/results/26055/result/0  
 
For canagliflozin vs. 2nd generation SUs 
Optum- https://bwh-dope.aetion.com/#/projects/details/660/results/26064/result/0  
Marketscan- https://bwh-dope.aetion.com/#/projects/details/661/results/26065/result/0  
Medicare- https://bwh-dope.aetion.com/#/projects/details/662/results/26066/result/0  

Effectiveness research with Real World Data to support FDA’s regulatory decision making: Protocol Template 
 
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Date conducted: 09/30/2018 
 
Complete Aetion feasibility analysis using age, sex, and CCI as the only covariates and the primary endpoint (Section 6.3.1) as the 
outcome. No measures of association will be computed nor will incidence rates stratified by treatment group.  
 
• Report patient characteristics by treatment group 
• Report summary parameters of the overall study population 
• Report median follow-up time by treatment group 
• Report reasons for censoring in the overall study population 
 
 
8. Initial Power Assessment 
 
Aetion report name: 
• For canagliflozin vs. DPP4i 
Optum- https://bwh-dope.aetion.com/#/projects/details/660/results/26064/result/0  
 
Marketscan- https://bwh-dope.aetion.com/#/projects/details/661/results/26065/result/0  
Medicare- https://bwh-dope.aetion.com/#/projects/details/662/results/26066/result/0  
 
• For canagliflozin vs. 2nd generation Sus 
Optum- https://bwh-dope.aetion.com/#/projects/details/660/results/26067/result/0  
Marketscan- https://bwh-dope.aetion.com/#/projects/details/661/results/26068/result/0  
Medicare- https://bwh-dope.aetion.com/#/projects/details/662/results/26069/result/0  
 
Date conducted: 09/30/2018 
 
In order to complete the initial power analysis, the dummy outcome of a 90-day gap in database enrollment will be used. This 
outcome is used to ensure that no information on the comparative risks of the outcomes of interest are available at this stage. 
Complete a 1:1 PS-matched comparative analysis using this outcome. PS should include only 3 covariates: age, sex, and combined 
comorbidity index. Power calculations are based on the formulas from Chow et al. (2008). 
 

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• Stop analyses until feasibility and power are reviewed by primary investigators and FDA. Reviewers evaluate the results of the 
analyses described above in Sections 7 and 8, including numbers of patients, patient characteristics, follow-up time, and reasons 
for censoring by treatment group, as well as overall rates of outcomes and study power. These parameters are re-evaluated and 
reported in the subsequent sections, after incorporating feedback and refining the protocol. 
Reviewed by PI: 
Jessica M. Franklin 
Date reviewed: 
10/26/18 
Reviewed by FDA: 
Ken Quinto 
Date reviewed: 
12/11/18 
Reasons for stopping 
analysis (if required): 
 
 
 
9. Balance Assessment after PS matching 
 
Aetion report name: 
For canagliflozin vs. DPP4i 
o Optum- https://bwh-dope.aetion.com/projects/details/660/results/44837/result/0 
o Marketscan-  https://bwh-dope.aetion.com/projects/details/661/results/44838/result/0 
o Medicare- https://bwh-dope.aetion.com/projects/details/662/results/44839/result/0 
For canagliflozin vs. 2nd generation SUs 
o Optum- https://bwh-dope.aetion.com/projects/details/660/results/44834/result/0 
o Marketscan- https://bwh-dope.aetion.com/projects/details/661/results/44835/result/0 
o Medicare- https://bwh-dope.aetion.com/projects/details/662/results/44836/result/0 
 
Date conducted: 11/18/2019 
 
After review of initial feasibility and power analyses, complete creation of the remaining covariates (see Table 1 below for list of 
covariates). Again, using the dummy outcome of a 90-day gap in database enrollment, complete a 1:1 PS-matched analysis. The PS 
should include the complete list of covariates (excluding laboratory values, which are missing in some patients). 
 
• Provide plot of PS distributions stratified by treatment group. 
 
Note- Please refer to Appendix B. 
 

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• Report covariate balance after matching. 
 
Note- For Table 1, please refer to Appendix B.  
 
• Report reasons for censoring by treatment group. 
o For canagliflozin vs. DPP4i 
  
Overall 
Referent 
Exposure 
Dummy Outcome 
0 (0.00%) 
0 (0.00%) 
0 (0.00%) 
Death 
589 (0.39%) 
374 (0.49%) 
215 (0.28%) 
Start of an additional exposure 
6,913 (4.54%) 
2,413 (3.17%) 
4,500 (5.91%) 
End of index exposure 
98,215 (64.53%) 
47,931 (62.98%) 
50,284 (66.08%) 
Specified date reached 
22,353 (14.69%) 
12,162 (15.98%) 
10,191 (13.39%) 
End of patient enrollment 
19,170 (12.60%) 
9,407 (12.36%) 
9,763 (12.83%) 
Switch to other DPP4i (for censoring) + nursing home 
admission 
4,962 (3.26%) 
3,814 (5.01%) 
1,148 (1.51%) 
 
o For canagliflozin vs. 2nd generation SUs 
  
Overall 
Referent 
Exposure 
Dummy Outcome 
0 (0.00%) 
0 (0.00%) 
0 (0.00%) 
Death 
548 (0.40%) 
364 (0.53%) 
184 (0.27%) 
Start of an additional exposure 
6,001 (4.36%) 
1,842 (2.68%) 
4,159 (6.04%) 
End of index exposure 
85,900 (62.38%) 
41,024 (59.58%) 
44,876 (65.18%) 
Specified date reached 
22,281 (16.18%) 
12,957 (18.82%) 
9,324 (13.54%) 
End of patient enrollment 
18,853 (13.69%) 
9,660 (14.03%) 
9,193 (13.35%) 
Switch to other SUs (for censoring) + nursing home admission 
4,117 (2.99%) 
3,003 (4.36%) 
1,114 (1.62%) 
 
• Report follow-up time by treatment group. 
o For canagliflozin vs. DPP4i 
Median Follow-Up Time (Days) [IQR] 
Patient Group 
Optum 
Marketscan 
Medicare 
Overall Patient Population 
127 [58-306] 
149 [72-341] 
147 [81-318] 

Effectiveness research with Real World Data to support FDA’s regulatory decision making 
 
 
13 
Referent 
121 [58-297] 
153 [87-327] 
153 [87-327] 
Exposure 
134 [58-318] 
142 [58-310] 
142 [58-310] 
 
o For canagliflozin vs. 2nd generation SUs 
Median Follow-Up Time (Days) [IQR] 
Patient Group 
Optum 
Marketscan 
Medicare 
Overall Patient Population 
141 [63-336] 
159 [83-358] 
172 [90-373] 
Referent 
140 [75-330] 
200 [118-414] 
200 [118-414] 
Exposure 
141 [58-341] 
144 [62-327] 
144 [62-327] 
 
• Report risk per 1,000 patients 
 
Aetion report name: 
• For canagliflozin vs. DPP4i 
Optum- https://bwh-dope.aetion.com/#/projects/details/660/results/34590/result/0 
Marketscan- https://bwh-dope.aetion.com/#/projects/details/661/results/34591/result/0 
Medicare- https://bwh-dope.aetion.com/#/projects/details/662/results/34592/result/0 
 
• For canagliflozin vs. 2nd generation SUs 
Optum- https://bwh-dope.aetion.com/#/projects/details/660/results/34596/result/0 
Marketscan- https://bwh-dope.aetion.com/#/projects/details/661/results/34597/result/0 
Medicare- https://bwh-dope.aetion.com/#/projects/details/662/results/34598/result/0 
 
Date conducted: 04/25/2019 
For canagliflozin vs. DPP4i 
  
Optum 
Marketscan 
Medicare 
Risk per 1,000 patients 
7.58 
7.81 
22.56 
 
For canagliflozin vs. 2nd generation SUs 
  
Optum 
Marketscan 
Medicare 
Risk per 1,000 patients 
9.71 
9.39 
27.67 

Effectiveness research with Real World Data to support FDA’s regulatory decision making: Protocol Template 
 
14 
 
 
10. Final Power Assessment 
 
Date conducted: 12/01/2019 
 
• Re-calculate power in the appropriate excel table, using the revised number of matched patients from the PS-match in Section 9. 
All other parameters in the table should be the same as in Section 8. If the study is to be implemented in more than one 
database, copy and paste excel sheet to report power for each database separately and for the pooled analysis that uses data 
from all databases together. Power calculations are based on the formulas from Chow et al. (2008). 
 
o For canagliflozin vs. DPP4i 
§ Pooled 
 
 
§ Optum 
Superiority Analysis
Number of patients matched
Reference
76,101
Exposed
76,101
Risk per 1,000 patients
12.65
Desired HR from RCT
0.86
Alpha (2-sided)
0.05
Number of events expected
1925.3553
Power
0.911332398
Non-inferiority Analysis
Number of patients matched
Reference
76,101
Exposed
76,101
Risk per 1,000 patients
12.65
Assumed HR from RCT
1
Alpha (2-sided)
0.05
Non-inferiority margin
1.3
Number of events expected
1925.3553
Power
0.999926523

Effectiveness research with Real World Data to support FDA’s regulatory decision making 
 
 
15 
 
 
§ 
Marketscan 
 
 
§ 
Medicare 
Superiority Analysis
Number of patients matched
Reference
19,532
Exposed
19,532
Risk per 1,000 patients
7.58
Desired HR from RCT
0.86
Alpha (2-sided)
0.05
Number of events expected
296.10512
Power
0.254449294
Non-inferiority Analysis
Number of patients matched
Reference
19,532
Exposed
19,532
Risk per 1,000 patients
7.58
Assumed HR from RCT
1
Alpha (2-sided)
0.05
Non-inferiority margin
1.3
Number of events expected
296.10512
Power
0.616911596
Superiority Analysis
Number of patients matched
Reference
23,168
Exposed
23,168
Risk per 1,000 patients
7.58
Desired HR from RCT
0.86
Alpha (2-sided)
0.05
Number of events expected
351.22688
Power
0.292672624
Non-inferiority Analysis
Number of patients matched
Reference
23,168
Exposed
23,168
Risk per 1,000 patients
7.58
Assumed HR from RCT
1
Alpha (2-sided)
0.05
Non-inferiority margin
1.3
Number of events expected
351.22688
Power
0.690943556

Effectiveness research with Real World Data to support FDA’s regulatory decision making: Protocol Template 
 
16 
 
 
o For canagliflozin vs. 2nd generation SUs 
§ 
Pooled 
 
 
§ 
Optum 
Superiority Analysis
Number of patients matched
Reference
33,401
Exposed
33,401
Risk per 1,000 patients
22.56
Desired HR from RCT
0.86
Alpha (2-sided)
0.05
Number of events expected
1507.05312
Power
0.833370249
Non-inferiority Analysis
Number of patients matched
Reference
33,401
Exposed
33,401
Risk per 1,000 patients
22.56
Assumed HR from RCT
1
Alpha (2-sided)
0.05
Non-inferiority margin
1.3
Number of events expected
1507.05312
Power
0.999133759
Superiority Analysis
Number of patients matched
Reference
68,850
Exposed
68,850
Risk per 1,000 patients
15.59
Desired HR from RCT
0.86
Alpha (2-sided)
0.05
Number of events expected
2146.743
Power
0.937493971
Non-inferiority Analysis
Number of patients matched
Reference
68,850
Exposed
68,850
Risk per 1,000 patients
15.59
Assumed HR from RCT
1
Alpha (2-sided)
0.05
Non-inferiority margin
1.3
Number of events expected
2146.743
Power
0.999980899

Effectiveness research with Real World Data to support FDA’s regulatory decision making 
 
 
17 
 
 
§ 
Marketscan 
 
 
§ 
Medicare 
Superiority Analysis
Number of patients matched
Reference
16,740
Exposed
16,740
Risk per 1,000 patients
9.71
Desired HR from RCT
0.86
Alpha (2-sided)
0.05
Number of events expected
325.0908
Power
0.274612159
Non-inferiority Analysis
Number of patients matched
Reference
16,740
Exposed
16,740
Risk per 1,000 patients
9.71
Assumed HR from RCT
1
Alpha (2-sided)
0.05
Non-inferiority margin
1.3
Number of events expected
325.0908
Power
0.657366306
Superiority Analysis
Number of patients matched
Reference
23,265
Exposed
23,265
Risk per 1,000 patients
9.39
Desired HR from RCT
0.86
Alpha (2-sided)
0.05
Number of events expected
436.9167
Power
0.350813593
Non-inferiority Analysis
Number of patients matched
Reference
23,265
Exposed
23,265
Risk per 1,000 patients
9.39
Assumed HR from RCT
1
Alpha (2-sided)
0.05
Non-inferiority margin
1.3
Number of events expected
436.9167
Power
0.782915462

Effectiveness research with Real World Data to support FDA’s regulatory decision making: Protocol Template 
 
18 
 
 
• Stop analyses until balance and final power assessment are reviewed by primary investigators, FDA, and assigned members of 
advisory board. Reviewers evaluate the results of the analyses described above in Sections 9 and 10, including numbers of 
patients, balance in patient characteristics, follow-up time, and reasons for censoring by treatment group, as well as overall rates 
of outcomes and study power. 
Reviewed by PI: 
Jessica Franklin 
Date reviewed: 
12/9/19 
Reviewed by FDA: 
Ken Quinto 
Date reviewed: 
12/20/19 
Reasons for stopping 
analysis (if required): 
 
 
11. Study Confidence and Concerns 
 
Deadline for voting on study confidence and listing concerns: 12/20/19 
 
• If final feasibility and power analyses are reviewed and approved, proceed to the remaining protocol steps. 
• All study team and advisory board members that review this protocol should at this stage provide their level of confidence for the 
success of the RWD study in the Google Form. This form also provides space for reviewers to list any concerns that they feel may 
Superiority Analysis
Number of patients matched
Reference
28,845
Exposed
28,845
Risk per 1,000 patients
27.67
Desired HR from RCT
0.86
Alpha (2-sided)
0.05
Number of events expected
1596.2823
Power
0.853826925
Non-inferiority Analysis
Number of patients matched
Reference
28,845
Exposed
28,845
Risk per 1,000 patients
9.39
Assumed HR from RCT
1
Alpha (2-sided)
0.05
Non-inferiority margin
1.3
Number of events expected
541.7091
Power
0.86285876

Effectiveness research with Real World Data to support FDA’s regulatory decision making 
 
 
19 
contribute to a failure to replicate the findings of the RCT, including differences in study populations, poor measurement of study 
variables, or residual confounding. All responses will be kept confidential and individual-level results will only be shared with the 
individual respondent. 
 
12. Register study protocol on clinicalTrials.gov 
 
Date conducted:    
 
• Register the study on clinicalTrials.gov and upload this document. 
 
13. Comparative Analyses 
 
Aetion report name: 
Date conducted:    
 
13.1 
For primary analysis:  
 
• In the PS-matched cohort of canagliflozin and DPP4i initiators from Section 9, calculate the HR for each outcome for canagliflozin 
versus referent patients using a Cox proportional hazards model.  
 
13.2 
For secondary analyses: 
 
• In the PS-matched cohort of canagliflozin and 2nd generation SU initiators from Section 9, calculate the HR for canagliflozin versus 
referent patients using a Cox proportional hazards model.  
• In both pre-matched cohorts, perform asymmetrical trimming to remove patients with PS values below the 2.5th percentile of 
treated patients and above the 97.5th percentile of untreated patients. In the trimmed cohort, calculate the HR for canagliflozin 
versus referent patients using a Cox proportional hazards model, adjusting for deciles of the PS. 
 
 

Effectiveness research with Real World Data to support FDA’s regulatory decision making: Protocol Template 
 
20 
14.  Requested Results  
 
14.1 
Results from primary and secondary analyses: 
 
Separately for each endpoint and each comparator group: 
Analysis 
No. exposed events 
No. referent events 
Exposed rate 
Referent rate 
HR (95% CI) 
Crude 
 
 
 
 
 
Primary analysis 
 
 
 
 
 
Analysis 2 
 
 
 
 
 
... 
 
 
 
 
 
HR, Hazard Ratio; CI, Confidence Interval. 
 
15. References 
 
American Diabetes Association. 8. Pharmacologic Approaches to Glycemic Treatment: Standards of Medical Care in Diabetes-2018. 
Diabetes Care. 2018;41(Suppl 1):S73-S85. doi:10.2337/dc18-S008. 
 
Chow S, Shao J, Wang H. 2008.  Sample Size Calculations in Clinical Research. 2nd Ed. Chapman & Hall/CRC Biostatistics Series. page 
177 
 
Neal B, Perkovic V, Mahaffey KW, De Zeeuw D, Fulcher G, Erondu N, Shaw W, Law G, Desai M, Matthews DR. Canagliflozin and 
cardiovascular and renal events in type 2 diabetes. New England Journal of Medicine. 2017; 377(7):644-57. 
 
Patorno E, Pawar A, Franklin JM, et al. Empagliflozin and the Risk of Heart Failure Hospitalization in Routine Clinical Care: A First 
Analysis from the Empagliflozin Comparative Effectiveness and Safety (EMPRISE) Study. Circulation. 2019; in press. 
(https://www.ahajournals.org/doi/pdf/10.1161/CIRCULATIONAHA.118.039177)  
  
 

Effectiveness research with Real World Data to support FDA’s regulatory decision making 
 
 
21 
  
 

#
CANVAS trial definitions 
Implementation in routine care
References/Rationale
Color coding
Please see the following Google Drive for further details or any missing information: 
https://drive.google.com/open?id=1WD618wrywYjEaXzfLTcuK-VCcnb6b-gV
Criteria
ICD-10 codes are not listed in this document because of excel cell size limitations and 
excessive number of ICD-10 codes. Full ICD-10 code lists will be available in the above 
Google Drive Folder (link above). ICD-9 to ICD-10 code conversions were completed 
using a SAS macro that implements forward/ backward mapping based on the CMS ICD-9 
to ICD-10 mapping: https://www.nber.org/data/icd9-icd-10-cm-and-pcs-crosswalk-
general-equivalence-mapping.html
Adequate mapping in claims
Canagliflozin vs. placebo 
Canagliflozin vs. DPP4 inhibitors (primary comparison) or vs. 2nd generation sulfonylureas (secondary)
Patorno, Elisabetta et al. "Cardiovascular outcomes associated with canagliflozin versus 
other non-gliflozin antidiabetic drugs: population based cohort study." BMJ 
2018;360:k119 http://dx.doi.org/10.1136/bmj.k119
Intermediate mapping in claims
Poor mapping or cannot be measured in claims 
Major Adverse Cardiovascular Events, Including CV Death, Nonfatal Myocardial Infarction (MI), and Nonfatal Stroke HR = 0.86 (95% CI 
0.75–0.97)
Measured 1 days after drug initiation in diagnosis position specified below and inpatient care setting:
Inpatient mortality/MI/Stroke --
For MI
Any diagnosis position in inpatient care setting
ICD-9 Dx 410.X (acute myocardial infarction) excluding 410.x2 (subsequent episode of care)
For stroke
Primary diagnosis position in inpatient care setting 
ICD-9 discharge diagnosis:
430.xx  Subarachnoid hemorrhage (SAH)
431.xx  Intracerebral hemorrhage (ICH)
433.x1  Occlusion and stenosis of precerebral arteries with cerebral infarction
434.xx (excluding 434.x0)  Occlusion and stenosis of cerebral arteries with cerebral infarction
436.x  Acute, but ill-defined cerebrovascular events
Mortality- See Mortality Sheet.
For MI: 
PPV 94% in Medicare claims data [Kiyota Y, Schneeweiss S, Glynn RJ, Cannuscio CC, 
Avorn J, Solomon DH. Accuracy of Medicare claims-based diagnosis of acute myocardial 
infarction: estimating positive predictive value on the basis of review of hospital records. 
American heart journal 2004;148:99-104.]
PPV 88.4% in commercially-insured population [Wahl PM, Rodgers K, Schneeweiss S, et 
al. Validation of claims-based diagnostic and procedure codes for cardiovascular and 
gastrointestinal serious adverse events in a commercially-insured population. 
Pharmacoepidemiology and Drug Safety 2010;19:596-603.]
For stroke:
PPV of 85% or higher for ischemic stroke
PPV ranging from 80% to 98% for hemorrhagic stroke
[Andrade SE, Harrold LR, Tjia J, et al. A systematic review of validated methods for 
identifying cerebrovascular accident or transient ischemic attack using administrative 
data. Pharmacoepidemiology and Drug Safety 2012;21 Suppl 1:100-28.]
[Tirschwell DL, Longstreth WT, Jr. Validating administrative data in stroke research. 
Stroke; a journal of cerebral circulation 2002;33:2465-70.]
[Roumie CL, Mitchel E, Gideon PS, Varas-Lorenzo C, Castellsague J, Griffin MR. Validation 
of ICD-9 codes with a high positive predictive value for incident strokes resulting in 
hospitalization using Medicaid health data. Pharmacoepidemiology and drug safety 
2008;17:20-6.]
Can't be measured in claims but not important for the analysis
Man or woman with a diagnosis of type 2 diabetes with glycated hemoglobin level ≥7.0% to
≤10.5% at screening and be either-
Patients with a diagnosis of T2DM (ICD-9 Dx code of 250.x0 or 250.x2) in the 180 days prior to drug 
initiation in any diagnosis position and inpatient or outpatient care setting.
Patorno, Elisabetta et al. "Cardiovascular outcomes associated with canagliflozin versus 
other non-gliflozin antidiabetic drugs: population based cohort study." BMJ 
2018;360:k119 http://dx.doi.org/10.1136/bmj.k119
Patorno, Elisabetta et al. "Empagliflozin and the Risk of Heart Failure Hospitalization in 
Routine Clinical Care: A First Analysis from the Empagliflozin Comparative Effectiveness and 
Safety (EMPRISE) Study."  Circulation. 2019 Apr 8. doi: 
10.1161/CIRCULATIONAHA.118.039177
o   (1) not currently on antihyperglycemic agent (AHA) therapy or 
o   (2) on AHA monotherapy or combination therapy with any approved class of
agents: e.g., sulfonylurea, metformin, peroxisome proliferator-activated receptor gamma
(PPARγ) agonist, alpha-glucosidase inhibitor, glucagon-like peptide-1 (GLP-1) analogue,
dipeptidyl peptidase-4 (DPP-4) inhibitor, or insulin.
2 History or high risk of cardiovascular disease defined on the basis of either:
– Age ≥30 years with documented symptomatic atherosclerotic cardiovascular disease:
Age ≥30 years at drug initiation 
o          including stroke; 
Measured 180 days prior to drug initiation in any diagnosis position and inpatient or outpatient care 
setting- Any stroke: ICD-9 Dx: 430.xx, 431.xx, 433.xx, 434.xx, 436.xx
Patorno, Elisabetta et al. "Cardiovascular outcomes associated with canagliflozin versus 
other non-gliflozin antidiabetic drugs: population based cohort study." BMJ 
2018;360:k119 http://dx.doi.org/10.1136/bmj.k119
Patorno, Elisabetta et al. "Empagliflozin and the Risk of Heart Failure Hospitalization in 
Routine Clinical Care: A First Analysis from the Empagliflozin Comparative Effectiveness and 
Safety (EMPRISE) Study."  Circulation. 2019 Apr 8. doi: 
10.1161/CIRCULATIONAHA.118.039177
o          or myocardial infarction (MI); 
Measured 180 days prior to drug initiation in any diagnosis position and inpatient or outpatient care 
setting-  Acute MI ICD-9 410.xx, Old MI: 412.xx
Patorno, Elisabetta et al. "Cardiovascular outcomes associated with canagliflozin versus 
other non-gliflozin antidiabetic drugs: population based cohort study." BMJ 
2018;360:k119 http://dx.doi.org/10.1136/bmj.k119
Patorno, Elisabetta et al. "Empagliflozin and the Risk of Heart Failure Hospitalization in 
Routine Clinical Care: A First Analysis from the Empagliflozin Comparative Effectiveness and 
Safety (EMPRISE) Study."  Circulation. 2019 Apr 8. doi: 
10.1161/CIRCULATIONAHA.118.039177
o          or hospital admission for unstable angina;
Measured 180 days prior to drug initiation in the Inpatient care setting with ICD-9 discharge diagnosis 
411.xx 
Patorno, Elisabetta et al. "Cardiovascular outcomes associated with canagliflozin versus 
other non-gliflozin antidiabetic drugs: population based cohort study." BMJ 
2018;360:k119 http://dx.doi.org/10.1136/bmj.k119
Patorno, Elisabetta et al. "Empagliflozin and the Risk of Heart Failure Hospitalization in 
Routine Clinical Care: A First Analysis from the Empagliflozin Comparative Effectiveness and 
Safety (EMPRISE) Study."  Circulation. 2019 Apr 8. doi: 
10.1161/CIRCULATIONAHA.118.039177
PRIMARY OUTCOME
Trial details- Secondary indication, 4a- unintended superiority with label change 
1
EXPOSURE vs. COMPARISON
INCLUSION CRITERIA
Depending on the comparison group, we will require new-use (defined as no use 180 days prior to index 
date) of canagliflozin and a comparator drug 
Appendix A

o          or coronary artery bypass graft (CABG); 
CABG:
Measured 180 days prior to drug initiation in any diagnosis position and inpatient care setting - CPT-4: 
33510 – 33536, 33545, 33572. 
       OR – 
Measured 180 days prior to drug initiation in any diagnosis position and inpatient or outpatient care 
setting - ICD-9 procedure: 36.1x, 36.2x
Patorno, Elisabetta et al. "Cardiovascular outcomes associated with canagliflozin versus 
other non-gliflozin antidiabetic drugs: population based cohort study." BMJ 
2018;360:k119 http://dx.doi.org/10.1136/bmj.k119
Patorno, Elisabetta et al. "Empagliflozin and the Risk of Heart Failure Hospitalization in 
Routine Clinical Care: A First Analysis from the Empagliflozin Comparative Effectiveness and 
Safety (EMPRISE) Study."  Circulation. 2019 Apr 8. doi: 
10.1161/CIRCULATIONAHA.118.039177
o          or percutaneous coronary intervention (PCI; with or without stenting); 
PTCA:
Measured 180 days prior to drug initiation in any procedure position and inpatient care setting - CPT-4: 
92973, 92982, 92984, 92995, 92996, 92920 – 92921, 92924 – 92925, 92937, 92938, 92941, 92943, 
92944
OR –
Measured 180 days prior to drug initiation in any procedure position and inpatient or outpatient care 
setting - ICD-9 procedure: 00.66, 36.01, 36.02, 36.03, 36.05, 36.09
Stenting:
Measured 180 days prior to drug initiation in any procedure position and inpatient care setting- CPT-4:  
92980, 92981, 92928 – 92929, 92933 - 92934
OR –
Measured 180 days prior to drug initiation in any procedure position and inpatient or outpatient  care 
setting- ICD-9 procedure: 36.06, 36.07
Patorno, Elisabetta et al. "Cardiovascular outcomes associated with canagliflozin versus 
other non-gliflozin antidiabetic drugs: population based cohort study." BMJ 
2018;360:k119 http://dx.doi.org/10.1136/bmj.k119
Patorno, Elisabetta et al. "Empagliflozin and the Risk of Heart Failure Hospitalization in 
Routine Clinical Care: A First Analysis from the Empagliflozin Comparative Effectiveness and 
Safety (EMPRISE) Study."  Circulation. 2019 Apr 8. doi: 
10.1161/CIRCULATIONAHA.118.039177
o          or peripheral revascularization (angioplasty or surgery);
Measured 180 days prior to drug initiation in any diagnosis position and inpatient or outpatient care 
setting - ICD-9 39.25, 39.50, 39.99.
Patorno, Elisabetta et al. "Cardiovascular outcomes associated with canagliflozin versus 
other non-gliflozin antidiabetic drugs: population based cohort study." BMJ 
2018;360:k119 http://dx.doi.org/10.1136/bmj.k119
Patorno, Elisabetta et al. "Empagliflozin and the Risk of Heart Failure Hospitalization in 
Routine Clinical Care: A First Analysis from the Empagliflozin Comparative Effectiveness and 
Safety (EMPRISE) Study."  Circulation. 2019 Apr 8. doi: 
10.1161/CIRCULATIONAHA.118.039177
o          or symptomatic with documented hemodynamically-significant carotid or peripheral vascular disease; 
Measured 180 days prior to drug initiation in any diagnosis position and inpatient or outpatient care 
setting -
ICD9 diagnosis:
440.20 – 440.24, 440.29 – 440.32,  440.3, 440.4, 443.9  
Patorno, Elisabetta et al. "Cardiovascular outcomes associated with canagliflozin versus 
other non-gliflozin antidiabetic drugs: population based cohort study." BMJ 
2018;360:k119 http://dx.doi.org/10.1136/bmj.k119
Patorno, Elisabetta et al. "Empagliflozin and the Risk of Heart Failure Hospitalization in 
Routine Clinical Care: A First Analysis from the Empagliflozin Comparative Effectiveness and 
Safety (EMPRISE) Study."  Circulation. 2019 Apr 8. doi: 
10.1161/CIRCULATIONAHA.118.039177
o          or amputation secondary to vascular disease.
Measured 180 days prior to drug initiation in any diagnosis position and inpatient or outpatient care 
setting-
Lower extremity amputation   ICD-9 diagnosis: V49.7x 
ICD-9 procedure: 84.10-84.18
CPT: 27590, 27591, 27592, 27880, 27881, 27882, 27884, 27886, 27888, 27889, 28800, 28805, 
28810, 28820, 28825
Patorno, Elisabetta et al. "Cardiovascular outcomes associated with canagliflozin versus 
other non-gliflozin antidiabetic drugs: population based cohort study." BMJ 
2018;360:k119 http://dx.doi.org/10.1136/bmj.k119
Patorno, Elisabetta et al. "Empagliflozin and the Risk of Heart Failure Hospitalization in 
Routine Clinical Care: A First Analysis from the Empagliflozin Comparative Effectiveness and 
Safety (EMPRISE) Study."  Circulation. 2019 Apr 8. doi: 
10.1161/CIRCULATIONAHA.118.039177
– Age ≥50 years with 2 or more of the following risk factors determined at the screening
visit: 
Age ≥50 years at drug initiation 
o          duration of type 2 diabetes of 10 years or more
N/A
We can't capture diabetes duration but will match on number of antidiabetic drugs during 
baseline
o         or systolic blood pressure >140 mmHg (average of 3 readings) recorded at the screening visit
Measured 180 days prior to drug initiation in any diagnosis position and inpatient or outpatient care 
setting - 
Hypertension ICD-9 codes 401.x – 405.x 
Patorno, Elisabetta et al. "Cardiovascular outcomes associated with canagliflozin versus 
other non-gliflozin antidiabetic drugs: population based cohort study." BMJ 
2018;360:k119 http://dx.doi.org/10.1136/bmj.k119
Patorno, Elisabetta et al. "Empagliflozin and the Risk of Heart Failure Hospitalization in 
Routine Clinical Care: A First Analysis from the Empagliflozin Comparative Effectiveness and 
Safety (EMPRISE) Study."  Circulation. 2019 Apr 8. doi: 
10.1161/CIRCULATIONAHA.118.039177
o         or while the subject is on at least one blood pressure–lowering treatment
Dispensing of at least one of the following medications in the 180 days prior to drug initiation:
ACE inhibitor
 Benazepril, captopril, enalapril, fosinopril, lisinopril, moexipril, perindopril, quinapril, ramipril, 
trandolapril
ARB  
Azilsartan, candesartan, eprosartan, irbesartan, losartan, olmesartan, telmisartan, valsartan
Beta blocker 
Acebutolol, atenolol, betaxolol, bisoprolol, carteolol, carvedilol, esmolol, labetalol, metoprolol tartrate, 
metoprolol succinate, propranolol, penbutolol, pindolol, nadolol, nebivolol, sotalol, timolol
Calcium channel blocker 
Diltiazem, mibefradil, verapamil, amlodipine, clevidipine, bepridil, felodipine, isradipine, nicardipine, 
nifedipine, nimodipine, nisoldipine
Loop diuretics 
Furosemide, bumetanide, torsemide, ethacrynic acid
Other diuretics 
Amiloride, eplerenone, spironolactone, triamterene
Other hypertension drugs 
Doxazosin, eplerenone, prazosin, terazosin, clonidine, guanabenz, guanadrel, guanethidine, guanfacine, 
hydralazine, methyldopa, metyrosine, reserpine, minoxidil, aliskiren 
Patorno, Elisabetta et al. "Cardiovascular outcomes associated with canagliflozin versus 
other non-gliflozin antidiabetic drugs: population based cohort study." BMJ 
2018;360:k119 http://dx.doi.org/10.1136/bmj.k119
Patorno, Elisabetta et al. "Empagliflozin and the Risk of Heart Failure Hospitalization in 
Routine Clinical Care: A First Analysis from the Empagliflozin Comparative Effectiveness and 
Safety (EMPRISE) Study."  Circulation. 2019 Apr 8. doi: 
10.1161/CIRCULATIONAHA.118.039177
2a
2b
Appendix A

o         or current daily cigarette smoker
Measured 180 days prior to drug initiation in any diagnosis/procedure position and inpatient or 
outpatient care setting-
ICD-9 Codes
V15.82 
305.1x 
984.84  
CPT codes 
99406, 99407, G0436, G0437, G9016, S9453, S4995, G9276, G9458, 1034F, 4004F, 4001F
 
OR dispensing of at least one nicotine or varenicline prescription: nicotine, varenicline
Desai, Rishi J et al. “Identification of smoking using Medicare data--a validation study of 
claims-based algorithms.” Pharmacoepidemiology and drug safety vol. 25,4 (2016): 472-5. 
doi:10.1002/pds.3953
o         or documented microalbuminuria or macroalbuminuria
Measured 180 days prior to drug initiation in any diagnosis/procedure position and inpatient or 
outpatient care setting -
Proteinuria  ICD 9 DX
791.0
ICD10 DX
R80.X
Albumin abnormality ICD9 Dx- 790.99
ICD10 Dx - R77.0 
o         or documented high-density lipoprotein (HDL) cholesterol of <1 mmol/l (<39 mg/dl).
N/A
Women must be:
– Postmenopausal, 
defined as >45 years of age with amenorrhea for at least 18 months, or
>45 years of age with amenorrhea for at least 6 months and less than 18 months and a
serum follicle stimulating hormone (FSH) level >40 IU/ml, 
Women Age >45 years at drug initiation  OR
– or Surgically sterile (have had a hysterectomy or bilateral oophorectomy, tubal ligation), or
otherwise be incapable of pregnancy, 
N/A
– or Heterosexually active and practicing a highly effective method of birth control, including
hormonal prescription oral contraceptives, contraceptive injections, contraceptive patch,
intrauterine device, double-barrier method (e.g., condoms, diaphragm, or cervical cap with
spermicidal foam, cream, or gel), or male partner sterilization, consistent with local
regulations regarding use of birth control methods for subjects participating in clinical
trials, for the duration of their participation in the study, 
Measured 180 days prior to drug initiation in any diagnosis position and inpatient or outpatient care 
setting-
Encounter for contraceptive management
ICD9: V25 
OR
Non-oral contraceptives (brand names)-
Depo-subQ
Provera 104
Depo-Provera, generic
Mirena
Ortho Evra
NuvaRing
Implanon
Oral contraceptives (generic names)-  See "oral contraceptives - generic" sheet.
Oral contraceptives (brand names)- See "oral contraceptives - generic" sheet.
Krumme, Alexis A, et. al. “Study protocol for the dabigatran, apixaban, rivaroxaban, 
edoxaban, warfarin comparative effectiveness research study.” J. Comp. Eff. Res. 
(2018):7(1), 57–66. doi: 10.2217/cer-2017-0053.
– or Not heterosexually active.
Note: subjects who are not heterosexually active at screening must agree to utilize a highly
effective method of birth control if they become heterosexually active during their
participation in the study.
N/A
4
Women of childbearing potential must have a negative urine β-human chorionic
gonadotropin (β-hCG) pregnancy test at screening and baseline (predose, Day 1).
N/A
One of the exclusion criteria is pregnancy, so this can be skipped.
5
Willing and able to adhere to the prohibitions and restrictions specified in this protocol.
N/A
6
Subjects must have signed an informed consent document indicating that they understand
the purpose of and procedures required for the study and are willing to participate in the
study.
N/A
7
To participate in the optional pharmacogenomic component of this study, subjects must
have signed the informed consent form for pharmacogenomic research indicating
willingness to participate in the pharmacogenomic component of the study (where local
regulations permit). Refusal to give consent for this component does not exclude a subject
from participation in the clinical study.
N/A
8
Subjects must have taken ≥80% of their single-blind placebo capsules during the 2-week
run-in period at Day 1 to be eligible for randomization.
N/A
1
History of diabetic ketoacidosis, type 1 diabetes, pancreas or beta-cell transplantation, or diabetes secondary to pancreatitis or 
pancreatectomy.
Measured 180 days prior to drug initiation in any diagnosis position and inpatient or outpatient care 
setting- DM type 1- At least 1 ICD-9 Dx code of 250.x1 or 250.x3 or ICD-10 Dx code of E10.x 
Measured 180 days prior to drug initiation in any procedure position and inpatient or outpatient care 
setting- 
Secondary diabetes ICD-9 procedure:
249.xx  Secondary diabetes
Measured 180 days prior to drug initiation in any diagnosis position and inpatient or outpatient care 
setting- 
Ketoacidosis
250.1x
Notes- We can't capture  pancreas or beta-cell transplantation in claims datasets.
Patorno, Elisabetta et al. "Cardiovascular outcomes associated with canagliflozin versus 
other non-gliflozin antidiabetic drugs: population based cohort study." BMJ 
2018;360:k119 http://dx.doi.org/10.1136/bmj.k119
Patorno, Elisabetta et al. "Empagliflozin and the Risk of Heart Failure Hospitalization in 
Routine Clinical Care: A First Analysis from the Empagliflozin Comparative Effectiveness and 
Safety (EMPRISE) Study."  Circulation. 2019 Apr 8. doi: 
10.1161/CIRCULATIONAHA.118.039177
2
On an AHA and not on a stable regimen (i.e., agents and doses) for at least 8 weeks before
the screening visit and through the screening/run-in period. Note: a stable dose of insulin
is defined as no change in the insulin regimen (i.e., type[s] of insulin) and ≤15% change in
the total daily dose of insulin (averaged over 1 week to account for day-to-day variability).
N/A
EXCLUSION CRITERIA
3
Appendix A

3
– For patients on a sulfonylurea agent or on insulin: fasting fingerstick glucose at site
<110 mg/dl (<6 mmol/l) at Baseline/Day 1.
Note: at the investigator’s discretion, based upon an assessment of recent self-monitored
blood glucose (SMBG) values, subjects meeting either of these fingerstick glucose exclusion
criteria may continue the single-blind placebo and return to the investigational site within
14 days and may be randomized if the repeat fasting fingerstick value no longer meets the
exclusion criterion. Subjects with fingerstick glucose >270 mg/dl (>15 mmol/l) may have
their AHA regimen adjusted and be rescreened once on a stable regimen for at least 8 weeks.
N/A
4
History of one or more severe hypoglycemic episode within 6 months before screening.
Note: a severe hypoglycemic episode is defined as an event that requires the help of
another person.
Measured 180 days prior to drug initiation in primary diagnosis position and inpatient care setting- 
ICD-9 diagnosis: 
251.0, 251.1x, 251.2x, or 250.8x. 
if identified by 250.8x are not included if they co-occur with one of the following diagnoses: 
259.8, 272.7, 681.xx, 682.xx, 686.9, 707.1x, 707.2x, 707.8, 707.9, 709.3, 730.0x, 730.1x, 730.2x, 
731.8. 
PPV 89% (ED component) -- Ginde AA, Blanc PG, Lieberman RM, Camargo CA, Jr. Validation 
of ICD-9-CM coding algorithm for improved identification of hypoglycemia visits. BMC 
endocrine disorders 2008;8:4.
PPV 78% (inpatient component) -- Schelleman H, Bilker WB, Brensinger CM, Wan F, 
Hennessy S. Anti-infectives and the risk of severe hypoglycemia in users of glipizide or 
glyburide. Clinical pharmacology and therapeutics 2010;88:214-22.
5
History of hereditary glucose-galactose malabsorption or primary renal glucosuria.
Measured 180 days prior to drug initiation in any diagnosis position and inpatient or outpatient care 
setting- 
ICD-9 diagnosis codes: 271.3x, 271.4x
Elisabetta suggested these codes
6
Ongoing, inadequately controlled thyroid disorder.
Note: subjects on thyroid hormone-replacement therapy must be on a stable dose for at
least 6 weeks before Day 1.
N/A
7
Renal disease that required treatment with immunosuppressive therapy or a history of
dialysis or renal transplant.
Note: subjects with a history of treated childhood renal disease, without sequelae, may
participate.
Measured 180 days prior to drug initiation - 
1. Acute renal diseases OR Chronic Renal Insufficiency in any diagnosis position and inpatient or 
outpatient care setting AND dispensing of an immunosuppressive agent:
Acute Renal Disease 572.4x, 580.xx, 584.xx, 791.2x, 791.3x
Chronic Renal Insufficiency 582.xx, 583.xx, 585.xx, 586.xx, 587.xx
Immunosuppressive therapy:
 HCPCS codes- “36514”, “80420”, “C9256”, “J0702”, “J0704”, “J1020”, “J1030”, “J1040”, “J1094”, 
“J1095”, “J1100”, “J1690”, “J1700”, “J1710”, “J1720”, “J2640”, “J2650”, “J2920”, “J2930”, “J3300”, 
“J3301”, “J3302”, “J3303”, “J7312”, “J7506”, “J7509”, “J7510”, “J7624”, “J7637”, “J7638”, “J7683”, 
“J7684”, “J8540”, “K0512”, “K0513”, “K0528”, “S0173”
with 
immunosuppressive agents in next tab "immunosuppressive agents"
OR
2. Dialysis in any diagnosis position and inpatient care setting OR Renal transplant in any diagnosis 
position and inpatient or outpatient care setting 
Codes are in the sheet 'Dialysis and Renal Transplant'
Patorno, Elisabetta et al. "Cardiovascular outcomes associated with canagliflozin versus 
other non-gliflozin antidiabetic drugs: population based cohort study." BMJ 
2018;360:k119 http://dx.doi.org/10.1136/bmj.k119
Patorno, Elisabetta et al. "Empagliflozin and the Risk of Heart Failure Hospitalization in 
Routine Clinical Care: A First Analysis from the Empagliflozin Comparative Effectiveness and 
Safety (EMPRISE) Study."  Circulation. 2019 Apr 8. doi: 
10.1161/CIRCULATIONAHA.118.039177
8
MI, unstable angina, revascularization procedure, or cerebrovascular accident within 3
months before screening, or a planned revascularization procedure, or history of New York
Heart Association (NYHA) Class IV cardiac disease.
Measured 90 days  prior to drug initiation in any diagnosis/procedure position and care setting defined 
below- 
Any of the following codes in inpatient or outpatient care setting: 
MI  ICD-9  diagnosis 410.xx 
Unstable angina  ICD-9  diagnosis 411.xx 
Left ventricular assist- CPT-4 33990-33993
Stroke ICD-9 diagnosis: 430.xx, 431.xx, 433.x1, 434.x1, 436.x  
Carotid bypass: ICD9 procedure: 39.28
TIA 435.xx
Peripheral arterial stenting or surgical revascularization ICD-9 39.25, 39.50, 39.99. 
PTCA:
Inpatient CPT-4: 92973, 92982, 92984, 92995, 92996, 92920 – 92921, 92924 – 92925, 92937, 92938, 
92941, 92943, 92944
OR –
Inpatient or outpatient - ICD-9 procedure: 00.66, 36.01, 36.02, 36.03, 36.05, 36.09
Stenting:
Inpatient CPT-4:  92980, 92981, 92928 – 92929, 92933 - 92934 – OR – Inpatient or outpatient - ICD-9 
procedure: 36.06, 36.07
CABG: Inpatient CPT-4: 33510 – 33536, 33545, 33572 – OR – Inpatient or outpatient - ICD-9 procedure: 
36.1x, 36.2x
Transmyocardial revascularization: Inpatient or Outpatient CPT-4: 33140, 33141 OR - Inpatient or 
outpatient ICD-9 procedure: 36.31-36.34
Patorno, Elisabetta et al. "Cardiovascular outcomes associated with canagliflozin versus 
other non-gliflozin antidiabetic drugs: population based cohort study." BMJ 
2018;360:k119 http://dx.doi.org/10.1136/bmj.k119
Patorno, Elisabetta et al. "Empagliflozin and the Risk of Heart Failure Hospitalization in 
Routine Clinical Care: A First Analysis from the Empagliflozin Comparative Effectiveness and 
Safety (EMPRISE) Study."  Circulation. 2019 Apr 8. doi: 
10.1161/CIRCULATIONAHA.118.039177
Left Ventricular Assist Codes from- http://www.hcpro.com/HIM-289708-859/Tip-Note-
new-codes-for-ventricular-assist-devices.html 
9
Findings on 12-lead electrocardiogram (ECG) that would require urgent diagnostic
evaluation or intervention (e.g., new clinically important arrhythmia or conduction
disturbance).
Measured 180 days  prior to drug initiation in primary diagnosis position and inpatient care setting- 
Cardiac conduction disorders ICD 9: 426.xx
Other cardiac dysrhythmia ICD 9: 427.xx, exclude 427.5x (cardiac arrest) and 427.3x
And, 427.6x
Patorno, Elisabetta et al. "Cardiovascular outcomes associated with canagliflozin versus 
other non-gliflozin antidiabetic drugs: population based cohort study." BMJ 
2018;360:k119 http://dx.doi.org/10.1136/bmj.k119
Patorno, Elisabetta et al. "Empagliflozin and the Risk of Heart Failure Hospitalization in 
Routine Clinical Care: A First Analysis from the Empagliflozin Comparative Effectiveness and 
Safety (EMPRISE) Study."  Circulation. 2019 Apr 8. doi: 
10.1161/CIRCULATIONAHA.118.039177
Appendix A

10
History of hepatitis B surface antigen or hepatitis C antibody positive (unless associated
with documented persistently stable/normal range aspartate aminotransferase [AST] and
alanine aminotransferase [ALT] levels), or other clinically active liver disease.
Measured 180 days  prior to drug initiation in any diagnosis/procedure position and inpatient or 
outpatient care setting- 
Liver disease- ICD-9 diagnosis:
070.xx, 570.xx- 573.xx 
456.0x-456.2x, 576.8x, 782.4x, 789.5x 
ICD-9 procedure codes:
39.1x, 42.91 
Patorno, Elisabetta et al. "Cardiovascular outcomes associated with canagliflozin versus 
other non-gliflozin antidiabetic drugs: population based cohort study." BMJ 
2018;360:k119 http://dx.doi.org/10.1136/bmj.k119
Patorno, Elisabetta et al. "Empagliflozin and the Risk of Heart Failure Hospitalization in 
Routine Clinical Care: A First Analysis from the Empagliflozin Comparative Effectiveness and 
Safety (EMPRISE) Study."  Circulation. 2019 Apr 8. doi: 
10.1161/CIRCULATIONAHA.118.039177
11
Any history of or planned bariatric surgery.
Measured 1825 days  prior to drug initiation in any procedure position and inpatient or outpatient care 
setting- 
CPT -Code- Abbreviation Procedure
43644 -LRYBG -Laparoscopic Roux-en-Y gastric bypass (Roux limb 150 cm or less)
43645 -LRYGBX-
Laparoscopic gastric bypass with small intestine reconstruction to
limit absorption
43770 -LAGB- Laparoscopic adjustable gastric band
43846 -ORYGB- Open Roux-en-Y gastric bypass (Roux limb 150 cm or less)
43847 -ORYGBX- Open gastric bypass with small intestine reconstruction to limit
absorption
Hatoam, Ida J et al. "Clinical Factors Associated With Remission of Obesity-Related 
Comorbidities After Bariatric Surgery." JAMA Surg. 2016;151(2):130-137. 
doi:10.1001/jamasurg.2015.3231
12
Estimated glomerular filtration rate (eGFR) <30 ml/min/1.73 m2 at screening (provided by
the central laboratory)
– For subjects taking metformin: at screening, serum creatinine ≥1.4 mg/dl (124 μmol/l) for
men or ≥1.3 mg/dl (115 μmol/l) for women; no contraindication to the use of metformin
(including eGFR) based on the label of the country of investigational site
N/A
13
ALT levels >2.0 times the upper limit of normal (ULN) or total bilirubin >1.5 times the ULN
at screening, unless in the opinion of the investigator and as agreed upon by the sponsor’s
medical officer, the findings are consistent with Gilbert’s disease.
N/A
14
History of malignancy within 5 years before screening (exceptions: squamous and basal cell
carcinomas of the skin and carcinoma of the cervix in situ, or a malignancy that in the
opinion of the investigator, with concurrence with the sponsor’s medical monitor, is
considered cured with minimal risk of recurrence).
Measured 1825 days  prior to drug initiation in any diagnosis position and inpatient or outpatient care 
setting- 
History of malignant neoplasm 140.xx-208.xx (except 173.xx, non-melanoma skin cancer)
Patorno, Elisabetta et al. "Cardiovascular outcomes associated with canagliflozin versus 
other non-gliflozin antidiabetic drugs: population based cohort study." BMJ 
2018;360:k119 http://dx.doi.org/10.1136/bmj.k119
Patorno, Elisabetta et al. "Empagliflozin and the Risk of Heart Failure Hospitalization in 
Routine Clinical Care: A First Analysis from the Empagliflozin Comparative Effectiveness and 
Safety (EMPRISE) Study."  Circulation. 2019 Apr 8. doi: 
10.1161/CIRCULATIONAHA.118.039177
15
History of human immunodeficiency virus (HIV) antibody positive.
Measured 1825 days  prior to drug initiation in any diagnosis position and inpatient or outpatient care 
setting- 
042 Human immunodeficiency virus [HIV] disease
079.53 Human immunodeficiency virus, type 2 [HIV-2]
V08 Asymptomatic human immunodeficiency virus [HIV] infection status
OR filled prescription for HIV treatment:
(Please see HIV Treatment sheet)
Patorno, Elisabetta et al. "Cardiovascular outcomes associated with canagliflozin versus 
other non-gliflozin antidiabetic drugs: population based cohort study." BMJ 
2018;360:k119 http://dx.doi.org/10.1136/bmj.k119
Patorno, Elisabetta et al. "Empagliflozin and the Risk of Heart Failure Hospitalization in 
Routine Clinical Care: A First Analysis from the Empagliflozin Comparative Effectiveness and 
Safety (EMPRISE) Study."  Circulation. 2019 Apr 8. doi: 
10.1161/CIRCULATIONAHA.118.039177
16
Subject has a current clinically important hematological disorder (e.g., symptomatic
anemia, proliferative bone marrow disorder, thrombocytopenia).
Measured 180 days  prior to drug initiation in any diagnosis position and inpatient or outpatient care 
setting- 
ICD-9 Diagnosis Codes: 238.4x, 289.83, 238.71, 280.x-285.x, 287.3x, 287.4x, 287.5x
Expert in this study area advised on the codes used for this inclusion/exclusion criteria.
17
Investigator’s assessment that the subject’s life expectancy is less than 1 year, or any
condition that in the opinion of the investigator would make participation not in the best
interest of the subject, or could prevent, limit, or confound the protocol-specified safety or
efficacy assessments.
Measured 180 days prior to drug initiation- 
CCI >=10
Gagne, Josh J et. al. "A combined comorbidity score predicted mortality in elderly patients 
better than existing scores." J Clin Epidemiol. 2011 Jul;64(7):749-59. doi: 
10.1016/j.jclinepi.2010.10.004.
Sun, Jenny W et. al. "Validation of the Combined Comorbidity Index of Charlson and 
Elixhauser to Predict 30-Day Mortality Across ICD-9 and ICD-10." Med Care. 2018 
Sep;56(9):812. doi: 10.1097/MLR.0000000000000954.
18
Major surgery (i.e., requiring general anesthesia) within 3 months of the screening visit or
any surgery planned during the subject’s expected participation in the study (except minor
surgery; i.e., outpatient surgery under local anesthesia).
Measured 90 days  prior to drug initiation in any diagnosis position and inpatient or outpatient care 
setting- 
Major surgery selected from codes range 35.x- 84.x 
19
Any condition that, in the opinion of the investigator, would compromise the well-being of
the subject or prevent the subject from meeting or performing study requirements.
N/A
20
Current use of other sodium glucose co-transporter 2 (SGLT2) inhibitor.
Measured 180 days prior to drug initiation as a dispensing of one of the following drugs- 
empagliflozin, dapagliflozin, ertugliflozin
21
Known allergies, hypersensitivity, or intolerance to canagliflozin or its excipients.
N/A
22
Current use of a corticosteroid medication or immunosuppressive agent, or likely to require
treatment with a corticosteroid medication (for longer than 2 weeks in duration) or an
immunosuppressive agent. Note: subjects using inhaled, intranasal, intra-articular, or
topical corticosteroids, or corticosteroids in therapeutic replacement doses may
participate.
Measured 180 days prior to drug initiation as a dispensing of one of the following drugs- 
Systemic corticosteroids (With Route of Administration is intravenous):-  Cortisone, hydrocortisone, 
prednisone, prednisolone, methylprednisolone, triamcinolone, dexamethasone, betamethasone. 
immunosuppressive agents 
o RA, AS, and PsA: methotrexate, hydroxychloroquine, azathioprine,
cyclosporine, leflunomide, minocycline, sulfasalazine.
o SLE: hydroxychloroquine, azathioprine, mycophenolate mofetil.
o IBD: azathioprine, mercaptopurine
Patorno, Elisabetta et al. "Cardiovascular outcomes associated with canagliflozin versus 
other non-gliflozin antidiabetic drugs: population based cohort study." BMJ 
2018;360:k119 http://dx.doi.org/10.1136/bmj.k119
Patorno, Elisabetta et al. "Empagliflozin and the Risk of Heart Failure Hospitalization in 
Routine Clinical Care: A First Analysis from the Empagliflozin Comparative Effectiveness and 
Safety (EMPRISE) Study."  Circulation. 2019 Apr 8. doi: 
10.1161/CIRCULATIONAHA.118.039177
 
Desai, Rishi et. al. "Risk of serious infections associated with use of immunosuppressive 
agents in pregnant women with autoimmune inflammatory conditions: cohort study" BMJ 
2017; 356 doi: https://doi.org/10.1136/bmj.j895 
23
Received an active investigational drug (including vaccines) or used an investigational
medical device within 3 months before Day 1/baseline or received at least one dose of
canagliflozin in a prior study.
Already applied based on the canagliflozin and comparator washout, but measured again 90 days prior to 
drug initiation as a dispensing for canagliflozin
Appendix A

24
History of drug or alcohol abuse within 3 years before screening.
Measured 1095 days prior to drug initiation in any diagnosis position and inpatient or outpatient care 
setting- 
Alcohol abuse or dependence 291.xx, 303.xx, 305.0x, 571.0x, 571.1x, 571.2x, 571.3x, 357.5x, 425.5x, 
E860.0x, V11.3x
Drug abuse or dependence 292.xx, 304.xx, 305.2x-305.9x, 648.3x
Patorno, Elisabetta et al. "Cardiovascular outcomes associated with canagliflozin versus 
other non-gliflozin antidiabetic drugs: population based cohort study." BMJ 
2018;360:k119 http://dx.doi.org/10.1136/bmj.k119
Patorno, Elisabetta et al. "Empagliflozin and the Risk of Heart Failure Hospitalization in 
Routine Clinical Care: A First Analysis from the Empagliflozin Comparative Effectiveness and 
Safety (EMPRISE) Study."  Circulation. 2019 Apr 8. doi: 
10.1161/CIRCULATIONAHA.118.039177
25
Pregnant or breastfeeding or planning to become pregnant or breastfeed during the study.
Measured 180 days prior to drug initiation in any diagnosis position and inpatient or outpatient care 
setting- 
(Please see Pregnancy Sheet for code list)
26
Employees of the investigator or study center, with direct involvement in the proposed
study or other studies under the direction of that investigator or study center, as well as
family members of the employees or the investigator.
N/A
Appendix A

Trial ID 
sNDA22
Trial Name (with web links)
CANVAS
NCT
NCT01032629
Trial category
Secondary indication
Therapeutic Area
Endocrinology
RCT Category  
4a- Unintended S with label change
Brand Name
Invokana 
Generic Name
Canagliflozin 
Sponsor
Janssen Research & Development, LLC
Year
2017
Measurable endpoint
Major Adverse Cardiovascular Events, Including CV Death, Nonfatal Myocardial 
Infarction (MI), and Nonfatal Stroke
Exposure
Canaglifloziin
Comparator
Placebo
Population
50% on insulin, 47% using Sulfonylurea, 73% Metformin, 72% statin
Trial finding
HR = 0.86 (95% CI 0.75–0.97)
No. of Patients
4330
Non-inferiority margin
HR = 1.3
Assay Sens. Endpoint
Assay Sens. Finding
Power
0.90. With 688 cardiovascular safety events recorded across the 
trials, there would be at least 90% power, at an alpha level of 0.05, to 
exclude an upper margin of the 95% confidence interval for the 
hazard ratio of 1.3. 
Blinding
Statistical Method
Cardiovascular safety was to be shown if the upper boundary of the 95% 
confidence interval of the hazard ratio with canagliflozin as compared with 
placebo was less than 1.3, and superiority was to be shown if the upper 
boundary was less than 1.0.
Appendix A

Mortality- Dependent on data source. 
1. All-cause mortality / inpatient mortality
Identified using the vital status file-
Medicare
Identified using the discharge status codes-
Optum-
• 20 = EXPIRED
• 21 = EXPIRED TO BE DEFINED AT STATE LEVEL
• 22 = EXPIRED TO BE DEFINED AT STATE LEVEL
• 23 = EXPIRED TO BE DEFINED AT STATE LEVEL
• 24 = EXPIRED TO BE DEFINED AT STATE LEVEL
• 25 = EXPIRED TO BE DEFINED AT STATE LEVEL
• 26 = EXPIRED TO BE DEFINED AT STATE LEVEL
• 27 = EXPIRED TO BE DEFINED AT STATE LEVEL
• 28 = EXPIRED TO BE DEFINED AT STATE LEVEL
• 29 = EXPIRED TO BE DEFINED AT STATE LEVEL
• 40 = EXPIRED AT HOME (HOSPICE)
• 41 = EXPIRED IN A MEDICAL FACILITY (HOSPICE)
• 42 = EXPIRED - PLACE UNKNOWN (HOSPICE)
Truven-
• 20 - Died
• 22 - Died
• 23 - Died
• 24 - Died
• 25 - Died
• 26 - Died
• 27 - Died
• 28 - Died
• 29 - Died
• 40 - Other died status or Expired at home (Hospice claims only) (depends on year)
Appendix A

• 41 - Other died status or Expired in medical facility (Hospice claims only) (depends on year)
• 42 - Other died status or Expired - place unknown (Hospice claims only) (depends on year)
• 21 - Died or Disch./Transf. to court/law enforcement (depends on year)
2. CV mortality
Information on CV mortality through data linkage with the National Death Index (NDI) will be available for Medicare 
at a later date. We will conduct secondary analyses using CV mortality at that time.
Appendix A

drug_class
Brand Name
oral contraceptive
Apri;
oral contraceptive
Desogen;
oral contraceptive
Ortho-Cept;
oral contraceptive
Reclipsen
oral contraceptive
Kariva;
oral contraceptive
Mircette
oral contraceptive
Cyclessa;
oral contraceptive
Velivet
oral contraceptive
Yasmin
oral contraceptive
Yaz
oral contraceptive
Demulen 1/35;
oral contraceptive
Kelnor;
oral contraceptive
Zovia 1/25
oral contraceptive
Demulen 1/50;
oral contraceptive
Zovia 1/50
oral contraceptive
Alesse;
oral contraceptive
Aviane;
oral contraceptive
Lessina;
oral contraceptive
Lutera
oral contraceptive
Nordette;
oral contraceptive
Portia;
oral contraceptive
Levora
oral contraceptive
Lybrel
oral contraceptive
Seasonale;
oral contraceptive
Quasense;
oral contraceptive
Jolessa
oral contraceptive
Seasonique
oral contraceptive
Empresse;
oral contraceptive
Triphasil;
oral contraceptive
Trivora
oral contraceptive
Ovcon 35 
oral contraceptive
Balziva;
Appendix A

oral contraceptive
Femcon Fe
oral contraceptive
Brevicon;
oral contraceptive
Nortrel 0.5/35;
oral contraceptive
Modicon;
oral contraceptive
Necon 0.5/35
oral contraceptive
Norinyl 1/35;
oral contraceptive
Nortrel 1/35;
oral contraceptive
Ortho-Novum 1/35;
oral contraceptive
Necon 1/35
oral contraceptive
Ovcon 50;
oral contraceptive
Necon 1/50
oral contraceptive
Ortho-Novum 10/11
oral contraceptive
Aranelle;
oral contraceptive
Tri-Norinyl
oral contraceptive
Ortho-Novum 7/7/7;
oral contraceptive
Necon
oral contraceptive
Micronor;
oral contraceptive
Nor-QD;
oral contraceptive
Camila;
oral contraceptive
Errin;
oral contraceptive
Jolivette
oral contraceptive
Junel 21 1/20;
oral contraceptive
Junel 21 Fe 1/20;
oral contraceptive
Loestrin 21 1/20;
oral contraceptive
Loestrin 21 Fe 1/20;
oral contraceptive
Loestrin 24 Fe;
oral contraceptive
Microgestin 1/20
oral contraceptive
Microgestin Fe 1/20
oral contraceptive
Junel 21 1.5/30;
oral contraceptive
Junel 21 Fe 1.5/30;
oral contraceptive
Loestrin 1.5/30;
oral contraceptive
Loestrin Fe 1.5/30
oral contraceptive
Microgestin 1.5/30
Appendix A

oral contraceptive
Microgestin Fe 1.5/30
oral contraceptive
Estrostep Fe;
oral contraceptive
Tilia Fe;
oral contraceptive
TriLegest Fe
oral contraceptive
Ortho-Cyclen;
oral contraceptive
Sprintec;
oral contraceptive
MonoNessa;
oral contraceptive
Previfem
oral contraceptive
Ortho Tri-Cyclen Lo;
oral contraceptive
Tri-Previfem;
oral contraceptive
TriNessa
oral contraceptive
Ortho Tri-Cyclen;
oral contraceptive
Tri-Sprintec
oral contraceptive
Cryselle;
oral contraceptive
Lo/Ovral;
oral contraceptive
Low-Ogestrel
oral contraceptive
Ovral;
oral contraceptive
Ogestrel
oral contraceptive
Zovia 1/50
oral contraceptive
Alesse;
oral contraceptive
Aviane;
oral contraceptive
Lessina;
oral contraceptive
Lutera
oral contraceptive
Nordette;
oral contraceptive
Portia;
oral contraceptive
Levora
oral contraceptive
Lybrel
oral contraceptive
Seasonale;
oral contraceptive
Quasense;
oral contraceptive
Jolessa
oral contraceptive
Seasonique
oral contraceptive
Empresse;
oral contraceptive
Triphasil;
Appendix A

oral contraceptive
Trivora
oral contraceptive
Ovcon 35 
oral contraceptive
Balziva;
oral contraceptive
Femcon Fe
oral contraceptive
Brevicon;
oral contraceptive
Nortrel 0.5/35;
oral contraceptive
Modicon;
oral contraceptive
Necon 0.5/35
oral contraceptive
Norinyl 1/35;
oral contraceptive
Nortrel 1/35;
oral contraceptive
Ortho-Novum 1/35;
oral contraceptive
Necon 1/35
oral contraceptive
Ovcon 50;
oral contraceptive
Necon 1/50
oral contraceptive
Ortho-Novum 10/11
oral contraceptive
Aranelle;
oral contraceptive
Tri-Norinyl
oral contraceptive
Ortho-Novum 7/7/7;
oral contraceptive
Necon
oral contraceptive
Micronor;
oral contraceptive
Nor-QD;
oral contraceptive
Camila;
oral contraceptive
Errin;
oral contraceptive
Jolivette
oral contraceptive
Junel 21 1/20;
oral contraceptive
Junel 21 Fe 1/20;
oral contraceptive
Loestrin 21 1/20;
oral contraceptive
Loestrin 21 Fe 1/20;
oral contraceptive
Loestrin 24 Fe;
oral contraceptive
Microgestin 1/20
oral contraceptive
Microgestin Fe 1/20
oral contraceptive
Junel 21 1.5/30;
oral contraceptive
Junel 21 Fe 1.5/30;
Appendix A

oral contraceptive
Loestrin 1.5/30;
oral contraceptive
Loestrin Fe 1.5/30
oral contraceptive
Microgestin 1.5/30
oral contraceptive
Microgestin Fe 1.5/30
oral contraceptive
Estrostep Fe;
oral contraceptive
Tilia Fe;
oral contraceptive
TriLegest Fe
oral contraceptive
Ortho-Cyclen;
oral contraceptive
Sprintec;
oral contraceptive
MonoNessa;
oral contraceptive
Previfem
oral contraceptive
Ortho Tri-Cyclen Lo;
oral contraceptive
Tri-Previfem;
oral contraceptive
TriNessa
oral contraceptive
Ortho Tri-Cyclen;
oral contraceptive
Tri-Sprintec
oral contraceptive
Cryselle;
oral contraceptive
Lo/Ovral;
oral contraceptive
Low-Ogestrel
oral contraceptive
Ovral;
oral contraceptive
Ogestrel
Appendix A

drug_class
generic
generic_ndc
oral contraceptive
estradiol
desogestrel-ethinyl estradiol
oral contraceptive
estradiol
desogestrel-ethinyl estradiol/ethinyl estradiol
oral contraceptive
estradiol
drospirenone/estradiol
oral contraceptive
estradiol
drospirenone/ethinyl estradiol/levomefolate calcium
oral contraceptive
estradiol
estradiol
oral contraceptive
estradiol
estradiol acetate
oral contraceptive
estradiol
estradiol benzoate
oral contraceptive
estradiol
estradiol cypionate
oral contraceptive
estradiol
estradiol cypionate/medroxyprogesterone acet
oral contraceptive
estradiol
estradiol hemihydrate, micronized
oral contraceptive
estradiol
estradiol micronized
oral contraceptive
estradiol
estradiol valerate
oral contraceptive
estradiol
estradiol valerate/dienogest
oral contraceptive
estradiol
estradiol valerate/sesame oil
oral contraceptive
estradiol
estradiol/estrone
oral contraceptive
estradiol
estradiol/estrone/vit b12
oral contraceptive
estradiol
estradiol/levonorgestrel
oral contraceptive
estradiol
estradiol/norethindrone acetate
oral contraceptive
estradiol
estradiol/norgestimate
oral contraceptive
estradiol
estradiol/progesterone
oral contraceptive
estradiol
ethinyl estradiol
oral contraceptive
estradiol
ethinyl estradiol/drospirenone
oral contraceptive
estradiol
ethinyl estradiol/norethindrone acetate
oral contraceptive
estradiol
ethynodiol d-ethinyl estradiol
oral contraceptive
estradiol
ethynodiol diacetate-ethinyl estradiol
oral contraceptive
estradiol
etonogestrel/ethinyl estradiol
oral contraceptive
estradiol
levonorgestrel-ethinyl estradiol
oral contraceptive
estradiol
levonorgestrel/ethinyl estradiol and ethinyl estradiol
oral contraceptive
estradiol
me-testosterone/eth estradiol
oral contraceptive
estradiol
metttrn/estradiol/multivits
oral contraceptive
estradiol
norelgestromin/ethinyl estradiol
oral contraceptive
estradiol
norethindrone a-e estradiol
oral contraceptive
estradiol
norethindrone a-e estradiol/fe
Appendix A

oral contraceptive
estradiol
norethindrone a-e estradiol/ferrous fumarate
oral contraceptive
estradiol
norethindrone acetate-ethinyl estradiol
oral contraceptive
estradiol
norethindrone acetate-ethinyl estradiol/ferrous fumarate
oral contraceptive
estradiol
norethindrone-ethin estradiol
oral contraceptive
estradiol
norethindrone-ethinyl estradiol
oral contraceptive
estradiol
norethindrone-ethinyl estradiol/ferrous fumarate
oral contraceptive
estradiol
norgestimate-ethinyl estradiol
oral contraceptive
estradiol
norgestrel-ethinyl estradiol
oral contraceptive
estradiol
testosterone cypionate/estradiol cypionate
oral contraceptive
estradiol
testosterone enanthate/estradiol valerate
oral contraceptive
estradiol
testosterone/estradiol
oral contraceptive
levonorgestrel
estradiol/levonorgestrel
oral contraceptive
levonorgestrel
levonorgestrel
oral contraceptive
levonorgestrel
levonorgestrel-eth estra
oral contraceptive
levonorgestrel
levonorgestrel-eth estra/pregnancy test kit
oral contraceptive
levonorgestrel
levonorgestrel-ethinyl estradiol
oral contraceptive
levonorgestrel
levonorgestrel/ethinyl estradiol and ethinyl estradiol
oral contraceptive
norethindrone
estradiol/norethindrone acetate
oral contraceptive
norethindrone
ethinyl estradiol/norethindrone acetate
oral contraceptive
norethindrone
leuprolide acetate/norethindrone acetate
oral contraceptive
norethindrone
norethindrone
oral contraceptive
norethindrone
norethindrone a-e estradiol
oral contraceptive
norethindrone
norethindrone a-e estradiol/fe
oral contraceptive
norethindrone
norethindrone a-e estradiol/ferrous fumarate
oral contraceptive
norethindrone
norethindrone acetate
oral contraceptive
norethindrone
norethindrone acetate-ethinyl estradiol
oral contraceptive
norethindrone
norethindrone acetate-ethinyl estradiol/ferrous fumarate
oral contraceptive
norethindrone
norethindrone-ethin estradiol
oral contraceptive
norethindrone
norethindrone-ethinyl estrad
oral contraceptive
norethindrone
norethindrone-ethinyl estradiol
oral contraceptive
norethindrone
norethindrone-ethinyl estradiol/ferrous fumarate
oral contraceptive
norethindrone
norethindrone-mestranol
Appendix A

oral contraceptive
norgestrel
norgestrel
oral contraceptive
norgestrel
norgestrel-ethinyl estradiol
oral contraceptive
polyestradiol phosphate
polyestradiol phosphate
Appendix A

Antidiabetic class
Specific agent
Notes
Canagliflozin
Approved 3/29/2013
Dapagliflozin
Empagliflozin
Ertugliflozin
Approved Dec 21, 2017
Glimepiride
Glipizide
Glyburide 
Alogliptin
Linagliptin
Saxagliptin
Sitagliptin
Exenatide
Liraglutide
Albiglutide
Approved April 15, 2014 and 
discontinued July 26, 2017
Dulaglutide
Approved Sep 18, 2014
Lixisenatide
Approved July 28, 2016
Semaglutide
Approved Dec 5, 2017
Insulin Aspart
Insulin Aspart/Insulin Aspart Protamine
Insulin Degludec
Insulin Detemir
Insulin Glargine
Insulin Glulisine
Insulin human isophane (NPH)
Insulin human regular (search with NPH, 
don't want bf-pk)
Insulin human regular/ Insulin human 
isophane (NPH)
Insulin Lispro
Insulin Lispro/Insulin Lispro Protamine
Pioglitazone
SGLT2-inhibitors
2nd generation sulfonylureas
DPP-4 inhibitors
GLP-1 receptor agonist (GLP1-RA)
Insulin
Glitazones
Appendix A

Rosiglitazone
Nateglinide
Repaglinide
Acarbose
Miglitol
Pramlintide
Pramlintide
Acetohexamide
Chlorpropamide
Tolazamide 
Tolbutamide
Meglitinides
Alpha-glucosidase inhibitors
1st generation sulfonylureas
Glitazones
Appendix A

Immunosuppressive agents
ALEMTUZUMAB
BETAMETHASONE
BETAMETHASONE ACETATE/BETAMETHASONE SODIUM PHOSPHATE
BETAMETHASONE DIPROPIONATE
BETAMETHASONE DIPROPIONATE/PROPYLENE GLYCOL
BETAMETHASONE SODIUM PHOSPHATE
BETAMETHASONE VALERATE
BUDESONIDE
BUDESONIDE, MICRONIZED
CORTISONE ACETATE
DEXAMETHASONE
DEXAMETHASONE ACETATE
DEXAMETHASONE ACETATE, MICRONIZED
DEXAMETHASONE ISONICOTINATE
DEXAMETHASONE PHOSPHATE
DEXAMETHASONE SOD PHOSPHATE
DEXAMETHASONE SODIUM PHOSPHATE IN 0.9 % SODIUM CHLORIDE
DEXAMETHASONE SODIUM PHOSPHATE/PF
DEXAMETHASONE, MICRONIZED
HYDROCORTISONE
HYDROCORTISONE ACETATE
HYDROCORTISONE CYPIONATE
HYDROCORTISONE SOD PHOSPHATE
HYDROCORTISONE SOD SUCCINATE
IMMUNE GLOBULIN,BOVINE/PLASMA PROTEIN FRACTION, BOVINE
IMMUNE GLOBULIN,GAMM(IGG)/GLYCINE/GLUCOSE/IGA 0 TO 50 MCG/ML
IMMUNE GLOBULIN,GAMM(IGG)/GLYCINE/IGA GREATER THAN 50 MCG/ML
IMMUNE GLOBULIN,GAMM(IGG)/MALTOSE/IGA GREATER THAN 50 MCG/ML
IMMUNE GLOBULIN,GAMM(IGG)/SORBITOL/GLYCIN/IGA 0 TO 50 MCG/ML
IMMUNE GLOBULIN,GAMM(IGG)/SUCROSE/IGA GREATER THAN 50 MCG/ML
IMMUNE GLOBULIN,GAMMA (IGG)/GLYCINE/IGA 0 TO 50 MCG/ML
IMMUNE GLOBULIN,GAMMA (IGG)/PROLINE/IGA 0 TO 50 MCG/ML
IMMUNE GLOBULIN GAMMA (IGG)/SORBITOL/IGA 0 TO 50 MCG/ML
Appendix A

IMMUNE GLOBULIN,GAMMA (IGG)/SORBITOL/IGA 0 TO 50 MCG/ML
LYMPHOCYTE IG,ANTITHYMOCYTE/THIMEROSAL
LYMPHOCYTE IMMUNE GLOBULIN,ANTITHYMOCYTE (EQUINE)
METHYLPREDNISOLONE
METHYLPREDNISOLONE ACETATE
METHYLPREDNISOLONE ACETATE, MICRONIZED
METHYLPREDNISOLONE SODIUM SUCCINATE
METHYLPREDNISOLONE SODIUM SUCCINATE/PF
METHYLPREDNISOLONE, MICRONIZED
PREDNISOLONE
PREDNISOLONE ACETATE
PREDNISOLONE ACETATE, MICRONIZED
PREDNISOLONE SOD PHOSPHATE
PREDNISOLONE, MICRONIZED
PREDNISONE
PREDNISONE MICRONIZED
RITUXIMAB
RITUXIMAB/HYALURONIDASE, HUMAN RECOMBINANT
TRIAMCINOLONE
TRIAMCINOLONE DIACETATE
TRIAMCINOLONE HEXACETONIDE
TRIAMCINOLONE HEXACETONIDE, MICRONIZED
AZATHIOPRINE
AZATHIOPRINE SODIUM
CYCLOSPORINE
CYCLOSPORINE, MODIFIED
HYDROXYCHLOROQUINE SULFATE
LEFLUNOMIDE
MERCAPTOPURINE
MINOCYCLINE HCL
MINOCYCLINE HCL MICROSPHERES
MINOCYCLINE HCL/EMOL COMB NO.16/SKIN CLNSR L4/TOP AGENT NO.3
MINOCYCLINE HCL/EYELID CLEANSER COMBINATION NO. 1
MINOCYCLINE HCL/WIPES WITH SKIN CLEANSER NO.4
MYCOPHENOLATE MOFETIL
MYCOPHENOLATE MOFETIL HCL
Appendix A

MYCOPHENOLATE MOFETIL HCL
SULFASALAZINE
Appendix A

HIV Treatment
Abacavir 
Amprenavir 
Atazanavir 
Darunavir 
Delavirdine 
Didanosine
Efavirenz 
Emtricitabine 
Enfuvirtide 
Etravirine 
Fosamprenavir 
Indinavir 
Lamivudine-Zidovudine
Maraviroc 
Nelfinavir 
Nevirapine 
Raltegravir 
Rilpivirine 
Ritonavir 
Ritonavir-Lopinavir 
Saquinavir
Stavudine
Tipranavir 
Zalcitabine 
Zidovudine
Appendix A

Pregnancy 
Dx codes 
650   NORMAL DELIVERY
660   OBSTRUCTED LABOR
661   ABNORMALITY OF FORCES OF LABOR
662   LONG LABOR
663   UMBILICAL CORD COMPLICATIONS DURING LABOR AND DELIVERY
664   TRAUMA TO PERINEUM AND VULVA DURING DELIVERY
665   OTHER OBSTETRICAL TRAUMA
667   RETAINED PLACENTA OR MEMBRANES WITHOUT HEMORRHAGE
668   COMPLICATIONS OF THE ADMINISTRATION OF ANESTHETIC OR OTHER SEDATION IN LABOR AND DELIVERY
669.94   UNSPECIFIED COMPLICATION OF LABOR AND DELIVERY POSTPARTUM CONDITION OR COMPLICATION
V24   POSTPARTUM CARE AND EXAMINATION
V24.0   POSTPARTUM CARE AND EXAMINATION IMMEDIATELY AFTER DELIVERY
V24.1   POSTPARTUM CARE AND EXAMINATION OF LACTATING MOTHER
V24.2   ROUTINE POSTPARTUM FOLLOW
V27   OUTCOME OF DELIVERY
V27.0   MOTHER WITH SINGLE LIVEBORN
V27.1   MOTHER WITH SINGLE STILLBORN
V27.2   MOTHER WITH TWINS BOTH LIVEBORN
V27.3   MOTHER WITH TWINS ONE LIVEBORN AND ONE STILLBORN
V27.4   MOTHER WITH TWINS BOTH STILLBORN
V27.5   MOTHER WITH OTHER MULTIPLE BIRTH ALL LIVEBORN
V27.6   MOTHER WITH OTHER MULTIPLE BIRTH SOME LIVEBORN
V27.7   MOTHER WITH OTHER MULTIPLE BIRTH ALL STILLBORN
V27.9   MOTHER WITH UNSPECIFIED OUTCOME OF DELIVERY
Procedure codes 
72.0   LOW FORCEPS OPERATION
72.1   LOW FORCEPS OPERATION WITH EPISIOTOMY
72.2   MID FORCEPS OPERATION
72.21   MID FORCEPS OPERATION WITH EPISIOTOMY
72.29   OTHER MID FORCEPS OPERATION
72.3   HIGH FORCEPS OPERATION
72.31   HIGH FORCEPS OPERATION WITH EPISIOTOMY
72.39   OTHER HIGH FORCEPS OPERATION
Appendix A

72.4   FORCEPS ROTATION OF FETAL HEAD
72.5   BREECH EXTRACTION
72.51   PARTIAL BREECH EXTRACTION WITH FORCEPS TO AFTERCOMING HEAD
72.52   OTHER PARTIAL BREECH EXTRACTION
72.53   TOTAL BREECH EXTRACTION WITH FORCEPS TO AFTERCOMING HEAD
72.54   OTHER TOTAL BREECH EXTRACTION
72.6   FORCEPS APPLICATION TO AFTERCOMING HEAD
72.7   VACUUM EXTRACTION
72.71   VACUUM EXTRACTION WITH EPISIOTOMY
72.79   OTHER VACUUM EXTRACTION
72.8   OTHER SPECIFIED INSTRUMENTAL DELIVERY
72.9   UNSPECIFIED INSTRUMENTAL DELIVERY
73.0   ARTIFICIAL RUPTURE OF MEMBRANES
73.01   INDUCTION OF LABOR BY ARTIFICIAL RUPTURE OF MEMBRANES
73.09   OTHER ARTIFICIAL RUPTURE OF MEMBRANES
73.1   OTHER SURGICAL INDUCTION OF LABOR
73.2   INTERNAL AND COMBINED VERSION AND EXTRACTION
73.21   INTERNAL AND COMBINED VERSION WITHOUT EXTRACTION
73.22   INTERNAL AND COMBINED VERSION WITH EXTRACTION
73.3   FAILED FORCEPS
73.4   MEDICAL INDUCTION OF LABOR
73.5   MANUALLY ASSISTED DELIVERY
73.51   MANUAL ROTATION OF FETAL HEAD
73.59   OTHER MANUALLY ASSISTED DELIVERY
73.6   EPISIOTOMY
73.8   OPERATIONS ON FETUS TO FACILITATE DELIVERY
73.9   OTHER OPERATIONS ASSISTING DELIVERY
73.91   EXTERNAL VERSION ASSISTING DELIVERY
73.92   REPLACEMENT OF PROLAPSED UMBILICAL CORD
73.93   INCISION OF CERVIX TO ASSIST DELIVERY
73.94   PUBIOTOMY TO ASSIST DELIVERY
73.99   OTHER OPERATIONS ASSISTING DELIVERY
74.0   CLASSICAL CESAREAN SECTION
74.1   LOW CERVICAL CESAREAN SECTION
74.2   EXTRAPERITONEAL CESAREAN SECTION
Appendix A

74.3   REMOVAL OF EXTRATUBAL ECTOPIC PREGNANCY
74.4   CESAREAN SECTION OF OTHER SPECIFIED TYPE
74.9   CESAREAN SECTION OF UNSPECIFIED TYPE
74.91   HYSTEROTOMY TO TERMINATE PREGNANCY
74.99   OTHER CESAREAN SECTION OF UNSPECIFIED TYPE
75.4   MANUAL REMOVAL OF RETAINED PLACENTA
75.5   REPAIR OF CURRENT OBSTETRIC LACERATION OF UTERUS
75.6   REPAIR OF OTHER CURRENT OBSTETRIC LACERATION
75.7   MANUAL EXPLORATION OF UTERINE CAVITY, POSTPARTUM
75.9   OTHER OBSTETRIC OPERATIONS
Appendix A

ESRD, defined as 2 codes (either inpatient or outpatient), separated by at least 30 days 
Codes include:
- ICD9 prox codes: 
39.95, Hemodialysis
54.98, Peritoneal dialysis
- ICD9 dx codes: 
585.5x, Chronic kidney disease, Stage V (for ESRD with no mention of dialysis) 
585.6x, End stage renal disease (for ESRD with dialysis) 
V56.0x, encounter for dialysis NOS
V56.8x, encounter for peritoneal dialysis
V45.1x, renal dialysis status
- CPT4 codes: 
90957, 90960, ESRD related services monthly, for patients 12-19 and 20 years of age and older; with 4 or more face-to-face physician 
visits per month
90958, 90961, ESRD related services monthly, for patients 12-19 and 20 years of age and older; with 2-3 face-to-face physician visits per 
month
90959, 90962, ESRD related services monthly, for patients 12-19 and 20 years of age and older; with 1 face-to-face physician visit per 
month
90920, 90921, ESRD related services per full month; for patients 12-19 and twenty years of age and over
90924, 90925, ESRD related services (less than full month), per day; for patients 12-19 and twenty years of age and over
90935, Hemodialysis procedure with single physician evaluation
90937, Hemodialysis procedure requiring repeated evaluation(s) with or without substantial revision of dialysis prescription
90945, Dialysis procedure other than hemodialysis (eg, peritoneal dialysis, hemofiltration, or other continuous renal replacement 
therapies), with single physician evaluation
90947, Dialysis procedure other than hemodialysis (eg, peritoneal dialysis, hemofiltration, or other continuous renal replacement 
therapies) requiring repeated physician evaluations, with or without substantial revision of dialysis prescription
90965, 90966, ESRD related services for home dialysis per full month, for patients 12-19 and 20 years of age and older
90969, 90970, ESRD related services for dialysis less than a full month of service, per day; for patients 12-19 and 20 years of age and 
older
90989, Dialysis training, patient, including helper where applicable, any mode, completed course
90993, Dialysis training, patient, including helper where applicable, any mode, course not completed, per training session
90999, Unlisted dialysis procedure, inpatient or outpatient
99512, Home visit for hemodialysis
- HCPCS codes:
G0257, Unscheduled or emergency dialysis treatment for ESRD patient in a hospital outpatient dept. that is not certified as an ESRD 
facility 
G0314, G0317, ESRD related services during the course of treatment, for patients 12-19 and 20 yrs of age an over to include monitoring 
for the adequacy of nutrition, etc. w/4 or more physician visit per month
G0315, G0318, ESRD related services during the course of treatment, for patients 12-19 and 20yrs of age and over to include monitoring 
for the adequacy of nutrition, etc. w/2 or 3 physician visit per month
Dialysis codes
Appendix A

o t e adequacy o
ut t o , etc. w/
o 3 p ys c a v s t pe
o t
G0316, G0319, ESRD related services during the course of treatment, for patients 12-19 and 20 yrs of age and over to include monitoring 
for the adequacy of nutrition, etc. w/1 physician visit per month
G0322, G0323, ESRD related services for home dialysis patients per full month: for patients 12-19 and 20 yrs of age and over to include 
monitoring for adequacy of nutrition and etc.
G0326, G0327, ESRD related services for home dialysis (less than full month), per day; for patients 12-19 and 20 yrs of age and over
S9335, Home therapy, hemodialysis; administrative services, professional pharmacy services, care coordination, and all necessary 
supplies and equipment (drugs and nursing services coded separately), per diem
S9339, Home therapy, peritoneal dialysis, administrative services, care coordination and all necessary supplies and equipment, per diem
OR
Kidney transplant, defined as either 1 inpatient or 1 outpatient code
Codes include:
-ICD9 dx codes:
V42.0x, Kidney transplant status
996.81 Complications of transplanted kidney
-ICD9 prox codes: 
55.6x, Transplant of kidney (Exclude 55.61)
- CPT4 codes:
50360, Renal allotransplantation, implantation, graft, w/o donor & recipient nephrectomy
 50365, Renal allotransplantation, implantation, graft, w/ donor & recipient nephrectomy
Appendix A

 
AFTER PS MATCHING
Optum 
MarketScan
Medicare
BEFORE PS MATCHING
The c-statistics for the propensity score model, pre-matching was 0.769. The post-matching c-statistic 
was 0.523.
The c-statistics for the propensity score model, pre-matching was 0.769. The post-matching 
c-statistic was 0.521.
The c-statistics for the propensity score model, pre-matching was 0.773. The post-matching c-statistic 
was 0.519.
Appendix B: Canagliflozin vs DPP4i

Variable
Reference- DPP4i
Exposure- Canagliflozin
Reference- DPP4i
Exposure- Canagliflozin
Reference- DPP4i
Exposure- 
Canagliflozin
Reference- DPP4i
Exposure- Canagliflozin
St. Diff.
Number of patients
                                          92,973                                           21,346 
98,975
                                         
26,910
                                         
258,794
                                    
35,115
                       
                                       450,742                                           83,371 
Age
...mean (sd)
67.55 (9.32)
62.19 (7.89)
62.13 (8.88)
59.26 (6.45)
73.88 (6.99)
70.94 (5.13)
69.99 (7.96)
64.93 (6.36)
0.70
...median [IQR]
68.00 [60.00, 74.00]
61.00 [56.00, 68.00]
61.00 [56.00, 66.00]
59.00 [54.00, 63.00]
72.00 [68.00, 78.00]0.00 [67.00, 74.00]
68.76 (7.96)
64.15 (6.36)
0.64
Age categories 
...18 - 54; n (%)
9,311 (10.0%)
4,143 (19.4%)
19,542 (19.7%)
6,882 (25.6%)
0 (0.0%)
0 (0.0%)
28,853 (6.4%)
11,025 (13.2%)
-0.23
...55 - 64; n (%)
23,950 (25.8%)
9,021 (42.3%)
50,842 (51.4%)
15,706 (58.4%)
3,273 (1.3%)
396 (1.1%)
78,065 (17.3%)
25,123 (30.1%)
-0.30
...65 - 74; n (%)
38,089 (41.0%)
6,682 (31.3%)
17,664 (17.8%)
3,566 (13.3%)
152,505 (58.9%)
27,352 (77.9%)
208,258 (46.2%)
37,600 (45.1%)
0.02
...>= 75; n (%)
21,623 (23.3%)
1,500 (7.0%)
10,927 (11.0%)
756 (2.8%)
103,016 (39.8%)
7,367 (21.0%)
135,566 (30.1%)
9,623 (11.5%)
0.47
Gender 
...Males; n (%)
46,266 (49.8%)
12,127 (56.8%)
54,577 (55.1%)
15,161 (56.3%)
113,623 (43.9%)
18,052 (51.4%)
214,466 (47.6%)
45,340 (54.4%)
-0.14
...Females; n (%)
46,707 (50.2%)
9,219 (43.2%)
44,398 (44.9%)
11,749 (43.7%)
145,171 (56.1%)
17,063 (48.6%)
236,276 (52.4%)
38,031 (45.6%)
0.14
Race 
...White; n (%)
N/A
N/A
N/A
N/A
191,721 (74.1%)
28,985 (82.5%)
191,721 (74.1%)
28,985 (82.5%)
-0.20
...Black; n (%)
N/A
N/A
N/A
N/A
30,531 (11.8%)
2,789 (7.9%)
30,531 (11.8%)
2,789 (7.9%)
0.13
...Asian; n (%)
N/A
N/A
N/A
N/A
12,516 (4.8%)
906 (2.6%)
12,516 (4.8%)
906 (2.6%)
0.12
...Hispanic; n (%)
N/A
N/A
N/A
N/A
12,026 (4.6%)
951 (2.7%)
12,026 (4.6%)
951 (2.7%)
0.10
...North American Native; n (%)
N/A
N/A
N/A
N/A
1,608 (0.6%)
130 (0.4%)
1,608 (0.6%)
130 (0.4%)
0.03
...Other/Unknown; n (%)
N/A
N/A
N/A
N/A
10,392 (4.0%)
1,354 (3.9%)
10,392 (4.0%)
1,354 (3.9%)
0.01
Region   (lumping missing&other category with West)
...Northeast; n (%)
11,368 (12.2%)
1,714 (8.0%)
19,209 (19.4%)
4,647 (17.3%)
49,085 (19.0%)
5,891 (16.8%)
79,662 (17.7%)
12,252 (14.7%)
0.08
...South; n (%)
46,486 (50.0%)
11,429 (53.5%)
21,785 (22.0%)
4,977 (18.5%)
109,273 (42.2%)
15,802 (45.0%)
177,544 (39.4%)
32,208 (38.6%)
0.02
...Midwest; n (%)
16,955 (18.2%)
4,613 (21.6%)
46,018 (46.5%)
14,463 (53.7%)
55,845 (21.6%)
7,955 (22.7%)
118,818 (26.4%)
27,031 (32.4%)
-0.13
...West; n (%)
18,164 (19.5%)
3,590 (16.8%)
10,722 (10.8%)
2,533 (9.4%)
44,591 (17.2%)
5,467 (15.6%)
73,477 (16.3%)
11,590 (13.9%)
0.07
...Unknown+missing; n (%)
N/A
N/A
1,241 (1.3%)
290 (1.1%)
N/A
N/A
1,241 (1.3%)
290 (1.1%)
0.02
CV Covariates
Ischemic heart disease; n (%)
17,210 (18.5%)
3,092 (14.5%)
13,876 (14.0%)
3,306 (12.3%)
67,253 (26.0%)
8,851 (25.2%)
98,339 (21.8%)
15,249 (18.3%)
0.09
Acute MI; n (%)
350 (0.4%)
57 (0.3%)
321 (0.3%)
68 (0.3%)
1,182 (0.5%)
123 (0.4%)
1,853 (0.4%)
248 (0.3%)
0.02
ACS/unstable angina; n (%)
438 (0.5%)
95 (0.4%)
398 (0.4%)
103 (0.4%)
1,445 (0.6%)
184 (0.5%)
2,281 (0.5%)
382 (0.5%)
0.00
Old MI; n (%)
2,139 (2.3%)
367 (1.7%)
995 (1.0%)
200 (0.7%)
7,156 (2.8%)
875 (2.5%)
10,290 (2.3%)
1,442 (1.7%)
0.04
Stable angina; n (%)
2,635 (2.8%)
432 (2.0%)
1,655 (1.7%)
351 (1.3%)
7,598 (2.9%)
989 (2.8%)
11,888 (2.6%)
1,772 (2.1%)
0.03
Coronary atherosclerosis and other forms of chronic 
ischemic heart disease; n (%)
16,133 (17.4%)
2,910 (13.6%)
13,142 (13.3%)
3,136 (11.7%)
64,446 (24.9%)
8,516 (24.3%)
93,721 (20.8%)
14,562 (17.5%)
0.08
Other atherosclerosis with ICD10  ; n (%)
595 (0.6%)
96 (0.4%)
566 (0.6%)
150 (0.6%)
3,406 (1.3%)
400 (1.1%)
4,567 (1.0%)
646 (0.8%)
0.02
Previous cardiac procedure (CABG or PTCA or Stent) ; n (%)
153 (0.2%)
27 (0.1%)
165 (0.2%)
38 (0.1%)
410 (0.2%)
70 (0.2%)
#VALUE!
135 (0.2%)
#VALUE!
History of CABG or PTCA; n (%)
3,786 (4.1%)
645 (3.0%)
1,733 (1.8%)
389 (1.4%)
16,353 (6.3%)
2,097 (6.0%)
21,872 (4.9%)
3,131 (3.8%)
0.05
Any stroke; n (%)
3,557 (3.8%)
526 (2.5%)
2,842 (2.9%)
511 (1.9%)
15,686 (6.1%)
1,822 (5.2%)
22,085 (4.9%)
2,859 (3.4%)
0.08
Ischemic stroke (w and w/o mention of cerebral 
infarction); n (%)
3,535 (3.8%)
524 (2.5%)
2,824 (2.9%)
508 (1.9%)
15,576 (6.0%)
1,817 (5.2%)
21,935 (4.9%)
2,849 (3.4%)
0.08
Hemorrhagic stroke; n (%)
40 (0.0%)
5 (0.0%)
30 (0.0%)
4 (0.0%)
**
**
**
**
**
TIA; n (%)
406 (0.4%)
63 (0.3%)
318 (0.3%)
55 (0.2%)
1,670 (0.6%)
173 (0.5%)
2,394 (0.5%)
291 (0.3%)
0.03
Other cerebrovascular disease; n (%)
974 (1.0%)
135 (0.6%)
632 (0.6%)
97 (0.4%)
4,269 (1.6%)
353 (1.0%)
5,875 (1.3%)
585 (0.7%)
0.06
Late effects of cerebrovascular disease; n (%)
950 (1.0%)
98 (0.5%)
398 (0.4%)
67 (0.2%)
3,602 (1.4%)
261 (0.7%)
4,950 (1.1%)
426 (0.5%)
0.07
Cerebrovascular procedure; n (%)
34 (0.0%)
7 (0.0%)
41 (0.0%)
4 (0.0%)
133 (0.1%)
18 (0.1%)
208 (0.0%)
29 (0.0%)
#DIV/0!
Heart failure (CHF); n (%)
6,529 (7.0%)
824 (3.9%)
3,776 (3.8%)
566 (2.1%)
25,130 (9.7%)
2,306 (6.6%)
35,435 (7.9%)
3,696 (4.4%)
0.15
Peripheral Vascular Disease (PVD) or PVD Surgery ; n (%)
6,053 (6.5%)
924 (4.3%)
3,642 (3.7%)
717 (2.7%)
25,306 (9.8%)
2,686 (7.6%)
35,001 (7.8%)
4,327 (5.2%)
0.11
Atrial fibrillation; n (%)
5,948 (6.4%)
916 (4.3%)
4,563 (4.6%)
792 (2.9%)
27,072 (10.5%)
3,013 (8.6%)
37,583 (8.3%)
4,721 (5.7%)
0.10
Other cardiac dysrhythmia; n (%)
7,501 (8.1%)
1,129 (5.3%)
5,013 (5.1%)
865 (3.2%)
29,407 (11.4%)
3,368 (9.6%)
41,921 (9.3%)
5,362 (6.4%)
0.11
Cardiac conduction disorders; n (%)
2,036 (2.2%)
285 (1.3%)
1,360 (1.4%)
246 (0.9%)
8,527 (3.3%)
956 (2.7%)
11,923 (2.6%)
1,487 (1.8%)
0.05
Other CVD; n (%)
8,272 (8.9%)
1,281 (6.0%)
6,502 (6.6%)
1,292 (4.8%)
33,542 (13.0%)
3,782 (10.8%)
48,316 (10.7%)
6,355 (7.6%)
0.11
Diabetes-related complications
Diabetic retinopathy; n (%)
6,055 (6.5%)
1,287 (6.0%)
3,395 (3.4%)
1,172 (4.4%)
17,502 (6.8%)
2,693 (7.7%)
26,952 (6.0%)
5,152 (6.2%)
-0.01
Diabetes with other ophthalmic manifestations; n (%)
808 (0.9%)
139 (0.7%)
2,103 (2.1%)
739 (2.7%)
6,484 (2.5%)
992 (2.8%)
9,395 (2.1%)
1,870 (2.2%)
-0.01
Retinal detachment, vitreous hemorrhage, vitrectomy; n 
(%)
350 (0.4%)
80 (0.4%)
288 (0.3%)
77 (0.3%)
908 (0.4%)
149 (0.4%)
1,546 (0.3%)
306 (0.4%)
-0.02
Retinal laser coagulation therapy; n (%)
483 (0.5%)
122 (0.6%)
451 (0.5%)
148 (0.5%)
1,384 (0.5%)
225 (0.6%)
2,318 (0.5%)
495 (0.6%)
-0.01
Occurrence of Diabetic Neuropathy  ; n (%)
16,540 (17.8%)
3,792 (17.8%)
9,680 (9.8%)
3,123 (11.6%)
44,854 (17.3%)
7,033 (20.0%)
71,074 (15.8%)
13,948 (16.7%)
-0.02
Unmatched
Optum
MarketScan
Medicare
POOLED
Table 1

Occurrence of diabetic nephropathy  with ICD10 ; n (%)
15,236 (16.4%)
2,186 (10.2%)
6,571 (6.6%)
1,538 (5.7%)
28,980 (11.2%)
2,914 (8.3%)
50,787 (11.3%)
6,638 (8.0%)
0.11
Hypoglycemia ; n (%)
1,930 (2.1%)
459 (2.2%)
1,787 (1.8%)
678 (2.5%)
6,000 (2.3%)
829 (2.4%)
9,717 (2.2%)
1,966 (2.4%)
-0.01
Hyperglycemia; n (%)
3,471 (3.7%)
661 (3.1%)
2,989 (3.0%)
672 (2.5%)
10,518 (4.1%)
1,135 (3.2%)
16,978 (3.8%)
2,468 (3.0%)
0.04
Disorders of fluid electrolyte and acid-base balance; n (%)
5,638 (6.1%)
681 (3.2%)
3,600 (3.6%)
582 (2.2%)
18,043 (7.0%)
1,435 (4.1%)
27,281 (6.1%)
2,698 (3.2%)
0.14
Diabetic ketoacidosis; n (%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
000 (0.0%)
00 (0.0%)
#DIV/0!
Hyperosmolar hyperglycemic nonketotic syndrome 
(HONK); n (%)
460 (0.5%)
97 (0.5%)
402 (0.4%)
92 (0.3%)
1,230 (0.5%)
172 (0.5%)
2,092 (0.5%)
361 (0.4%)
0.01
Diabetes with peripheral circulatory disorders with ICD-
10  ; n (%)
6,454 (6.9%)
1,015 (4.8%)
2,805 (2.8%)
698 (2.6%)
17,985 (6.9%)
2,091 (6.0%)
27,244 (6.0%)
3,804 (4.6%)
0.06
Diabetic Foot; n (%)
1,580 (1.7%)
286 (1.3%)
1,274 (1.3%)
345 (1.3%)
5,641 (2.2%)
715 (2.0%)
8,495 (1.9%)
1,346 (1.6%)
0.02
Gangrene ; n (%)
133 (0.1%)
20 (0.1%)
74 (0.1%)
10 (0.0%)
347 (0.1%)
28 (0.1%)
554 (0.1%)
58 (0.1%)
0.00
Lower extremity amputation; n (%)
492 (0.5%)
63 (0.3%)
134 (0.1%)
32 (0.1%)
1,170 (0.5%)
109 (0.3%)
1,796 (0.4%)
204 (0.2%)
0.04
Osteomyelitis; n (%)
356 (0.4%)
53 (0.2%)
266 (0.3%)
67 (0.2%)
910 (0.4%)
98 (0.3%)
1,532 (0.3%)
218 (0.3%)
0.00
Skin infections ; n (%)
4,261 (4.6%)
989 (4.6%)
4,253 (4.3%)
1,163 (4.3%)
14,883 (5.8%)
1,984 (5.7%)
23,397 (5.2%)
4,136 (5.0%)
0.01
Erectile dysfunction; n (%)
2,518 (2.7%)
767 (3.6%)
2,415 (2.4%)
759 (2.8%)
5,288 (2.0%)
1,093 (3.1%)
10,221 (2.3%)
2,619 (3.1%)
-0.05
Diabetes with unspecified complication; n (%)
4,841 (5.2%)
1,089 (5.1%)
4,301 (4.3%)
1,170 (4.3%)
12,495 (4.8%)
1,873 (5.3%)
21,637 (4.8%)
4,132 (5.0%)
-0.01
Diabetes mellitus without mention of complications; n 
(%)
79,354 (85.4%)
18,017 (84.4%)
90,348 (91.3%)
24,734 (91.9%)
239,419 (92.5%)
32,095 (91.4%)
409,121 (90.8%)
74,846 (89.8%)
0.03
Hypertension: 1 inpatient or 2 outpatient claims within 
365 days; n (%)
86,092 (92.6%)
19,597 (91.8%)
85,616 (86.5%)
23,560 (87.6%)
247,659 (95.7%)
33,591 (95.7%)
419,367 (93.0%)
76,748 (92.1%)
0.03
Hyperlipidemia ; n (%)
69,860 (75.1%)
16,586 (77.7%)
70,415 (71.1%)
20,473 (76.1%)
205,187 (79.3%)
28,928 (82.4%)
345,462 (76.6%)
65,987 (79.1%)
-0.06
Edema; n (%)
5,759 (6.2%)
984 (4.6%)
3,668 (3.7%)
862 (3.2%)
22,340 (8.6%)
2,520 (7.2%)
31,767 (7.0%)
4,366 (5.2%)
0.08
Renal Dysfunction (non-diabetic) ; n (%)
20,147 (21.7%)
2,104 (9.9%)
10,409 (10.5%)
1,423 (5.3%)
56,908 (22.0%)
4,185 (11.9%)
87,464 (19.4%)
7,712 (9.3%)
0.29
Occurrence of acute renal disease ; n (%)
2,464 (2.7%)
173 (0.8%)
1,510 (1.5%)
132 (0.5%)
7,853 (3.0%)
371 (1.1%)
11,827 (2.6%)
676 (0.8%)
0.14
Occurrence of chronic renal insufficiency; n (%)
17,268 (18.6%)
1,743 (8.2%)
7,789 (7.9%)
1,056 (3.9%)
48,344 (18.7%)
3,461 (9.9%)
73,401 (16.3%)
6,260 (7.5%)
0.27
Chronic kidney disease ; n (%)
16,746 (18.0%)
1,620 (7.6%)
7,378 (7.5%)
898 (3.3%)
46,107 (17.8%)
3,184 (9.1%)
70,231 (15.6%)
5,702 (6.8%)
0.28
CKD Stage 3-4; n (%)
11,687 (12.6%)
834 (3.9%)
4,947 (5.0%)
451 (1.7%)
32,580 (12.6%)
1,859 (5.3%)
49,214 (10.9%)
3,144 (3.8%)
0.27
Occurrence of hypertensive nephropathy; n (%)
7,429 (8.0%)
682 (3.2%)
3,128 (3.2%)
368 (1.4%)
19,295 (7.5%)
1,185 (3.4%)
29,852 (6.6%)
2,235 (2.7%)
0.19
Occurrence of miscellaneous renal insufficiency ; n (%)
4,104 (4.4%)
422 (2.0%)
2,795 (2.8%)
398 (1.5%)
15,575 (6.0%)
1,163 (3.3%)
22,474 (5.0%)
1,983 (2.4%)
0.14
Glaucoma or cataracts ; n (%)
18,671 (20.1%)
3,608 (16.9%)
14,922 (15.1%)
3,666 (13.6%)
68,628 (26.5%)
9,616 (27.4%)
102,221 (22.7%)
16,890 (20.3%)
0.06
Cellulitis or abscess of toe; n (%)
1,051 (1.1%)
190 (0.9%)
740 (0.7%)
166 (0.6%)
3,049 (1.2%)
385 (1.1%)
4,840 (1.1%)
741 (0.9%)
0.02
Foot ulcer; n (%)
1,516 (1.6%)
268 (1.3%)
1,254 (1.3%)
347 (1.3%)
5,567 (2.2%)
708 (2.0%)
8,337 (1.8%)
1,323 (1.6%)
0.02
Bladder stones; n (%)
99 (0.1%)
12 (0.1%)
86 (0.1%)
12 (0.0%)
343 (0.1%)
50 (0.1%)
528 (0.1%)
74 (0.1%)
0.00
Kidney stones; n (%)
1,802 (1.9%)
330 (1.5%)
1,911 (1.9%)
471 (1.8%)
5,922 (2.3%)
763 (2.2%)
9,635 (2.1%)
1,564 (1.9%)
0.01
Urinary tract infections (UTIs); n (%)
7,598 (8.2%)
1,041 (4.9%)
5,074 (5.1%)
1,047 (3.9%)
30,499 (11.8%)
2,805 (8.0%)
43,171 (9.6%)
4,893 (5.9%)
0.14
Dipstick urinalysis; n (%)
33,076 (35.6%)
6,473 (30.3%)
30,675 (31.0%)
8,063 (30.0%)
99,731 (38.5%)
12,329 (35.1%)
163,482 (36.3%)
26,865 (32.2%)
0.09
Non-dipstick urinalysis; n (%)
41,645 (44.8%)
9,752 (45.7%)
36,404 (36.8%)
11,482 (42.7%)
111,191 (43.0%)
16,168 (46.0%)
189,240 (42.0%)
37,402 (44.9%)
-0.06
Urine function test; n (%)
1,859 (2.0%)
275 (1.3%)
1,802 (1.8%)
345 (1.3%)
7,703 (3.0%)
906 (2.6%)
11,364 (2.5%)
1,526 (1.8%)
0.05
Cytology; n (%)
537 (0.6%)
88 (0.4%)
639 (0.6%)
126 (0.5%)
2,033 (0.8%)
220 (0.6%)
3,209 (0.7%)
434 (0.5%)
0.03
Cystos; n (%)
820 (0.9%)
135 (0.6%)
855 (0.9%)
185 (0.7%)
2,921 (1.1%)
335 (1.0%)
4,596 (1.0%)
655 (0.8%)
0.02
Other Covariates
Liver disease; n (%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
#VALUE!
000 (0.0%)
#VALUE!
Osteoarthritis; n (%)
11,742 (12.6%)
2,168 (10.2%)
7,946 (8.0%)
1,907 (7.1%)
45,826 (17.7%)
5,609 (16.0%)
65,514 (14.5%)
9,684 (11.6%)
0.09
Other arthritis, arthropathies and musculoskeletal pain; n 
(%)
27,439 (29.5%)
5,725 (26.8%)
24,107 (24.4%)
6,419 (23.9%)
94,733 (36.6%)
11,953 (34.0%)
146,279 (32.5%)
24,097 (28.9%)
0.08
Dorsopathies; n (%)
16,535 (17.8%)
3,757 (17.6%)
14,621 (14.8%)
4,093 (15.2%)
55,400 (21.4%)
7,711 (22.0%)
86,556 (19.2%)
15,561 (18.7%)
0.01
Fractures; n (%)
2,037 (2.2%)
322 (1.5%)
1,777 (1.8%)
385 (1.4%)
7,550 (2.9%)
772 (2.2%)
11,364 (2.5%)
1,479 (1.8%)
0.05
Falls ; n (%)
2,630 (2.8%)
343 (1.6%)
955 (1.0%)
136 (0.5%)
9,355 (3.6%)
716 (2.0%)
12,940 (2.9%)
1,195 (1.4%)
0.10
Osteoporosis; n (%)
4,528 (4.9%)
507 (2.4%)
1,890 (1.9%)
297 (1.1%)
19,484 (7.5%)
1,793 (5.1%)
25,902 (5.7%)
2,597 (3.1%)
0.13
Hyperthyroidism; n (%)
607 (0.7%)
115 (0.5%)
493 (0.5%)
105 (0.4%)
2,277 (0.9%)
255 (0.7%)
3,377 (0.7%)
475 (0.6%)
0.01
Hypothyroidism ; n (%)
14,093 (15.2%)
3,015 (14.1%)
11,014 (11.1%)
3,225 (12.0%)
31,705 (12.3%)
4,238 (12.1%)
56,812 (12.6%)
10,478 (12.6%)
0.00
Other disorders of thyroid gland ; n (%)
3,204 (3.4%)
782 (3.7%)
2,893 (2.9%)
984 (3.7%)
9,716 (3.8%)
1,454 (4.1%)
15,813 (3.5%)
3,220 (3.9%)
-0.02
Depression; n (%)
6,370 (6.9%)
1,494 (7.0%)
5,344 (5.4%)
1,597 (5.9%)
22,933 (8.9%)
2,897 (8.3%)
34,647 (7.7%)
5,988 (7.2%)
0.02
Anxiety; n (%)
6,068 (6.5%)
1,357 (6.4%)
4,637 (4.7%)
1,230 (4.6%)
18,829 (7.3%)
2,345 (6.7%)
29,534 (6.6%)
4,932 (5.9%)
0.03
Sleep_Disorder; n (%)
4,861 (5.2%)
1,601 (7.5%)
7,480 (7.6%)
3,032 (11.3%)
16,931 (6.5%)
2,968 (8.5%)
29,272 (6.5%)
7,601 (9.1%)
-0.10
Dementia; n (%)
3,192 (3.4%)
200 (0.9%)
1,443 (1.5%)
119 (0.4%)
16,772 (6.5%)
910 (2.6%)
21,407 (4.7%)
1,229 (1.5%)
0.19
Delirium; n (%)
725 (0.8%)
57 (0.3%)
410 (0.4%)
31 (0.1%)
3,458 (1.3%)
182 (0.5%)
4,593 (1.0%)
270 (0.3%)
0.09
Psychosis; n (%)
831 (0.9%)
88 (0.4%)
440 (0.4%)
52 (0.2%)
4,373 (1.7%)
258 (0.7%)
5,644 (1.3%)
398 (0.5%)
0.08
Obesity; n (%)
18,832 (20.3%)
5,799 (27.2%)
14,581 (14.7%)
5,276 (19.6%)
34,677 (13.4%)
6,927 (19.7%)
68,090 (15.1%)
18,002 (21.6%)
-0.17
Overweight; n (%)
5,629 (6.1%)
1,083 (5.1%)
2,441 (2.5%)
593 (2.2%)
9,232 (3.6%)
1,237 (3.5%)
17,302 (3.8%)
2,913 (3.5%)
0.02
Smoking; n (%)
8,487 (9.1%)
1,743 (8.2%)
5,746 (5.8%)
1,323 (4.9%)
28,073 (10.8%)
3,758 (10.7%)
42,306 (9.4%)
6,824 (8.2%)
0.04
Alcohol abuse or dependence; n (%)
16 (0.0%)
2 (0.0%)
22 (0.0%)
5 (0.0%)
**
**
**
**
**
Drug abuse or dependence; n (%)
41 (0.0%)
7 (0.0%)
13 (0.0%)
3 (0.0%)
**
**
**
**
**
COPD; n (%)
6,608 (7.1%)
1,038 (4.9%)
3,790 (3.8%)
766 (2.8%)
23,441 (9.1%)
2,714 (7.7%)
33,839 (7.5%)
4,518 (5.4%)
0.09
Table 1

Asthma; n (%)
4,366 (4.7%)
934 (4.4%)
3,552 (3.6%)
957 (3.6%)
13,189 (5.1%)
1,815 (5.2%)
21,107 (4.7%)
3,706 (4.4%)
0.01
Obstructive sleep apnea; n (%)
7,604 (8.2%)
2,530 (11.9%)
8,904 (9.0%)
3,255 (12.1%)
15,485 (6.0%)
3,345 (9.5%)
31,993 (7.1%)
9,130 (11.0%)
-0.14
Pneumonia; n (%)
1,613 (1.7%)
234 (1.1%)
1,356 (1.4%)
241 (0.9%)
6,178 (2.4%)
541 (1.5%)
9,147 (2.0%)
1,016 (1.2%)
0.06
Imaging; n (%)
34 (0.0%)
6 (0.0%)
21 (0.0%)
2 (0.0%)
**
**
**
**
**
Diabetes Medications
DM Medications - AGIs; n (%)
513 (0.6%)
116 (0.5%)
358 (0.4%)
99 (0.4%)
1,637 (0.6%)
273 (0.8%)
2,508 (0.6%)
488 (0.6%)
0.00
DM Medications - Glitazones; n (%)
7,470 (8.0%)
2,132 (10.0%)
7,539 (7.6%)
2,659 (9.9%)
20,110 (7.8%)
3,517 (10.0%)
35,119 (7.8%)
8,308 (10.0%)
-0.08
DM Medications - Insulin; n (%)
15,209 (16.4%)
5,869 (27.5%)
13,275 (13.4%)
8,133 (30.2%)
44,262 (17.1%)
11,188 (31.9%)
72,746 (16.1%)
25,190 (30.2%)
-0.34
DM Medications - Meglitinides; n (%)
1,069 (1.1%)
220 (1.0%)
1,218 (1.2%)
346 (1.3%)
4,683 (1.8%)
576 (1.6%)
6,970 (1.5%)
1,142 (1.4%)
0.01
DM Medications - Metformin; n (%)
68,898 (74.1%)
16,690 (78.2%)
78,748 (79.6%)
21,017 (78.1%)
181,431 (70.1%)
26,156 (74.5%)
329,077 (73.0%)
63,863 (76.6%)
-0.08
Concomitant initiation or current use of 2nd Generation 
SUs; n (%)
33,158 (35.7%)
6,949 (32.6%)
31,388 (31.7%)
8,362 (31.1%)
97,534 (37.7%)
13,082 (37.3%)
162,080 (36.0%)
28,393 (34.1%)
0.04
Concomitant initiation or current use of AGIs; n (%)
378 (0.4%)
82 (0.4%)
250 (0.3%)
54 (0.2%)
1,197 (0.5%)
180 (0.5%)
1,825 (0.4%)
316 (0.4%)
0.00
Concomitant initiation or current use of Glitazones; n (%)
5,771 (6.2%)
1,613 (7.6%)
5,925 (6.0%)
2,013 (7.5%)
15,535 (6.0%)
2,693 (7.7%)
27,231 (6.0%)
6,319 (7.6%)
-0.06
Concomitant initiation or current use of GLP-1 RA; n (%)
1,826 (2.0%)
2,913 (13.6%)
2,187 (2.2%)
4,565 (17.0%)
3,172 (1.2%)
4,049 (11.5%)
7,185 (1.6%)
11,527 (13.8%)
-0.47
Concomitant initiation or current use of Insulin; n (%)
11,555 (12.4%)
4,411 (20.7%)
10,019 (10.1%)
6,296 (23.4%)
34,079 (13.2%)
8,819 (25.1%)
55,653 (12.3%)
19,526 (23.4%)
-0.29
Concomitant initiation or current use of Meglitinides; n 
(%)
786 (0.8%)
142 (0.7%)
875 (0.9%)
222 (0.8%)
3,410 (1.3%)
402 (1.1%)
5,071 (1.1%)
766 (0.9%)
0.02
Concomitant initiation or current use of Metformin; n (%)
59,526 (64.0%)
14,098 (66.0%)
69,344 (70.1%)
17,788 (66.1%)
156,339 (60.4%)
22,344 (63.6%)
285,209 (63.3%)
54,230 (65.0%)
-0.04
Past use of 2nd Generation SUs ; n (%)
6,990 (7.5%)
1,805 (8.5%)
7,050 (7.1%)
2,003 (7.4%)
19,774 (7.6%)
2,765 (7.9%)
33,814 (7.5%)
6,573 (7.9%)
-0.02
Past use of AGIs ; n (%)
135 (0.1%)
34 (0.2%)
108 (0.1%)
45 (0.2%)
440 (0.2%)
93 (0.3%)
683 (0.2%)
172 (0.2%)
0.00
Past use of Glitazones ; n (%)
1,699 (1.8%)
519 (2.4%)
1,614 (1.6%)
646 (2.4%)
4,575 (1.8%)
824 (2.3%)
7,888 (1.8%)
1,989 (2.4%)
-0.04
Past use of GLP-1 RA ; n (%)
1,513 (1.6%)
1,248 (5.8%)
1,750 (1.8%)
1,865 (6.9%)
2,968 (1.1%)
1,792 (5.1%)
6,231 (1.4%)
4,905 (5.9%)
-0.24
Past use of Insulin ; n (%)
3,654 (3.9%)
1,458 (6.8%)
3,257 (3.3%)
1,837 (6.8%)
10,185 (3.9%)
2,370 (6.7%)
17,096 (3.8%)
5,665 (6.8%)
-0.13
Past use of Meglitinides ; n (%)
283 (0.3%)
78 (0.4%)
343 (0.3%)
124 (0.5%)
1,273 (0.5%)
174 (0.5%)
1,899 (0.4%)
376 (0.5%)
-0.01
Past use of metformin (final) ; n (%)
9,372 (10.1%)
2,592 (12.1%)
9,405 (9.5%)
3,229 (12.0%)
25,092 (9.7%)
3,812 (10.9%)
43,869 (9.7%)
9,633 (11.6%)
-0.06
Other Medications
Use of ACE inhibitors; n (%)
48,661 (52.3%)
11,586 (54.3%)
52,091 (52.6%)
14,264 (53.0%)
126,600 (48.9%)
17,572 (50.0%)
227,352 (50.4%)
43,422 (52.1%)
-0.03
Use of ARBs; n (%)
33,271 (35.8%)
7,711 (36.1%)
35,863 (36.2%)
10,233 (38.0%)
92,288 (35.7%)
13,134 (37.4%)
161,422 (35.8%)
31,078 (37.3%)
-0.03
Use of Loop Diuretics ; n (%)
11,784 (12.7%)
1,942 (9.1%)
9,018 (9.1%)
2,198 (8.2%)
47,353 (18.3%)
5,440 (15.5%)
68,155 (15.1%)
9,580 (11.5%)
0.11
Use of other diuretics; n (%)
2,738 (2.9%)
549 (2.6%)
2,657 (2.7%)
689 (2.6%)
9,268 (3.6%)
1,194 (3.4%)
14,663 (3.3%)
2,432 (2.9%)
0.02
Use of nitrates-United; n (%)
4,319 (4.6%)
759 (3.6%)
3,623 (3.7%)
874 (3.2%)
18,544 (7.2%)
2,233 (6.4%)
26,486 (5.9%)
3,866 (4.6%)
0.06
Use of other hypertension drugs; n (%)
7,149 (7.7%)
1,137 (5.3%)
5,872 (5.9%)
1,298 (4.8%)
22,836 (8.8%)
2,590 (7.4%)
35,857 (8.0%)
5,025 (6.0%)
0.08
Use of digoxin; n (%)
1,454 (1.6%)
242 (1.1%)
1,364 (1.4%)
236 (0.9%)
7,836 (3.0%)
768 (2.2%)
10,654 (2.4%)
1,246 (1.5%)
0.07
Use of Anti-arrhythmics; n (%)
1,053 (1.1%)
173 (0.8%)
1,025 (1.0%)
190 (0.7%)
4,813 (1.9%)
503 (1.4%)
6,891 (1.5%)
866 (1.0%)
0.05
Use of COPD/asthma meds; n (%)
13,032 (14.0%)
2,801 (13.1%)
13,214 (13.4%)
3,735 (13.9%)
41,359 (16.0%)
5,761 (16.4%)
67,605 (15.0%)
12,297 (14.7%)
0.01
Use of statins; n (%)
67,725 (72.8%)
15,590 (73.0%)
67,262 (68.0%)
18,843 (70.0%)
190,375 (73.6%)
26,610 (75.8%)
325,362 (72.2%)
61,043 (73.2%)
-0.02
Use of other lipid-lowering drugs; n (%)
10,744 (11.6%)
2,824 (13.2%)
13,362 (13.5%)
4,298 (16.0%)
33,537 (13.0%)
5,264 (15.0%)
57,643 (12.8%)
12,386 (14.9%)
-0.06
Use of antiplatelet agents; n (%)
10,807 (11.6%)
2,095 (9.8%)
11,015 (11.1%)
2,709 (10.1%)
37,758 (14.6%)
4,884 (13.9%)
59,580 (13.2%)
9,688 (11.6%)
0.05
Use of oral anticoagulants (Dabigatran, Rivaroxaban, 
Apixaban, Warfarin); n (%)
5,410 (5.8%)
923 (4.3%)
4,601 (4.6%)
893 (3.3%)
23,012 (8.9%)
2,738 (7.8%)
33,023 (7.3%)
4,554 (5.5%)
0.07
Use of heparin and other low-molecular weight heparins; 
n (%)
194 (0.2%)
21 (0.1%)
8 (0.0%)
0 (0.0%)
578 (0.2%)
66 (0.2%)
780 (0.2%)
087 (0.1%)
0.03
Use of NSAIDs; n (%)
13,827 (14.9%)
3,495 (16.4%)
15,098 (15.3%)
4,443 (16.5%)
39,001 (15.1%)
5,385 (15.3%)
67,926 (15.1%)
13,323 (16.0%)
-0.02
Use of oral corticosteroids; n (%)
11,453 (12.3%)
2,456 (11.5%)
11,415 (11.5%)
2,993 (11.1%)
36,129 (14.0%)
4,819 (13.7%)
58,997 (13.1%)
10,268 (12.3%)
0.02
Use of bisphosphonate (United); n (%)
2,381 (2.6%)
240 (1.1%)
1,015 (1.0%)
162 (0.6%)
9,128 (3.5%)
777 (2.2%)
12,524 (2.8%)
1,179 (1.4%)
0.10
Use of opioids; n (%)
17,277 (18.6%)
4,109 (19.2%)
18,342 (18.5%)
5,363 (19.9%)
51,367 (19.8%)
7,046 (20.1%)
86,986 (19.3%)
16,518 (19.8%)
-0.01
Use of antidepressants; n (%)
19,561 (21.0%)
4,900 (23.0%)
18,887 (19.1%)
6,026 (22.4%)
59,621 (23.0%)
8,616 (24.5%)
98,069 (21.8%)
19,542 (23.4%)
-0.04
Use of antipsychotics; n (%)
1,969 (2.1%)
365 (1.7%)
1,327 (1.3%)
303 (1.1%)
7,692 (3.0%)
698 (2.0%)
10,988 (2.4%)
1,366 (1.6%)
0.06
Use of anticonvulsants; n (%)
13,269 (14.3%)
2,952 (13.8%)
9,838 (9.9%)
3,006 (11.2%)
38,618 (14.9%)
5,337 (15.2%)
61,725 (13.7%)
11,295 (13.5%)
0.01
Use of lithium; n (%)
105 (0.1%)
21 (0.1%)
107 (0.1%)
20 (0.1%)
245 (0.1%)
29 (0.1%)
457 (0.1%)
070 (0.1%)
0.00
Use of Benzos; n (%)
8,001 (8.6%)
1,860 (8.7%)
7,927 (8.0%)
2,274 (8.5%)
26,120 (10.1%)
3,388 (9.6%)
42,048 (9.3%)
7,522 (9.0%)
0.01
Use of anxiolytics/hypnotics; n (%)
4,283 (4.6%)
1,109 (5.2%)
5,008 (5.1%)
1,439 (5.3%)
13,252 (5.1%)
1,813 (5.2%)
22,543 (5.0%)
4,361 (5.2%)
-0.01
Use of dementia meds; n (%)
2,138 (2.3%)
130 (0.6%)
1,145 (1.2%)
84 (0.3%)
12,186 (4.7%)
724 (2.1%)
15,469 (3.4%)
938 (1.1%)
0.16
Use of antiparkinsonian meds; n (%)
1,865 (2.0%)
401 (1.9%)
1,487 (1.5%)
438 (1.6%)
7,223 (2.8%)
996 (2.8%)
10,575 (2.3%)
1,835 (2.2%)
0.01
Any use of pramlintide; n (%)
6 (0.0%)
27 (0.1%)
14 (0.0%)
51 (0.2%)
26 (0.0%)
36 (0.1%)
046 (0.0%)
114 (0.1%)
-0.04
Any use of 1st generation sulfonylureas; n (%)
6 (0.0%)
0 (0.0%)
11 (0.0%)
0 (0.0%)
**
**
**
**
**
Entresto (sacubitril/valsartan); n (%)
133 (0.1%)
14 (0.1%)
40 (0.0%)
4 (0.0%)
153 (0.1%)
13 (0.0%)
326 (0.1%)
031 (0.0%)
0.00
Initiation as monotherapy  ; n (%)
8,025 (8.6%)
1,196 (5.6%)
8,499 (8.6%)
1,307 (4.9%)
19,281 (7.5%)
1,217 (3.5%)
35,805 (7.9%)
3,720 (4.5%)
0.14
Labs
                                       191,948                                           48,256 
Lab values- HbA1c (%) ; n (%)
39,394 (42.4%)
9,243 (43.3%)
6,873 (6.9%)
1,671 (6.2%)
N/A
N/A
46,267 (24.1%)
10,914 (22.6%)
0.04
Lab values- HbA1c (%) (within 3 months) ; n (%)
31,798 (34.2%)
7,578 (35.5%)
5,566 (5.6%)
1,424 (5.3%)
N/A
N/A
37,364 (19.5%)
9,002 (18.7%)
0.02
Lab values- HbA1c (%) (within 6 months) ; n (%)
39,394 (42.4%)
9,243 (43.3%)
6,873 (6.9%)
1,671 (6.2%)
N/A
N/A
46,267 (24.1%)
10,914 (22.6%)
0.04
Table 1

Lab values- BNP; n (%)
754 (0.8%)
133 (0.6%)
105 (0.1%)
4 (0.0%)
N/A
N/A
859 (0.4%)
137 (0.3%)
0.02
Lab values- BNP (within 3 months); n (%)
469 (0.5%)
82 (0.4%)
73 (0.1%)
3 (0.0%)
N/A
N/A
542 (0.3%)
085 (0.2%)
0.02
Lab values- BNP (within 6 months); n (%)
754 (0.8%)
133 (0.6%)
105 (0.1%)
4 (0.0%)
N/A
N/A
859 (0.4%)
137 (0.3%)
0.02
Lab values- BUN (mg/dl); n (%)
39,324 (42.3%)
9,039 (42.3%)
6,660 (6.7%)
1,583 (5.9%)
N/A
N/A
45,984 (24.0%)
10,622 (22.0%)
0.05
Lab values- BUN (mg/dl) (within 3 months); n (%)
31,041 (33.4%)
7,235 (33.9%)
5,215 (5.3%)
1,301 (4.8%)
N/A
N/A
36,256 (18.9%)
8,536 (17.7%)
0.03
Lab values- BUN (mg/dl) (within 6 months); n (%)
39,324 (42.3%)
9,039 (42.3%)
6,660 (6.7%)
1,583 (5.9%)
N/A
N/A
45,984 (24.0%)
10,622 (22.0%)
0.05
Lab values- Creatinine (mg/dl) ; n (%)
40,379 (43.4%)
9,338 (43.7%)
7,075 (7.1%)
1,722 (6.4%)
N/A
N/A
47,454 (24.7%)
11,060 (22.9%)
0.04
Lab values- Creatinine (mg/dl) (within 3 months) ; n (%)
31,911 (34.3%)
7,473 (35.0%)
5,555 (5.6%)
1,428 (5.3%)
N/A
N/A
37,466 (19.5%)
8,901 (18.4%)
0.03
Lab values- Creatinine (mg/dl) (within 6 months) ; n (%)
40,379 (43.4%)
9,338 (43.7%)
7,075 (7.1%)
1,722 (6.4%)
N/A
N/A
47,454 (24.7%)
11,060 (22.9%)
0.04
Lab values- HDL level (mg/dl); n (%)
33,867 (36.4%)
8,008 (37.5%)
6,271 (6.3%)
1,528 (5.7%)
N/A
N/A
40,138 (20.9%)
9,536 (19.8%)
0.03
Lab values- HDL level (mg/dl) (within 3 months); n (%)
25,297 (27.2%)
6,107 (28.6%)
4,752 (4.8%)
1,206 (4.5%)
N/A
N/A
30,049 (15.7%)
7,313 (15.2%)
0.01
Lab values- HDL level (mg/dl) (within 6 months); n (%)
33,867 (36.4%)
8,008 (37.5%)
6,271 (6.3%)
1,528 (5.7%)
N/A
N/A
40,138 (20.9%)
9,536 (19.8%)
0.03
Lab values- LDL level (mg/dl) ; n (%)
34,910 (37.5%)
8,251 (38.7%)
6,464 (6.5%)
1,555 (5.8%)
N/A
N/A
41,374 (21.6%)
9,806 (20.3%)
0.03
Lab values- LDL level (mg/dl) (within 3 months) ; n (%)
26,067 (28.0%)
6,315 (29.6%)
4,889 (4.9%)
1,231 (4.6%)
N/A
N/A
30,956 (16.1%)
7,546 (15.6%)
0.01
Lab values- LDL level (mg/dl) (within 6 months) ; n (%)
34,910 (37.5%)
8,251 (38.7%)
6,464 (6.5%)
1,555 (5.8%)
N/A
N/A
41,374 (21.6%)
9,806 (20.3%)
0.03
Lab values- NT-proBNP; n (%)
109 (0.1%)
12 (0.1%)
17 (0.0%)
0 (0.0%)
N/A
N/A
126 (0.1%)
12 (0.0%)
0.04
Lab values- NT-proBNP (within 3 months); n (%)
65 (0.1%)
7 (0.0%)
12 (0.0%)
0 (0.0%)
N/A
N/A
77 (0.0%)
7 (0.0%)
-
Lab values- NT-proBNP (within 6 months); n (%)
109 (0.1%)
12 (0.1%)
17 (0.0%)
0 (0.0%)
N/A
N/A
126 (0.1%)
12 (0.0%)
-
Lab values- Total cholesterol (mg/dl) ; n (%)
34,343 (36.9%)
8,172 (38.3%)
6,281 (6.3%)
1,541 (5.7%)
N/A
N/A
40,624 (21.2%)
9,713 (20.1%)
0.03
Lab values- Total cholesterol (mg/dl) (within 3 months) ; n 
(%)
25,693 (27.6%)
6,257 (29.3%)
4,760 (4.8%)
1,222 (4.5%)
N/A
N/A
30,453 (15.9%)
7,479 (15.5%)
0.01
Lab values- Total cholesterol (mg/dl) (within 6 months) ; n 
(%)
34,343 (36.9%)
8,172 (38.3%)
6,281 (6.3%)
1,541 (5.7%)
N/A
N/A
40,624 (21.2%)
9,713 (20.1%)
0.03
Lab values- Triglyceride level (mg/dl); n (%)
34,067 (36.6%)
8,123 (38.1%)
6,220 (6.3%)
1,515 (5.6%)
N/A
N/A
40,287 (21.0%)
9,638 (20.0%)
0.02
Lab values- Triglyceride level (mg/dl) (within 3 months); n 
(%)
25,487 (27.4%)
6,217 (29.1%)
4,718 (4.8%)
1,205 (4.5%)
N/A
N/A
30,205 (15.7%)
7,422 (15.4%)
0.01
Lab values- Triglyceride level (mg/dl) (within 6 months); n 
(%)
34,067 (36.6%)
8,123 (38.1%)
6,220 (6.3%)
1,515 (5.6%)
N/A
N/A
40,287 (21.0%)
9,638 (20.0%)
0.02
Lab result number- HbA1c (%) mean (only 2 to 20 
included) 
39,196
                                         
9,185
                                            
6,611
                                            
1,615
                                            
N/A
N/A                                           45,807                                           10,800 
...mean (sd)
8.25 (1.74)
8.63 (1.75)
8.43 (1.84)
8.63 (1.70)
N/A
N/A
8.28 (1.75)
8.63 (1.74)
-0.20
...median [IQR]
7.90 [7.10, 9.10]
8.30 [7.40, 9.60]
8.00 [7.10, 9.30]
8.30 [7.40, 9.60]
N/A
N/A
7.91 (1.75)
8.30 (1.74)
-0.22
...Missing; n (%)
53,777 (57.8%)
12,161 (57.0%)
92,364 (93.3%)
25,295 (94.0%)
N/A
N/A
146,141 (76.1%)
37,456 (77.6%)
-0.04
Lab result number- BNP mean 
754
                                                
133
                                                
105
                                                
4
                                                      
N/A
N/A                                                  859                                                  137 
...mean (sd)
155.94 (289.65)
91.38 (156.35)
3,194.66 (27,330.33)
335.38 (447.47)
N/A
N/A
527.38 (9530.18)
98.50 (169.01)
0.06
...median [IQR]
66.30 [28.18, 168.20]
42.60 [19.25, 88.20]
103.50 [36.75, 363.17]
192.50 [4.25, 809.38]
N/A
N/A
#VALUE!
46.98 (169.01)
#VALUE!
...Missing; n (%)
92,219 (99.2%)
21,213 (99.4%)
98,870 (99.9%)
26,906 (100.0%)
N/A
N/A
191,089 (99.6%)
48,119 (99.7%)
-0.02
Lab result number- BUN (mg/dl) mean 
                                          39,324                                              9,039                                              6,660                                              1,583 
N/A
N/A                                           45,984                                           10,622 
...mean (sd)
18.81 (7.90)
16.88 (5.75)
870.71 (12,029.05)
2,719.95 (20,223.13)
N/A
N/A
142.19 (4577.70)
419.72 (7805.66)
-0.04
...median [IQR]
17.00 [14.00, 22.00]
16.00 [13.00, 19.50]
16.00 [13.00, 20.00]
16.00 [13.00, 20.00]
N/A
N/A
#VALUE!
#VALUE!
#VALUE!
...Missing; n (%)
53,649 (57.7%)
12,307 (57.7%)
92,315 (93.3%)
25,327 (94.1%)
N/A
N/A
145,964 (76.0%)
37,634 (78.0%)
-0.05
Lab result number- Creatinine (mg/dl) mean (only 0.1 to 
15 included) 
                                          40,096                                              9,267                                              6,197                                              1,566 
N/A
N/A                                           46,293                                           10,833 
...mean (sd)
1.04 (0.39)
0.92 (0.24)
1.00 (0.38)
0.93 (0.23)
N/A
N/A
1.03 (0.39)
0.92 (0.24)
0.34
...median [IQR]
0.96 [0.79, 1.19]
0.89 [0.75, 1.04]
0.95 [0.79, 1.09]
0.90 [0.77, 1.05]
N/A
N/A
0.96 (0.39)
0.89 (0.24)
0.22
...Missing; n (%)
52,877 (56.9%)
12,079 (56.6%)
92,778 (93.7%)
25,344 (94.2%)
N/A
N/A
145,655 (75.9%)
37,423 (77.6%)
-0.04
Lab result number- HDL level (mg/dl) mean (only =<5000 
included) 
                                          33,867                                              8,008                                              6,237                                              1,506 
N/A
N/A                                           40,104                                              9,514 
...mean (sd)
46.39 (13.51)
44.61 (12.78)
44.36 (39.28)
42.76 (13.63)
N/A
N/A
46.07 (19.85)
44.32 (12.92)
0.10
...median [IQR]
44.00 [37.00, 53.50]
43.00 [36.00, 52.00]
43.00 [35.50, 52.00]
42.00 [35.00, 50.00]
N/A
N/A
43.84 (19.85)
42.84 (12.92)
0.06
...Missing; n (%)
59,106 (63.6%)
13,338 (62.5%)
92,738 (93.7%)
25,404 (94.4%)
N/A
N/A
151,844 (79.1%)
38,742 (80.3%)
-0.03
Lab result number- LDL level (mg/dl) mean (only =<5000 
included) 
                                          34,168                                              8,115                                              5,889                                              1,378 
N/A
N/A                                           40,057                                              9,493 
...mean (sd)
85.70 (38.18)
83.53 (38.95)
87.52 (42.90)
85.68 (40.86)
N/A
N/A
85.97 (38.91)
83.84 (39.23)
0.05
...median [IQR]
83.00 [62.00, 107.00]
81.50 [60.50, 105.00]
86.00 [64.00, 112.00]
85.00 [62.00, 109.00]
N/A
N/A
83.44 (38.91)
82.01 (39.23)
0.04
...Missing; n (%)
58,805 (63.2%)
13,231 (62.0%)
93,086 (94.1%)
25,532 (94.9%)
N/A
N/A
151,891 (79.1%)
38,763 (80.3%)
-0.03
Lab result number- Total cholesterol (mg/dl) mean (only 
=<5000 included) 
                                          34,315                                              8,162                                              6,246                                              1,518 
N/A
N/A                                           40,561                                              9,680 
...mean (sd)
171.23 (44.49)
171.77 (46.18)
171.78 (54.30)
171.14 (48.01)
N/A
N/A
171.31 (46.14)
171.67 (46.47)
-0.01
...median [IQR]
165.00 [141.00, 195.00]
166.00 [141.00, 195.00]
169.29 [143.50, 200.00]
169.00 [143.00, 196.00]
N/A
N/A
165.66 (46.14)
166.47 (46.47)
-0.02
...Missing; n (%)
58,658 (63.1%)
13,184 (61.8%)
92,729 (93.7%)
25,392 (94.4%)
N/A
N/A
151,387 (78.9%)
38,576 (79.9%)
-0.02
Table 1

Lab result number- Triglyceride level (mg/dl) mean (only 
=<5000 included) 
                                          34,065                                              8,121                                              6,184                                              1,493 
N/A
N/A                                           40,249                                              9,614 
...mean (sd)
181.59 (137.93)
200.66 (176.08)
183.77 (164.61)
203.24 (187.27)
N/A
N/A
181.92 (142.36)
201.06 (177.87)
-0.12
...median [IQR]
151.00 [108.00, 214.00]
161.00 [114.00, 232.00]
148.00 [103.00, 217.50]
162.50 [112.00, 237.00]
N/A
N/A
150.54 (142.36)
161.23 (177.87)
-0.07
...Missing; n (%)
58,908 (63.4%)
13,225 (62.0%)
92,791 (93.8%)
25,417 (94.5%)
N/A
N/A
151,699 (79.0%)
38,642 (80.1%)
-0.03
Lab result number- Hemoglobin mean (only >0 included)
                                          27,271                                              5,946                                              4,588                                              1,015 
N/A
N/A                                           31,859                                              6,961 
...mean (sd)
13.46 (1.61)
14.01 (1.56)
12,956.08 (338,258.30)
2,982.84 (19,853.45)
N/A
N/A
1877.32 (128356.31)
446.90 (7579.01)
0.02
...median [IQR]
13.50 [12.40, 14.60]
14.05 [12.90, 15.05]
13.60 [12.50, 14.75]
14.00 [12.90, 15.00]
N/A
N/A
#VALUE!
#VALUE!
#VALUE!
...Missing; n (%)
65,702 (70.7%)
15,400 (72.1%)
94,387 (95.4%)
25,895 (96.2%)
N/A
N/A
160,089 (83.4%)
41,295 (85.6%)
-0.06
Lab result number- Serum sodium mean (only > 90 and < 
190 included)
                                          39,270                                              9,104                                              6,401                                              1,563 
N/A
N/A                                           45,671                                           10,667 
...mean (sd)
139.43 (2.75)
139.23 (2.68)
138.97 (2.59)
138.92 (2.40)
N/A
N/A
139.37 (2.73)
139.18 (2.64)
0.07
...median [IQR]
139.50 [138.00, 141.00]
139.00 [138.00, 141.00]
139.00 [137.00, 141.00]
139.00 [137.50, 140.25]
N/A
N/A
139.43 (2.73)
139.00 (2.64)
0.16
...Missing; n (%)
53,703 (57.8%)
12,242 (57.4%)
92,574 (93.5%)
25,347 (94.2%)
N/A
N/A
146,277 (76.2%)
37,589 (77.9%)
-0.04
Lab result number- Albumin mean (only >0 and <=10 
included)
                                          36,671                                              8,549                                              5,603                                              1,329 
N/A
N/A                                           42,274                                              9,878 
...mean (sd)
4.26 (0.31)
4.30 (0.30)
4.09 (0.76)
4.16 (0.66)
N/A
N/A
4.24 (0.40)
4.28 (0.37)
-0.10
...median [IQR]
4.30 [4.10, 4.50]
4.30 [4.10, 4.50]
4.20 [4.00, 4.40]
4.25 [4.00, 4.50]
N/A
N/A
4.29 (0.40)
4.29 (0.37)
0.00
...Missing; n (%)
56,302 (60.6%)
12,797 (60.0%)
93,372 (94.3%)
25,581 (95.1%)
N/A
N/A
149,674 (78.0%)
38,378 (79.5%)
-0.04
Lab result number- Glucose (fasting or random) mean 
(only 10-1000 included)
                                          39,234                                              9,095                                              6,390                                              1,544 
N/A
N/A                                           45,624                                           10,639 
...mean (sd)
173.67 (69.39)
181.41 (70.12)
179.40 (72.02)
180.71 (67.24)
N/A
N/A
174.47 (69.77)
181.31 (69.71)
-0.10
...median [IQR]
158.00 [126.67, 203.00]
166.50 [132.00, 216.00]
162.00 [130.00, 211.50]
167.00 [133.00, 216.00]
N/A
N/A
158.56 (69.77)
166.57 (69.71)
-0.11
...Missing; n (%)
53,739 (57.8%)
12,251 (57.4%)
92,585 (93.5%)
25,366 (94.3%)
N/A
N/A
146,324 (76.2%)
37,617 (78.0%)
-0.04
Lab result number- Potassium mean (only 1-7 included)
                                          40,119                                              9,278                                              6,414                                              1,521 
N/A
N/A                                           46,533                                           10,799 
...mean (sd)
4.47 (0.44)
4.45 (0.41)
4.33 (0.46)
4.36 (0.43)
N/A
N/A
4.45 (0.44)
4.44 (0.41)
0.02
...median [IQR]
4.45 [4.20, 4.70]
4.40 [4.20, 4.70]
4.30 [4.00, 4.60]
4.37 [4.10, 4.60]
N/A
N/A
4.43 (0.44)
4.40 (0.41)
0.07
...Missing; n (%)
52,854 (56.8%)
12,068 (56.5%)
92,561 (93.5%)
25,389 (94.3%)
N/A
N/A
145,415 (75.8%)
37,457 (77.6%)
-0.04
Comorbidity Scores
CCI (180 days)- ICD9 and ICD10 
...mean (sd)
2.56 (1.72)
2.09 (1.29)
1.87 (1.28)
1.67 (0.99)
2.72 (1.83)
2.35 (1.49)
2.50 (1.70)
2.06 (1.30)
0.29
...median [IQR]
2.00 [1.00, 3.00]
2.00 [1.00, 2.00]
1.00 [1.00, 2.00]
1.00 [1.00, 2.00]
2.00 [1.00, 4.00]
2.00 [1.00, 3.00]
1.78 (1.70)
1.68 (1.30)
0.07
Frailty Score: Qualitative Version 365 days as Categories, 
v1
...0; n (%)
57,374 (61.7%)
14,082 (66.0%)
54,311 (54.9%)
14,474 (53.8%)
105,245 (40.7%)
16,251 (46.3%)
216,930 (48.1%)
44,807 (53.7%)
-0.11
...1 to 2; n (%)
26,259 (28.2%)
5,640 (26.4%)
34,281 (34.6%)
10,034 (37.3%)
92,632 (35.8%)
12,243 (34.9%)
153,172 (34.0%)
27,917 (33.5%)
0.01
...3 or more; n (%)
9,340 (10.0%)
1,624 (7.6%)
10,383 (10.5%)
2,402 (8.9%)
60,917 (23.5%)
6,621 (18.9%)
80,640 (17.9%)
10,647 (12.8%)
0.14
Frailty Score: Empirical Version 365 days as Categories, 
...< 0.12908; n (%)
25,893 (27.9%)
7,492 (35.1%)
29,844 (30.2%)
8,892 (33.0%)
33,014 (12.8%)
5,571 (15.9%)
88,751 (19.7%)
21,955 (26.3%)
-0.16
...0.12908 - 0.1631167; n (%)
32,822 (35.3%)
8,051 (37.7%)
37,569 (38.0%)
10,669 (39.6%)
72,707 (28.1%)
11,082 (31.6%)
143,098 (31.7%)
29,802 (35.7%)
-0.08
...>= 0.1631167; n (%)
34,258 (36.8%)
5,803 (27.2%)
31,562 (31.9%)
7,349 (27.3%)
153,073 (59.1%)
18,462 (52.6%)
218,893 (48.6%)
31,614 (37.9%)
0.22
Non-Frailty; n (%)
54,232 (58.3%)
12,377 (58.0%)
51,769 (52.3%)
14,430 (53.6%)
12,308 (4.8%)
1,622 (4.6%)
118,309 (26.2%)
28,429 (34.1%)
-0.17
Frailty Score (mean): Qualitative Version 365 days, v1
...mean (sd)
0.79 (1.40)
0.64 (1.17)
0.88 (1.36)
0.83 (1.20)
1.54 (1.93)
1.25 (1.64)
1.24 (1.72)
0.96 (1.40)
0.18
...median [IQR]
0.00 [0.00, 1.00]
0.00 [0.00, 1.00]
0.00 [0.00, 1.00]
0.00 [0.00, 1.00]
1.00 [0.00, 2.00]
1.00 [0.00, 2.00]
0.57 (1.72)
0.42 (1.40)
0.10
Frailty Score (mean): Empirical Version 365 days, 
...mean (sd)
0.16 (0.05)
0.15 (0.04)
0.15 (0.04)
0.14 (0.04)
0.19 (0.06)
0.18 (0.05)
0.18 (0.05)
0.16 (0.04)
0.44
...median [IQR]
0.15 [0.13, 0.18]
0.14 [0.12, 0.17]
0.14 [0.12, 0.17]
0.14 [0.12, 0.16]
0.17 [0.15, 0.22]
0.17 [0.14, 0.20]
0.16 (0.05)
0.15 (0.04)
0.22
Healthcare Utilization
Any hospitalization; n (%)
4,363 (4.7%)
515 (2.4%)
4,045 (4.1%)
559 (2.1%)
17,460 (6.7%)
1,265 (3.6%)
25,868 (5.7%)
2,339 (2.8%)
0.14
Any hospitalization within prior 30 days; n (%)
1,461 (1.6%)
85 (0.4%)
1,226 (1.2%)
80 (0.3%)
5,637 (2.2%)
209 (0.6%)
8,324 (1.8%)
374 (0.4%)
0.13
Any hospitalization during prior 31-180 days; n (%)
3,101 (3.3%)
434 (2.0%)
2,913 (2.9%)
482 (1.8%)
12,641 (4.9%)
1,083 (3.1%)
18,655 (4.1%)
1,999 (2.4%)
0.10
Endocrinologist Visit; n (%)
8,305 (8.9%)
3,857 (18.1%)
8,479 (8.6%)
5,166 (19.2%)
28,751 (11.1%)
6,793 (19.3%)
45,535 (10.1%)
15,816 (19.0%)
-0.25
Endocrinologist Visit (30 days prior); n (%)
5,443 (5.9%)
2,835 (13.3%)
5,738 (5.8%)
4,064 (15.1%)
18,611 (7.2%)
4,820 (13.7%)
29,792 (6.6%)
11,719 (14.1%)
-0.25
Endocrinologist Visit (31 to 180 days prior); n (%)
5,625 (6.1%)
2,733 (12.8%)
5,578 (5.6%)
3,673 (13.6%)
20,367 (7.9%)
5,233 (14.9%)
31,570 (7.0%)
11,639 (14.0%)
-0.23
Internal medicine/family medicine visits; n (%)
77,583 (83.4%)
15,326 (71.8%)
87,485 (88.4%)
23,433 (87.1%)
213,115 (82.3%)
28,985 (82.5%)
378,183 (83.9%)
67,744 (81.3%)
0.07
Internal medicine/family medicine visits (30 days prior) ; 
n (%)
59,224 (63.7%)
11,193 (52.4%)
66,816 (67.5%)
17,732 (65.9%)
155,670 (60.2%)
21,013 (59.8%)
281,710 (62.5%)
49,938 (59.9%)
0.05
Internal medicine/family medicine visits (31 to 180 days 
prior) ; n (%)
66,924 (72.0%)
13,192 (61.8%)
71,698 (72.4%)
19,673 (73.1%)
184,082 (71.1%)
25,511 (72.6%)
322,704 (71.6%)
58,376 (70.0%)
0.04
Cardiologist visit; n (%)
22,028 (23.7%)
4,060 (19.0%)
17,523 (17.7%)
4,413 (16.4%)
79,665 (30.8%)
9,926 (28.3%)
119,216 (26.4%)
18,399 (22.1%)
0.10
Number of Cardiologist visits (30 days prior); n (%)
7,462 (8.0%)
1,253 (5.9%)
5,922 (6.0%)
1,343 (5.0%)
27,234 (10.5%)
3,020 (8.6%)
40,618 (9.0%)
5,616 (6.7%)
0.09
Table 1

Number of Cardiologist visits (31 to 180 days prior); n (%)
18,520 (19.9%)
3,452 (16.2%)
14,636 (14.8%)
3,739 (13.9%)
68,179 (26.3%)
8,616 (24.5%)
101,335 (22.5%)
15,807 (19.0%)
0.09
Electrocardiogram ; n (%)
25,313 (27.2%)
4,791 (22.4%)
25,662 (25.9%)
6,067 (22.5%)
80,490 (31.1%)
9,794 (27.9%)
131,465 (29.2%)
20,652 (24.8%)
0.10
Use of glucose test strips; n (%)
3,407 (3.7%)
762 (3.6%)
3,506 (3.5%)
1,117 (4.2%)
8,264 (3.2%)
1,086 (3.1%)
15,177 (3.4%)
2,965 (3.6%)
-0.01
Dialysis; n (%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
000 (0.0%)
000 (0.0%)
#DIV/0!
Naive new user v8 ; n (%)
13,385 (14.4%)
1,888 (8.8%)
14,612 (14.8%)
1,995 (7.4%)
32,045 (12.4%)
1,925 (5.5%)
60,042 (13.3%)
5,808 (7.0%)
0.21
N antidiabetic drugs at index date  
...mean (sd)
2.23 (0.81)
2.42 (0.92)
2.23 (0.79)
2.46 (0.96)
2.21 (0.81)
2.47 (0.91)
2.22 (0.81)
2.45 (0.93)
-0.26
...median [IQR]
2.00 [2.00, 3.00]
2.00 [2.00, 3.00]
2.00 [2.00, 3.00]
2.00 [2.00, 3.00]
2.00 [2.00, 3.00]
2.00 [2.00, 3.00]
2.00 (0.81)
2.00 (0.93)
0.00
number of different/distinct medication prescriptions
...mean (sd)
10.02 (4.35)
10.15 (4.34)
9.12 (4.01)
10.05 (4.19)
9.97 (4.17)
10.43 (4.16)
9.79 (4.17)
10.24 (4.22)
-0.11
...median [IQR]
9.00 [7.00, 12.00]
9.00 [7.00, 12.00]
8.00 [6.00, 11.00]
9.00 [7.00, 12.00]
9.00 [7.00, 12.00]10.00 [8.00, 13.00]
8.78 (4.17)
9.42 (4.22)
-0.15
Number of Hospitalizations
...mean (sd)
0.05 (0.26)
0.03 (0.17)
0.04 (0.23)
0.02 (0.16)
0.08 (0.33)
0.04 (0.22)
0.07 (0.30)
0.03 (0.19)
0.16
...median [IQR]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 (0.30)
0.00 (0.19)
0.00
Number of hospital days
...mean (sd)
0.29 (2.21)
0.12 (0.98)
0.23 (1.60)
0.10 (0.85)
0.49 (2.90)
0.21 (1.65)
0.39 (2.53)
0.15 (1.28)
0.12
...median [IQR]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 (2.53)
0.00 (1.28)
0.00
Number of Emergency Department (ED) visits 
...mean (sd)
0.31 (0.96)
0.21 (0.75)
0.09 (0.93)
0.05 (0.78)
0.42 (1.19)
0.29 (1.02)
0.32 (1.09)
0.19 (0.88)
0.13
...median [IQR]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 (1.09)
0.00 (0.88)
0.00
Number of Office visits
...mean (sd)
4.32 (3.26)
4.23 (3.02)
4.09 (3.12)
4.26 (3.12)
4.81 (3.63)
4.99 (3.51)
4.55 (3.45)
4.56 (3.27)
0.00
...median [IQR]
4.00 [2.00, 6.00]
3.00 [2.00, 6.00]
3.00 [2.00, 5.00]
3.00 [2.00, 5.00]
4.00 [2.00, 6.00]
4.00 [3.00, 7.00]
3.78 (3.45)
3.42 (3.27)
0.11
Number of Endocrinologist visits
...mean (sd)
0.40 (2.04)
0.96 (3.30)
0.38 (1.98)
1.03 (3.44)
0.61 (2.93)
1.26 (4.60)
0.52 (2.58)
1.11 (3.94)
-0.18
...median [IQR]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 (2.58)
0.00 (3.94)
0.00
Number of internal medicine/family medicine visits
...mean (sd)
8.97 (12.35)
6.96 (10.66)
6.59 (7.92)
6.45 (7.85)
7.38 (9.52)
7.56 (9.83)
7.53 (9.86)
7.05 (9.47)
0.05
...median [IQR]
5.00 [2.00, 12.00]
4.00 [0.00, 9.00]
4.00 [2.00, 9.00]
4.00 [2.00, 9.00]
4.00 [2.00, 10.00] 5.00 [1.00, 10.00]
4.21 (9.86)
4.42 (9.47)
-0.02
Number of Cardiologist visits
...mean (sd)
1.01 (2.94)
0.76 (2.48)
0.70 (2.37)
0.62 (2.13)
1.49 (3.91)
1.33 (3.64)
1.22 (3.43)
0.95 (2.94)
0.08
...median [IQR]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 1.00]
0.00 [0.00, 1.00]
0.00 (3.43)
0.00 (2.94)
0.00
Number electrocardiograms received 
...mean (sd)
0.47 (1.08)
0.35 (0.85)
0.42 (0.97)
0.34 (0.79)
0.57 (1.17)
0.48 (1.04)
0.52 (1.11)
0.40 (0.92)
0.12
...median [IQR]
0.00 [0.00, 1.00]
0.00 [0.00, 0.00]
0.00 [0.00, 1.00]
0.00 [0.00, 0.00]
0.00 [0.00, 1.00]
0.00 [0.00, 1.00]
0.00 (1.11)
0.00 (0.92)
0.00
Number of HbA1c tests ordered
...mean (sd)
1.32 (0.89)
1.37 (0.87)
1.08 (0.87)
1.30 (0.87)
1.43 (0.84)
1.57 (0.81)
1.33 (0.86)
1.43 (0.85)
-0.12
...median [IQR]
1.00 [1.00, 2.00]
1.00 [1.00, 2.00]
1.00 [0.00, 2.00]
1.00 [1.00, 2.00]
1.00 [1.00, 2.00]
2.00 [1.00, 2.00]
1.00 (0.86)
1.42 (0.85)
-0.49
Number of glucose tests ordered
...mean (sd)
0.55 (3.99)
0.43 (1.17)
0.35 (1.05)
0.42 (1.12)
0.42 (1.04)
0.45 (1.08)
0.43 (2.04)
0.44 (1.12)
-0.01
...median [IQR]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 (2.04)
0.00 (1.12)
0.00
Number of lipid tests ordered
...mean (sd)
1.03 (0.93)
1.06 (0.95)
0.91 (1.21)
1.08 (1.23)
1.03 (0.81)
1.11 (0.82)
1.00 (0.94)
1.09 (1.00)
-0.09
...median [IQR]
1.00 [0.00, 1.00]
1.00 [0.00, 2.00]
1.00 [0.00, 1.00]
1.00 [0.00, 2.00]
1.00 [0.00, 1.00]
1.00 [1.00, 2.00]
1.00 (0.94)
1.00 (1.00)
0.00
Number of creatinine tests ordered
...mean (sd)
0.04 (0.28)
0.03 (0.22)
0.04 (0.26)
0.04 (0.24)
0.07 (0.32)
0.07 (0.33)
0.06 (0.30)
0.05 (0.28)
0.03
...median [IQR]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 (0.30)
0.00 (0.28)
0.00
Number of BUN tests ordered
...mean (sd)
0.03 (0.22)
0.02 (0.17)
0.03 (0.21)
0.02 (0.18)
0.04 (0.26)
0.04 (0.26)
0.04 (0.24)
0.03 (0.22)
0.04
...median [IQR]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 (0.24)
0.00 (0.22)
0.00
Number of tests for microalbuminuria
...mean (sd)
0.85 (1.20)
0.84 (1.16)
0.64 (1.04)
0.76 (1.11)
0.50 (0.72)
0.53 (0.72)
0.60 (0.91)
0.68 (0.98)
-0.08
...median [IQR]
0.00 [0.00, 2.00]
0.00 [0.00, 2.00]
0.00 [0.00, 1.00]
0.00 [0.00, 2.00]
0.00 [0.00, 1.00]
0.00 [0.00, 1.00]
0.00 (0.91)
0.00 (0.98)
0.00
Total N distinct ICD9/ICD10 diagnoses at the 3rd digit 
level 
...mean (sd)
6.16 (6.85)
5.46 (5.86)
2.67 (4.07)
2.01 (3.26)
5.84 (7.61)
5.73 (6.80)
5.21 (6.82)
4.46 (5.63)
0.12
...median [IQR]
5.00 [0.00, 9.00]
5.00 [0.00, 8.00]
0.00 [0.00, 4.00]
0.00 [0.00, 4.00]
4.00 [0.00, 9.00]
4.00 [0.00, 9.00]
3.33 (6.82)
2.96 (5.63)
0.06
Use of thiazide; n (%)
13,054 (14.0%)
2,752 (12.9%)
12,759 (12.9%)
3,416 (12.7%)
39,231 (15.2%)
5,305 (15.1%)
65,044 (14.4%)
11,473 (13.8%)
0.02
Use of beta blockers; n (%)
39,244 (42.2%)
7,904 (37.0%)
37,716 (38.1%)
9,582 (35.6%)
131,430 (50.8%)
17,160 (48.9%)
208,390 (46.2%)
34,646 (41.6%)
0.09
Use of calcium channel blockers; n (%)
32,362 (34.8%)
6,181 (29.0%)
31,378 (31.7%)
7,884 (29.3%)
97,784 (37.8%)
11,964 (34.1%)
161,524 (35.8%)
26,029 (31.2%)
0.10
Table 1

Variable
Reference- DPP4i
Exposure- Canagliflozin
Reference- DPP4i
Exposure- Canagliflozin
Reference- DPP4i
Exposure- Canagliflozin
Reference- DPP4i
Exposure- Canagliflozin
St. Diff.
Number of patients
19532
19532
23168
23168
33401
33401                                           76,101                                           76,101 
Age
...mean (sd)
62.47 (8.28)
62.59 (7.93)
59.39 (7.08)
59.50 (6.58)
71.02 (5.32)
71.06 (5.19)
65.28 (6.73)
65.37 (6.41)
-0.01
...median [IQR]
62.00 [55.00, 68.00]
62.00 [56.00, 68.00]
58.00 [54.00, 63.00]
59.00 [55.00, 63.00]
70.00 [67.00, 74.00]
70.00 [67.00, 74.00]
64.29 (6.73)
64.60 (6.41)
-0.05
Age categories 
...18 - 54; n (%)
4,084 (20.9%)
3,519 (18.0%)
6,340 (27.4%)
5,719 (24.7%)
0 (0.0%)
0 (0.0%)
10,424 (13.7%)
9,238 (12.1%)
0.05
...55 - 64; n (%)
7,394 (37.9%)
8,104 (41.5%)
12,899 (55.7%)
13,461 (58.1%)
424 (1.3%)
370 (1.1%)
20,717 (27.2%)
21,935 (28.8%)
-0.04
...65 - 74; n (%)
6,444 (33.0%)
6,418 (32.9%)
2,941 (12.7%)
3,259 (14.1%)
25,613 (76.7%)
25,764 (77.1%)
34,998 (46.0%)
35,441 (46.6%)
-0.01
...>= 75; n (%)
1,610 (8.2%)
1,491 (7.6%)
988 (4.3%)
729 (3.1%)
7,364 (22.0%)
7,267 (21.8%)
9,962 (13.1%)
9,487 (12.5%)
0.02
Gender 
...Males; n (%)
10,959 (56.1%)
10,973 (56.2%)
12,925 (55.8%)
12,966 (56.0%)
16,977 (50.8%)
17,007 (50.9%)
40,861 (53.7%)
40,946 (53.8%)
0.00
...Females; n (%)
8,573 (43.9%)
8,559 (43.8%)
10,243 (44.2%)
10,202 (44.0%)
16,424 (49.2%)
16,394 (49.1%)
35,240 (46.3%)
35,155 (46.2%)
0.00
Race 
...White; n (%)
N/A
N/A
N/A
N/A
27,463 (82.2%)
27,436 (82.1%)
27,463 (82.2%)
27,436 (82.1%)
0.00
...Black; n (%)
N/A
N/A
N/A
N/A
2,664 (8.0%)
2,721 (8.1%)
2,664 (8.0%)
2,721 (8.1%)
0.00
...Asian; n (%)
N/A
N/A
N/A
N/A
905 (2.7%)
893 (2.7%)
905 (2.7%)
893 (2.7%)
0.00
...Hispanic; n (%)
N/A
N/A
N/A
N/A
970 (2.9%)
935 (2.8%)
970 (2.9%)
935 (2.8%)
0.01
...North American Native; n (%)
N/A
N/A
N/A
N/A
118 (0.4%)
125 (0.4%)
118 (0.4%)
125 (0.4%)
0.00
...Other/Unknown; n (%)
N/A
N/A
N/A
N/A
1,281 (3.8%)
1,291 (3.9%)
1,281 (3.8%)
1,291 (3.9%)
-0.01
Region   (lumping missing&other category with 
West)
...Northeast; n (%)
1,586 (8.1%)
1,623 (8.3%)
3,890 (16.8%)
3,981 (17.2%)
5,552 (16.6%)
5,609 (16.8%)
11,028 (14.5%)
11,213 (14.7%)
-0.01
...South; n (%)
10,537 (53.9%)
10,459 (53.5%)
4,391 (19.0%)
4,343 (18.7%)
15,091 (45.2%)
15,024 (45.0%)
30,019 (39.4%)
29,826 (39.2%)
0.00
...Midwest; n (%)
4,118 (21.1%)
4,140 (21.2%)
12,382 (53.4%)
12,389 (53.5%)
7,584 (22.7%)
7,572 (22.7%)
24,084 (31.6%)
24,101 (31.7%)
0.00
...West; n (%)
3,291 (16.8%)
3,310 (16.9%)
2,258 (9.7%)
2,209 (9.5%)
5,174 (15.5%)
5,196 (15.6%)
10,723 (14.1%)
10,715 (14.1%)
0.00
...Unknown+missing; n (%)
N/A
N/A
247 (1.1%)
246 (1.1%)
N/A
N/A
247 (1.1%)
246 (1.1%)
0.00
CV Covariates
Ischemic heart disease; n (%)
2,850 (14.6%)
2,863 (14.7%)
2,777 (12.0%)
2,846 (12.3%)
8,538 (25.6%)
8,401 (25.2%)
14,165 (18.6%)
14,110 (18.5%)
0.00
Acute MI; n (%)
49 (0.3%)
53 (0.3%)
65 (0.3%)
60 (0.3%)
116 (0.3%)
118 (0.4%)
230 (0.3%)
231 (0.3%)
0.00
ACS/unstable angina; n (%)
93 (0.5%)
87 (0.4%)
96 (0.4%)
86 (0.4%)
170 (0.5%)
172 (0.5%)
359 (0.5%)
345 (0.5%)
0.00
Old MI; n (%)
334 (1.7%)
331 (1.7%)
194 (0.8%)
182 (0.8%)
855 (2.6%)
839 (2.5%)
1,383 (1.8%)
1,352 (1.8%)
0.00
Stable angina; n (%)
402 (2.1%)
407 (2.1%)
311 (1.3%)
310 (1.3%)
988 (3.0%)
954 (2.9%)
1,701 (2.2%)
1,671 (2.2%)
0.00
Coronary atherosclerosis and other forms of chronic 
ischemic heart disease; n (%)
2,663 (13.6%)
2,698 (13.8%)
2,638 (11.4%)
2,695 (11.6%)
8,217 (24.6%)
8,074 (24.2%)
13,518 (17.8%)
13,467 (17.7%)
0.00
Other atherosclerosis with ICD10  ; n (%)
88 (0.5%)
85 (0.4%)
113 (0.5%)
130 (0.6%)
339 (1.0%)
384 (1.1%)
540 (0.7%)
599 (0.8%)
-0.01
Previous cardiac procedure (CABG or PTCA or Stent) ; 
n (%)
25 (0.1%)
25 (0.1%)
37 (0.2%)
32 (0.1%)
40 (0.1%)
67 (0.2%)
102 (0.1%)
124 (0.2%)
-0.03
History of CABG or PTCA; n (%)
596 (3.1%)
600 (3.1%)
352 (1.5%)
340 (1.5%)
2,019 (6.0%)
1,992 (6.0%)
2,967 (3.9%)
2,932 (3.9%)
0.00
Any stroke; n (%)
462 (2.4%)
489 (2.5%)
450 (1.9%)
451 (1.9%)
1,806 (5.4%)
1,754 (5.3%)
2,718 (3.6%)
2,694 (3.5%)
0.01
Ischemic stroke (w and w/o mention of cerebral 
infarction); n (%)
460 (2.4%)
487 (2.5%)
448 (1.9%)
448 (1.9%)
1,798 (5.4%)
1,749 (5.2%)
2,706 (3.6%)
2,684 (3.5%)
0.01
Hemorrhagic stroke; n (%)
4 (0.0%)
5 (0.0%)
3 (0.0%)
4 (0.0%)
**
**
**
**
**
TIA; n (%)
48 (0.2%)
59 (0.3%)
46 (0.2%)
50 (0.2%)
171 (0.5%)
170 (0.5%)
265 (0.3%)
279 (0.4%)
-0.02
Other cerebrovascular disease; n (%)
138 (0.7%)
130 (0.7%)
95 (0.4%)
90 (0.4%)
349 (1.0%)
341 (1.0%)
582 (0.8%)
561 (0.7%)
0.01
Late effects of cerebrovascular disease; n (%)
100 (0.5%)
92 (0.5%)
62 (0.3%)
61 (0.3%)
271 (0.8%)
255 (0.8%)
433 (0.6%)
408 (0.5%)
0.01
Cerebrovascular procedure; n (%)
3 (0.0%)
6 (0.0%)
6 (0.0%)
3 (0.0%)
13 (0.0%)
17 (0.1%)
022 (0.0%)
026 (0.0%)
#DIV/0!
Heart failure (CHF); n (%)
756 (3.9%)
780 (4.0%)
482 (2.1%)
496 (2.1%)
2,270 (6.8%)
2,224 (6.7%)
3,508 (4.6%)
3,500 (4.6%)
0.00
Peripheral Vascular Disease (PVD) or PVD Surgery ; n 
(%)
858 (4.4%)
863 (4.4%)
590 (2.5%)
615 (2.7%)
2,598 (7.8%)
2,579 (7.7%)
4,046 (5.3%)
4,057 (5.3%)
0.00
Atrial fibrillation; n (%)
854 (4.4%)
843 (4.3%)
704 (3.0%)
711 (3.1%)
2,914 (8.7%)
2,860 (8.6%)
4,472 (5.9%)
4,414 (5.8%)
0.00
Other cardiac dysrhythmia; n (%)
1,067 (5.5%)
1,057 (5.4%)
794 (3.4%)
788 (3.4%)
3,293 (9.9%)
3,214 (9.6%)
5,154 (6.8%)
5,059 (6.6%)
0.01
Cardiac conduction disorders; n (%)
270 (1.4%)
270 (1.4%)
227 (1.0%)
220 (0.9%)
864 (2.6%)
912 (2.7%)
1,361 (1.8%)
1,402 (1.8%)
0.00
Other CVD; n (%)
1,212 (6.2%)
1,194 (6.1%)
1,109 (4.8%)
1,153 (5.0%)
3,635 (10.9%)
3,614 (10.8%)
5,956 (7.8%)
5,961 (7.8%)
0.00
Diabetes-related complications
Diabetic retinopathy; n (%)
1,161 (5.9%)
1,147 (5.9%)
909 (3.9%)
935 (4.0%)
2,514 (7.5%)
2,514 (7.5%)
4,584 (6.0%)
4,596 (6.0%)
0.00
Diabetes with other ophthalmic manifestations; n 
(%)
120 (0.6%)
136 (0.7%)
561 (2.4%)
567 (2.4%)
879 (2.6%)
924 (2.8%)
1,560 (2.0%)
1,627 (2.1%)
-0.01
Retinal detachment, vitreous hemorrhage, 
vitrectomy; n (%)
70 (0.4%)
73 (0.4%)
82 (0.4%)
69 (0.3%)
153 (0.5%)
140 (0.4%)
305 (0.4%)
282 (0.4%)
0.00
Retinal laser coagulation therapy; n (%)
115 (0.6%)
103 (0.5%)
145 (0.6%)
122 (0.5%)
222 (0.7%)
209 (0.6%)
482 (0.6%)
434 (0.6%)
0.00
Occurrence of Diabetic Neuropathy  ; n (%)
3,305 (16.9%)
3,391 (17.4%)
2,498 (10.8%)
2,503 (10.8%)
6,540 (19.6%)
6,535 (19.6%)
12,343 (16.2%)
12,429 (16.3%)
0.00
Optum
 PS-matched
MarketScan
Medicare
POOLED
Table 1

Occurrence of diabetic nephropathy  with ICD10 ; n 
(%)
1,981 (10.1%)
2,014 (10.3%)
1,299 (5.6%)
1,282 (5.5%)
2,783 (8.3%)
2,769 (8.3%)
6,063 (8.0%)
6,065 (8.0%)
0.00
Hypoglycemia ; n (%)
403 (2.1%)
414 (2.1%)
517 (2.2%)
518 (2.2%)
736 (2.2%)
769 (2.3%)
1,656 (2.2%)
1,701 (2.2%)
0.00
Hyperglycemia; n (%)
650 (3.3%)
631 (3.2%)
659 (2.8%)
626 (2.7%)
1,112 (3.3%)
1,107 (3.3%)
2,421 (3.2%)
2,364 (3.1%)
0.01
Disorders of fluid electrolyte and acid-base balance; n 
(%)
653 (3.3%)
647 (3.3%)
501 (2.2%)
511 (2.2%)
1,420 (4.3%)
1,381 (4.1%)
2,574 (3.4%)
2,539 (3.3%)
0.01
Diabetic ketoacidosis; n (%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
000 (0.0%)
000 (0.0%)
#DIV/0!
Hyperosmolar hyperglycemic nonketotic syndrome 
(HONK); n (%)
86 (0.4%)
88 (0.5%)
80 (0.3%)
81 (0.3%)
163 (0.5%)
158 (0.5%)
329 (0.4%)
327 (0.4%)
0.00
Diabetes with peripheral circulatory disorders with 
ICD-10  ; n (%)
947 (4.8%)
954 (4.9%)
586 (2.5%)
581 (2.5%)
1,982 (5.9%)
1,982 (5.9%)
3,515 (4.6%)
3,517 (4.6%)
0.00
Diabetic Foot; n (%)
261 (1.3%)
257 (1.3%)
275 (1.2%)
275 (1.2%)
663 (2.0%)
679 (2.0%)
1,199 (1.6%)
1,211 (1.6%)
0.00
Gangrene ; n (%)
19 (0.1%)
19 (0.1%)
8 (0.0%)
9 (0.0%)
36 (0.1%)
27 (0.1%)
063 (0.1%)
055 (0.1%)
0.00
Lower extremity amputation; n (%)
67 (0.3%)
58 (0.3%)
30 (0.1%)
28 (0.1%)
100 (0.3%)
106 (0.3%)
197 (0.3%)
192 (0.3%)
0.00
Osteomyelitis; n (%)
54 (0.3%)
49 (0.3%)
58 (0.3%)
53 (0.2%)
109 (0.3%)
97 (0.3%)
221 (0.3%)
199 (0.3%)
0.00
Skin infections ; n (%)
890 (4.6%)
893 (4.6%)
949 (4.1%)
989 (4.3%)
1,854 (5.6%)
1,877 (5.6%)
3,693 (4.9%)
3,759 (4.9%)
0.00
Erectile dysfunction; n (%)
689 (3.5%)
695 (3.6%)
617 (2.7%)
635 (2.7%)
1,022 (3.1%)
1,015 (3.0%)
2,328 (3.1%)
2,345 (3.1%)
0.00
Diabetes with unspecified complication; n (%)
1,023 (5.2%)
990 (5.1%)
1,050 (4.5%)
991 (4.3%)
1,780 (5.3%)
1,745 (5.2%)
3,853 (5.1%)
3,726 (4.9%)
0.01
Diabetes mellitus without mention of complications; 
n (%)
16,531 (84.6%)
16,497 (84.5%)
21,189 (91.5%)
21,263 (91.8%)
30,549 (91.5%)
30,535 (91.4%)
68,269 (89.7%)
68,295 (89.7%)
0.00
Hypertension: 1 inpatient or 2 outpatient claims 
within 365 days; n (%)
17,868 (91.5%)
17,907 (91.7%)
20,220 (87.3%)
20,239 (87.4%)
31,932 (95.6%)
31,930 (95.6%)
70,020 (92.0%)
70,076 (92.1%)
0.00
Hyperlipidemia ; n (%)
14,994 (76.8%)
15,046 (77.0%)
17,333 (74.8%)
17,386 (75.0%)
27,362 (81.9%)
27,400 (82.0%)
59,689 (78.4%)
59,832 (78.6%)
0.00
Edema; n (%)
914 (4.7%)
894 (4.6%)
739 (3.2%)
756 (3.3%)
2,395 (7.2%)
2,412 (7.2%)
4,048 (5.3%)
4,062 (5.3%)
0.00
Renal Dysfunction (non-diabetic) ; n (%)
1,939 (9.9%)
2,024 (10.4%)
1,275 (5.5%)
1,284 (5.5%)
4,135 (12.4%)
4,083 (12.2%)
7,349 (9.7%)
7,391 (9.7%)
0.00
Occurrence of acute renal disease ; n (%)
164 (0.8%)
169 (0.9%)
122 (0.5%)
119 (0.5%)
366 (1.1%)
368 (1.1%)
652 (0.9%)
656 (0.9%)
0.00
Occurrence of chronic renal insufficiency; n (%)
1,542 (7.9%)
1,672 (8.6%)
940 (4.1%)
937 (4.0%)
3,348 (10.0%)
3,378 (10.1%)
5,830 (7.7%)
5,987 (7.9%)
-0.01
Chronic kidney disease ; n (%)
1,464 (7.5%)
1,563 (8.0%)
838 (3.6%)
810 (3.5%)
3,157 (9.5%)
3,109 (9.3%)
5,459 (7.2%)
5,482 (7.2%)
0.00
CKD Stage 3-4; n (%)
753 (3.9%)
822 (4.2%)
430 (1.9%)
420 (1.8%)
1,843 (5.5%)
1,828 (5.5%)
3,026 (4.0%)
3,070 (4.0%)
0.00
Occurrence of hypertensive nephropathy; n (%)
655 (3.4%)
658 (3.4%)
335 (1.4%)
334 (1.4%)
1,133 (3.4%)
1,149 (3.4%)
2,123 (2.8%)
2,141 (2.8%)
0.00
Occurrence of miscellaneous renal insufficiency ; n 
(%)
390 (2.0%)
404 (2.1%)
337 (1.5%)
368 (1.6%)
1,135 (3.4%)
1,135 (3.4%)
1,862 (2.4%)
1,907 (2.5%)
-0.01
Glaucoma or cataracts ; n (%)
3,316 (17.0%)
3,314 (17.0%)
3,168 (13.7%)
3,115 (13.4%)
9,148 (27.4%)
9,098 (27.2%)
15,632 (20.5%)
15,527 (20.4%)
0.00
Cellulitis or abscess of toe; n (%)
197 (1.0%)
179 (0.9%)
146 (0.6%)
144 (0.6%)
346 (1.0%)
367 (1.1%)
689 (0.9%)
690 (0.9%)
0.00
Foot ulcer; n (%)
253 (1.3%)
241 (1.2%)
271 (1.2%)
275 (1.2%)
657 (2.0%)
672 (2.0%)
1,181 (1.6%)
1,188 (1.6%)
0.00
Bladder stones; n (%)
15 (0.1%)
11 (0.1%)
10 (0.0%)
10 (0.0%)
30 (0.1%)
49 (0.1%)
055 (0.1%)
070 (0.1%)
0.00
Kidney stones; n (%)
312 (1.6%)
305 (1.6%)
406 (1.8%)
406 (1.8%)
692 (2.1%)
721 (2.2%)
1,410 (1.9%)
1,432 (1.9%)
0.00
Urinary tract infections (UTIs); n (%)
978 (5.0%)
975 (5.0%)
961 (4.1%)
933 (4.0%)
2,735 (8.2%)
2,708 (8.1%)
4,674 (6.1%)
4,616 (6.1%)
0.00
Dipstick urinalysis; n (%)
6,234 (31.9%)
5,989 (30.7%)
7,326 (31.6%)
7,016 (30.3%)
11,825 (35.4%)
11,790 (35.3%)
25,385 (33.4%)
24,795 (32.6%)
0.02
Non-dipstick urinalysis; n (%)
8,743 (44.8%)
8,830 (45.2%)
9,618 (41.5%)
9,590 (41.4%)
15,296 (45.8%)
15,274 (45.7%)
33,657 (44.2%)
33,694 (44.3%)
0.00
Urine function test; n (%)
279 (1.4%)
256 (1.3%)
339 (1.5%)
306 (1.3%)
1,002 (3.0%)
850 (2.5%)
1,620 (2.1%)
1,412 (1.9%)
0.01
Cytology; n (%)
79 (0.4%)
80 (0.4%)
129 (0.6%)
116 (0.5%)
229 (0.7%)
206 (0.6%)
437 (0.6%)
402 (0.5%)
0.01
Cystos; n (%)
127 (0.7%)
123 (0.6%)
151 (0.7%)
164 (0.7%)
356 (1.1%)
317 (0.9%)
634 (0.8%)
604 (0.8%)
0.00
Other Covariates
Liver disease; n (%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
000 (0.0%)
000 (0.0%)
#DIV/0!
Osteoarthritis; n (%)
1,991 (10.2%)
2,018 (10.3%)
1,579 (6.8%)
1,656 (7.1%)
5,413 (16.2%)
5,337 (16.0%)
8,983 (11.8%)
9,011 (11.8%)
0.00
Other arthritis, arthropathies and musculoskeletal 
pain; n (%)
5,293 (27.1%)
5,257 (26.9%)
5,487 (23.7%)
5,503 (23.8%)
11,402 (34.1%)
11,358 (34.0%)
22,182 (29.1%)
22,118 (29.1%)
0.00
Dorsopathies; n (%)
3,513 (18.0%)
3,473 (17.8%)
3,457 (14.9%)
3,478 (15.0%)
7,367 (22.1%)
7,314 (21.9%)
14,337 (18.8%)
14,265 (18.7%)
0.00
Fractures; n (%)
313 (1.6%)
304 (1.6%)
351 (1.5%)
323 (1.4%)
758 (2.3%)
740 (2.2%)
1,422 (1.9%)
1,367 (1.8%)
0.01
Falls ; n (%)
325 (1.7%)
329 (1.7%)
125 (0.5%)
121 (0.5%)
729 (2.2%)
691 (2.1%)
1,179 (1.5%)
1,141 (1.5%)
0.00
Osteoporosis; n (%)
484 (2.5%)
496 (2.5%)
262 (1.1%)
266 (1.1%)
1,735 (5.2%)
1,739 (5.2%)
2,481 (3.3%)
2,501 (3.3%)
0.00
Hyperthyroidism; n (%)
132 (0.7%)
102 (0.5%)
131 (0.6%)
90 (0.4%)
270 (0.8%)
238 (0.7%)
533 (0.7%)
430 (0.6%)
0.01
Hypothyroidism ; n (%)
2,755 (14.1%)
2,732 (14.0%)
2,713 (11.7%)
2,686 (11.6%)
4,012 (12.0%)
3,970 (11.9%)
9,480 (12.5%)
9,388 (12.3%)
0.01
Other disorders of thyroid gland ; n (%)
735 (3.8%)
666 (3.4%)
780 (3.4%)
775 (3.3%)
1,483 (4.4%)
1,324 (4.0%)
2,998 (3.9%)
2,765 (3.6%)
0.02
Depression; n (%)
1,318 (6.7%)
1,347 (6.9%)
1,367 (5.9%)
1,317 (5.7%)
2,756 (8.3%)
2,733 (8.2%)
5,441 (7.1%)
5,397 (7.1%)
0.00
Anxiety; n (%)
1,279 (6.5%)
1,247 (6.4%)
1,075 (4.6%)
1,056 (4.6%)
2,282 (6.8%)
2,256 (6.8%)
4,636 (6.1%)
4,559 (6.0%)
0.00
Sleep_Disorder; n (%)
1,356 (6.9%)
1,364 (7.0%)
2,268 (9.8%)
2,344 (10.1%)
2,703 (8.1%)
2,706 (8.1%)
6,327 (8.3%)
6,414 (8.4%)
0.00
Dementia; n (%)
200 (1.0%)
195 (1.0%)
110 (0.5%)
109 (0.5%)
913 (2.7%)
893 (2.7%)
1,223 (1.6%)
1,197 (1.6%)
0.00
Delirium; n (%)
45 (0.2%)
55 (0.3%)
28 (0.1%)
29 (0.1%)
195 (0.6%)
179 (0.5%)
268 (0.4%)
263 (0.3%)
0.02
Psychosis; n (%)
89 (0.5%)
87 (0.4%)
44 (0.2%)
47 (0.2%)
255 (0.8%)
255 (0.8%)
388 (0.5%)
389 (0.5%)
0.00
Obesity; n (%)
5,168 (26.5%)
5,115 (26.2%)
4,206 (18.2%)
4,246 (18.3%)
6,410 (19.2%)
6,322 (18.9%)
15,784 (20.7%)
15,683 (20.6%)
0.00
Overweight; n (%)
1,026 (5.3%)
1,024 (5.2%)
576 (2.5%)
522 (2.3%)
1,239 (3.7%)
1,189 (3.6%)
2,841 (3.7%)
2,735 (3.6%)
0.01
Smoking; n (%)
1,624 (8.3%)
1,622 (8.3%)
1,219 (5.3%)
1,174 (5.1%)
3,528 (10.6%)
3,585 (10.7%)
6,371 (8.4%)
6,381 (8.4%)
0.00
Alcohol abuse or dependence; n (%)
3 (0.0%)
2 (0.0%)
6 (0.0%)
5 (0.0%)
**
**
**
**
**
Drug abuse or dependence; n (%)
6 (0.0%)
7 (0.0%)
2 (0.0%)
2 (0.0%)
**
**
**
**
**
COPD; n (%)
983 (5.0%)
998 (5.1%)
693 (3.0%)
666 (2.9%)
2,671 (8.0%)
2,602 (7.8%)
4,347 (5.7%)
4,266 (5.6%)
0.00
Table 1

Asthma; n (%)
870 (4.5%)
847 (4.3%)
804 (3.5%)
802 (3.5%)
1,756 (5.3%)
1,728 (5.2%)
3,430 (4.5%)
3,377 (4.4%)
0.00
Obstructive sleep apnea; n (%)
2,176 (11.1%)
2,157 (11.0%)
2,591 (11.2%)
2,584 (11.2%)
3,034 (9.1%)
3,034 (9.1%)
7,801 (10.3%)
7,775 (10.2%)
0.00
Pneumonia; n (%)
208 (1.1%)
221 (1.1%)
205 (0.9%)
210 (0.9%)
511 (1.5%)
520 (1.6%)
924 (1.2%)
951 (1.2%)
0.00
Imaging; n (%)
2 (0.0%)
6 (0.0%)
1 (0.0%)
2 (0.0%)
**
**
**
**
**
Diabetes Medications
DM Medications - AGIs; n (%)
112 (0.6%)
103 (0.5%)
91 (0.4%)
77 (0.3%)
231 (0.7%)
261 (0.8%)
434 (0.6%)
441 (0.6%)
0.00
DM Medications - Glitazones; n (%)
1,856 (9.5%)
1,876 (9.6%)
2,142 (9.2%)
2,148 (9.3%)
3,295 (9.9%)
3,279 (9.8%)
7,293 (9.6%)
7,303 (9.6%)
0.00
DM Medications - Insulin; n (%)
4,810 (24.6%)
4,865 (24.9%)
5,930 (25.6%)
5,958 (25.7%)
10,126 (30.3%)
10,087 (30.2%)
20,866 (27.4%)
20,910 (27.5%)
0.00
DM Medications - Meglitinides; n (%)
203 (1.0%)
194 (1.0%)
294 (1.3%)
272 (1.2%)
583 (1.7%)
542 (1.6%)
1,080 (1.4%)
1,008 (1.3%)
0.01
DM Medications - Metformin; n (%)
15,366 (78.7%)
15,269 (78.2%)
18,243 (78.7%)
18,260 (78.8%)
24,894 (74.5%)
24,848 (74.4%)
58,503 (76.9%)
58,377 (76.7%)
0.00
Concomitant initiation or current use of 2nd 
Generation SUs; n (%)
6,481 (33.2%)
6,440 (33.0%)
7,299 (31.5%)
7,328 (31.6%)
12,787 (38.3%)
12,548 (37.6%)
26,567 (34.9%)
26,316 (34.6%)
0.01
Concomitant initiation or current use of AGIs; n (%)
50 (0.3%)
77 (0.4%)
33 (0.1%)
50 (0.2%)
154 (0.5%)
175 (0.5%)
237 (0.3%)
302 (0.4%)
-0.02
Concomitant initiation or current use of Glitazones; 
n (%)
1,422 (7.3%)
1,425 (7.3%)
1,643 (7.1%)
1,624 (7.0%)
2,474 (7.4%)
2,510 (7.5%)
5,539 (7.3%)
5,559 (7.3%)
0.00
Concomitant initiation or current use of GLP-1 RA; n 
(%)
1,432 (7.3%)
1,544 (7.9%)
1,891 (8.2%)
1,968 (8.5%)
2,410 (7.2%)
2,543 (7.6%)
5,733 (7.5%)
6,055 (8.0%)
-0.02
Concomitant initiation or current use of Insulin; n 
(%)
3,600 (18.4%)
3,644 (18.7%)
4,552 (19.6%)
4,589 (19.8%)
7,923 (23.7%)
7,913 (23.7%)
16,075 (21.1%)
16,146 (21.2%)
0.00
Concomitant initiation or current use of 
Meglitinides; n (%)
110 (0.6%)
131 (0.7%)
108 (0.5%)
199 (0.9%)
404 (1.2%)
381 (1.1%)
622 (0.8%)
711 (0.9%)
-0.01
Concomitant initiation or current use of Metformin; 
n (%)
13,063 (66.9%)
12,913 (66.1%)
15,539 (67.1%)
15,521 (67.0%)
21,246 (63.6%)
21,219 (63.5%)
49,848 (65.5%)
49,653 (65.2%)
0.01
Past use of 2nd Generation SUs ; n (%)
1,625 (8.3%)
1,648 (8.4%)
1,695 (7.3%)
1,732 (7.5%)
2,612 (7.8%)
2,636 (7.9%)
5,932 (7.8%)
6,016 (7.9%)
0.00
Past use of AGIs ; n (%)
62 (0.3%)
26 (0.1%)
58 (0.3%)
27 (0.1%)
77 (0.2%)
86 (0.3%)
197 (0.3%)
139 (0.2%)
0.02
Past use of Glitazones ; n (%)
434 (2.2%)
451 (2.3%)
499 (2.2%)
524 (2.3%)
821 (2.5%)
769 (2.3%)
1,754 (2.3%)
1,744 (2.3%)
0.00
Past use of GLP-1 RA ; n (%)
926 (4.7%)
958 (4.9%)
1,232 (5.3%)
1,223 (5.3%)
1,589 (4.8%)
1,615 (4.8%)
3,747 (4.9%)
3,796 (5.0%)
0.00
Past use of Insulin ; n (%)
1,210 (6.2%)
1,221 (6.3%)
1,379 (6.0%)
1,369 (5.9%)
2,204 (6.6%)
2,175 (6.5%)
4,793 (6.3%)
4,765 (6.3%)
0.00
Past use of Meglitinides ; n (%)
93 (0.5%)
63 (0.3%)
186 (0.8%)
73 (0.3%)
179 (0.5%)
161 (0.5%)
458 (0.6%)
297 (0.4%)
0.03
Past use of metformin (final) ; n (%)
2,303 (11.8%)
2,356 (12.1%)
2,705 (11.7%)
2,739 (11.8%)
3,648 (10.9%)
3,629 (10.9%)
8,656 (11.4%)
8,724 (11.5%)
0.00
Other Medications
Use of ACE inhibitors; n (%)
10,585 (54.2%)
10,617 (54.4%)
12,359 (53.3%)
12,301 (53.1%)
16,705 (50.0%)
16,765 (50.2%)
39,649 (52.1%)
39,683 (52.1%)
0.00
Use of ARBs; n (%)
7,026 (36.0%)
7,007 (35.9%)
8,593 (37.1%)
8,662 (37.4%)
12,369 (37.0%)
12,384 (37.1%)
27,988 (36.8%)
28,053 (36.9%)
0.00
Use of Loop Diuretics ; n (%)
1,811 (9.3%)
1,788 (9.2%)
1,879 (8.1%)
1,836 (7.9%)
5,110 (15.3%)
5,163 (15.5%)
8,800 (11.6%)
8,787 (11.5%)
0.00
Use of other diuretics; n (%)
505 (2.6%)
487 (2.5%)
581 (2.5%)
573 (2.5%)
1,151 (3.4%)
1,124 (3.4%)
2,237 (2.9%)
2,184 (2.9%)
0.00
Use of nitrates-United; n (%)
696 (3.6%)
705 (3.6%)
742 (3.2%)
742 (3.2%)
2,191 (6.6%)
2,134 (6.4%)
3,629 (4.8%)
3,581 (4.7%)
0.00
Use of other hypertension drugs; n (%)
1,040 (5.3%)
1,072 (5.5%)
1,133 (4.9%)
1,140 (4.9%)
2,470 (7.4%)
2,473 (7.4%)
4,643 (6.1%)
4,685 (6.2%)
0.00
Use of digoxin; n (%)
234 (1.2%)
218 (1.1%)
189 (0.8%)
217 (0.9%)
754 (2.3%)
737 (2.2%)
1,177 (1.5%)
1,172 (1.5%)
0.00
Use of Anti-arrhythmics; n (%)
153 (0.8%)
160 (0.8%)
165 (0.7%)
169 (0.7%)
504 (1.5%)
478 (1.4%)
822 (1.1%)
807 (1.1%)
0.00
Use of COPD/asthma meds; n (%)
2,610 (13.4%)
2,552 (13.1%)
3,182 (13.7%)
3,201 (13.8%)
5,500 (16.5%)
5,455 (16.3%)
11,292 (14.8%)
11,208 (14.7%)
0.00
Use of statins; n (%)
14,115 (72.3%)
14,168 (72.5%)
15,879 (68.5%)
16,013 (69.1%)
25,077 (75.1%)
25,241 (75.6%)
55,071 (72.4%)
55,422 (72.8%)
-0.01
Use of other lipid-lowering drugs; n (%)
2,443 (12.5%)
2,510 (12.9%)
3,546 (15.3%)
3,536 (15.3%)
5,010 (15.0%)
4,896 (14.7%)
10,999 (14.5%)
10,942 (14.4%)
0.00
Use of antiplatelet agents; n (%)
1,985 (10.2%)
1,937 (9.9%)
2,289 (9.9%)
2,327 (10.0%)
4,642 (13.9%)
4,642 (13.9%)
8,916 (11.7%)
8,906 (11.7%)
0.00
Use of oral anticoagulants (Dabigatran, Rivaroxaban, 
Apixaban, Warfarin); n (%)
833 (4.3%)
855 (4.4%)
799 (3.4%)
791 (3.4%)
2,604 (7.8%)
2,590 (7.8%)
4,236 (5.6%)
4,236 (5.6%)
0.00
Use of heparin and other low-molecular weight 
heparins; n (%)
18 (0.1%)
19 (0.1%)
0 (0.0%)
0 (0.0%)
61 (0.2%)
62 (0.2%)
079 (0.1%)
081 (0.1%)
0.00
Use of NSAIDs; n (%)
3,256 (16.7%)
3,211 (16.4%)
3,774 (16.3%)
3,788 (16.4%)
5,117 (15.3%)
5,126 (15.3%)
12,147 (16.0%)
12,125 (15.9%)
0.00
Use of oral corticosteroids; n (%)
2,279 (11.7%)
2,243 (11.5%)
2,550 (11.0%)
2,583 (11.1%)
4,680 (14.0%)
4,595 (13.8%)
9,509 (12.5%)
9,421 (12.4%)
0.00
Use of bisphosphonate (United); n (%)
232 (1.2%)
237 (1.2%)
149 (0.6%)
145 (0.6%)
715 (2.1%)
761 (2.3%)
1,096 (1.4%)
1,143 (1.5%)
-0.01
Use of opioids; n (%)
3,797 (19.4%)
3,784 (19.4%)
4,612 (19.9%)
4,603 (19.9%)
6,800 (20.4%)
6,685 (20.0%)
15,209 (20.0%)
15,072 (19.8%)
0.01
Use of antidepressants; n (%)
4,446 (22.8%)
4,408 (22.6%)
5,009 (21.6%)
4,990 (21.5%)
8,171 (24.5%)
8,112 (24.3%)
17,626 (23.2%)
17,510 (23.0%)
0.00
Use of antipsychotics; n (%)
347 (1.8%)
337 (1.7%)
272 (1.2%)
250 (1.1%)
668 (2.0%)
682 (2.0%)
1,287 (1.7%)
1,269 (1.7%)
0.00
Use of anticonvulsants; n (%)
2,716 (13.9%)
2,697 (13.8%)
2,509 (10.8%)
2,513 (10.8%)
5,149 (15.4%)
5,060 (15.1%)
10,374 (13.6%)
10,270 (13.5%)
0.00
Use of lithium; n (%)
29 (0.1%)
18 (0.1%)
27 (0.1%)
14 (0.1%)
48 (0.1%)
29 (0.1%)
104 (0.1%)
061 (0.1%)
0.00
Use of Benzos; n (%)
1,741 (8.9%)
1,703 (8.7%)
1,946 (8.4%)
1,965 (8.5%)
3,284 (9.8%)
3,237 (9.7%)
6,971 (9.2%)
6,905 (9.1%)
0.00
Use of anxiolytics/hypnotics; n (%)
1,016 (5.2%)
1,001 (5.1%)
1,247 (5.4%)
1,234 (5.3%)
1,747 (5.2%)
1,718 (5.1%)
4,010 (5.3%)
3,953 (5.2%)
0.00
Use of dementia meds; n (%)
126 (0.6%)
129 (0.7%)
79 (0.3%)
80 (0.3%)
747 (2.2%)
705 (2.1%)
952 (1.3%)
914 (1.2%)
0.01
Use of antiparkinsonian meds; n (%)
356 (1.8%)
357 (1.8%)
392 (1.7%)
365 (1.6%)
926 (2.8%)
944 (2.8%)
1,674 (2.2%)
1,666 (2.2%)
0.00
Any use of pramlintide; n (%)
3 (0.0%)
24 (0.1%)
6 (0.0%)
43 (0.2%)
**
**
**
**
**
Any use of 1st generation sulfonylureas; n (%)
0 (0.0%)
0 (0.0%)
1 (0.0%)
0 (0.0%)
**
**
**
**
**
Entresto (sacubitril/valsartan); n (%)
24 (0.1%)
14 (0.1%)
3 (0.0%)
4 (0.0%)
14 (0.0%)
13 (0.0%)
041 (0.1%)
031 (0.0%)
0.00
Initiation as monotherapy  ; n (%)
1,207 (6.2%)
1,196 (6.1%)
1,314 (5.7%)
1,306 (5.6%)
1,176 (3.5%)
1,217 (3.6%)
3,697 (4.9%)
3,719 (4.9%)
0.00
Labs
                                          42,700                                           42,700 
Lab values- HbA1c (%) ; n (%)
8,392 (43.0%)
8,484 (43.4%)
1,674 (7.2%)
1,435 (6.2%)
N/A
N/A
10,066 (23.6%)
9,919 (23.2%)
0.01
Lab values- HbA1c (%) (within 3 months) ; n (%)
6,836 (35.0%)
6,971 (35.7%)
1,370 (5.9%)
1,224 (5.3%)
N/A
N/A
8,206 (19.2%)
8,195 (19.2%)
0.00
Lab values- HbA1c (%) (within 6 months) ; n (%)
8,392 (43.0%)
8,484 (43.4%)
1,674 (7.2%)
1,435 (6.2%)
N/A
N/A
10,066 (23.6%)
9,919 (23.2%)
0.01
Table 1

Lab values- BNP; n (%)
102 (0.5%)
120 (0.6%)
23 (0.1%)
4 (0.0%)
N/A
N/A
125 (0.3%)
124 (0.3%)
0.00
Lab values- BNP (within 3 months); n (%)
62 (0.3%)
76 (0.4%)
18 (0.1%)
3 (0.0%)
N/A
N/A
080 (0.2%)
079 (0.2%)
0.00
Lab values- BNP (within 6 months); n (%)
102 (0.5%)
120 (0.6%)
23 (0.1%)
4 (0.0%)
N/A
N/A
125 (0.3%)
124 (0.3%)
0.00
Lab values- BUN (mg/dl); n (%)
8,334 (42.7%)
8,259 (42.3%)
1,582 (6.8%)
1,359 (5.9%)
N/A
N/A
9,916 (23.2%)
9,618 (22.5%)
0.02
Lab values- BUN (mg/dl) (within 3 months); n (%)
6,579 (33.7%)
6,626 (33.9%)
1,244 (5.4%)
1,116 (4.8%)
N/A
N/A
7,823 (18.3%)
7,742 (18.1%)
0.01
Lab values- BUN (mg/dl) (within 6 months); n (%)
8,334 (42.7%)
8,259 (42.3%)
1,582 (6.8%)
1,359 (5.9%)
N/A
N/A
9,916 (23.2%)
9,618 (22.5%)
0.02
Lab values- Creatinine (mg/dl) ; n (%)
8,573 (43.9%)
8,526 (43.7%)
1,691 (7.3%)
1,486 (6.4%)
N/A
N/A
10,264 (24.0%)
10,012 (23.4%)
0.01
Lab values- Creatinine (mg/dl) (within 3 months) ; n 
(%)
6,780 (34.7%)
6,835 (35.0%)
1,337 (5.8%)
1,232 (5.3%)
N/A
N/A
8,117 (19.0%)
8,067 (18.9%)
0.00
Lab values- Creatinine (mg/dl) (within 6 months) ; n 
(%)
8,573 (43.9%)
8,526 (43.7%)
1,691 (7.3%)
1,486 (6.4%)
N/A
N/A
10,264 (24.0%)
10,012 (23.4%)
0.01
Lab values- HDL level (mg/dl); n (%)
7,438 (38.1%)
7,329 (37.5%)
1,535 (6.6%)
1,315 (5.7%)
N/A
N/A
8,973 (21.0%)
8,644 (20.2%)
0.02
Lab values- HDL level (mg/dl) (within 3 months); n (%)
5,579 (28.6%)
5,616 (28.8%)
1,181 (5.1%)
1,045 (4.5%)
N/A
N/A
6,760 (15.8%)
6,661 (15.6%)
0.01
Lab values- HDL level (mg/dl) (within 6 months); n (%)
7,438 (38.1%)
7,329 (37.5%)
1,535 (6.6%)
1,315 (5.7%)
N/A
N/A
8,973 (21.0%)
8,644 (20.2%)
0.02
Lab values- LDL level (mg/dl) ; n (%)
7,633 (39.1%)
7,557 (38.7%)
1,599 (6.9%)
1,341 (5.8%)
N/A
N/A
9,232 (21.6%)
8,898 (20.8%)
0.02
Lab values- LDL level (mg/dl) (within 3 months) ; n (%)
5,723 (29.3%)
5,809 (29.7%)
1,227 (5.3%)
1,068 (4.6%)
N/A
N/A
6,950 (16.3%)
6,877 (16.1%)
0.01
Lab values- LDL level (mg/dl) (within 6 months) ; n (%)
7,633 (39.1%)
7,557 (38.7%)
1,599 (6.9%)
1,341 (5.8%)
N/A
N/A
9,232 (21.6%)
8,898 (20.8%)
0.02
Lab values- NT-proBNP; n (%)
14 (0.1%)
12 (0.1%)
3 (0.0%)
0 (0.0%)
N/A
N/A
17 (0.0%)
0 (0.0%)
-
Lab values- NT-proBNP (within 3 months); n (%)
9 (0.0%)
7 (0.0%)
3 (0.0%)
0 (0.0%)
N/A
N/A
12 (0.0%)
0 (0.0%)
-
Lab values- NT-proBNP (within 6 months); n (%)
14 (0.1%)
12 (0.1%)
3 (0.0%)
0 (0.0%)
N/A
N/A
17 (0.0%)
12 (0.0%)
-
Lab values- Total cholesterol (mg/dl) ; n (%)
7,546 (38.6%)
7,484 (38.3%)
1,541 (6.7%)
1,326 (5.7%)
N/A
N/A
9,087 (21.3%)
8,810 (20.6%)
0.02
Lab values- Total cholesterol (mg/dl) (within 3 
months) ; n (%)
5,669 (29.0%)
5,759 (29.5%)
1,188 (5.1%)
1,059 (4.6%)
N/A
N/A
6,857 (16.1%)
6,818 (16.0%)
0.00
Lab values- Total cholesterol (mg/dl) (within 6 
months) ; n (%)
7,546 (38.6%)
7,484 (38.3%)
1,541 (6.7%)
1,326 (5.7%)
N/A
N/A
9,087 (21.3%)
8,810 (20.6%)
0.02
Lab values- Triglyceride level (mg/dl); n (%)
7,490 (38.3%)
7,438 (38.1%)
1,519 (6.6%)
1,304 (5.6%)
N/A
N/A
9,009 (21.1%)
8,742 (20.5%)
0.01
Lab values- Triglyceride level (mg/dl) (within 3 
months); n (%)
5,623 (28.8%)
5,720 (29.3%)
1,169 (5.0%)
1,046 (4.5%)
N/A
N/A
6,792 (15.9%)
6,766 (15.8%)
0.00
Lab values- Triglyceride level (mg/dl) (within 6 
months); n (%)
7,490 (38.3%)
7,438 (38.1%)
1,519 (6.6%)
1,304 (5.6%)
N/A
N/A
9,009 (21.1%)
8,742 (20.5%)
0.01
Lab result number- HbA1c (%) mean (only 2 to 20 
included) 
8,349
                                            
8,430
                                            
1,628
                                            
1,384
                                            
N/A
N/A                                              9,977                                              9,814 
...mean (sd)
8.53 (1.83)
8.61 (1.75)
8.63 (1.88)
8.63 (1.72)
N/A
N/A
8.55 (1.84)
8.61 (1.75)
-0.03
...median [IQR]
8.10 [7.30, 9.45]
8.30 [7.40, 9.60]
8.20 [7.30, 9.50]
8.30 [7.40, 9.59]
N/A
N/A
8.12 (1.84)
8.30 (1.75)
-0.10
...Missing; n (%)
11,183 (57.3%)
11,102 (56.8%)
21,540 (93.0%)
21,784 (94.0%)
N/A
N/A
32,723 (76.6%)
32,886 (77.0%)
-0.01
Lab result number- BNP mean 
102
                                                
120
                                                
23
                                                   
4
                                                      
N/A
N/A                                                  125                                                  124 
...mean (sd)
119.72 (204.33)
95.52 (162.94)
239.13 (519.14)
335.38 (447.47)
N/A
N/A
141.69 (288.38)
103.26 (176.28)
0.16
...median [IQR]
48.55 [20.27, 141.98]
44.35 [21.32, 88.78]
49.00 [20.00, 214.00]
192.50 [4.25, 809.38]
N/A
N/A
#VALUE!
49.13 (176.28)
#VALUE!
...Missing; n (%)
19,430 (99.5%)
19,412 (99.4%)
23,145 (99.9%)
23,164 (100.0%)
N/A
N/A
42,575 (99.7%)
42,576 (99.7%)
0.00
Lab result number- BUN (mg/dl) mean 
                                             8,334                                              8,259                                              1,582                                              1,359 
N/A
N/A                                              9,916                                              9,618 
...mean (sd)
17.03 (6.43)
16.93 (5.80)
629.58 (9,120.88)
3,069.88 (21,521.68)
N/A
N/A
114.76 (3642.51)
448.30 (8088.19)
-0.05
...median [IQR]
16.00 [13.00, 20.00]
16.00 [13.00, 19.50]
15.50 [12.50, 19.00]
16.00 [13.00, 20.00]
N/A
N/A
#VALUE!
#VALUE!
#VALUE!
...Missing; n (%)
11,198 (57.3%)
11,273 (57.7%)
21,586 (93.2%)
21,809 (94.1%)
N/A
N/A
32,784 (76.8%)
33,082 (77.5%)
-0.02
Lab result number- Creatinine (mg/dl) mean (only 0.1 
to 15 included) 
                                             8,519                                              8,459                                              1,536                                              1,339 
N/A
N/A                                           10,055                                              9,798 
...mean (sd)
0.96 (0.31)
0.92 (0.24)
0.96 (0.30)
0.93 (0.23)
N/A
N/A
0.96 (0.31)
0.92 (0.24)
0.14
...median [IQR]
0.90 [0.77, 1.09]
0.89 [0.75, 1.04]
0.92 [0.77, 1.07]
0.90 [0.77, 1.06]
N/A
N/A
0.90 (0.31)
0.89 (0.24)
0.04
...Missing; n (%)
11,013 (56.4%)
11,073 (56.7%)
21,632 (93.4%)
21,829 (94.2%)
N/A
N/A
32,645 (76.5%)
32,902 (77.1%)
-0.01
Lab result number- HDL level (mg/dl) mean (only 
=<5000 included) 
                                             7,438                                              7,329                                              1,528                                              1,294 
N/A
N/A                                              8,966                                              8,623 
...mean (sd)
44.89 (13.09)
44.78 (12.83)
43.55 (14.91)
43.02 (13.62)
N/A
N/A
44.66 (13.42)
44.52 (12.95)
0.01
...median [IQR]
43.00 [36.00, 51.50]
43.00 [36.00, 52.00]
42.83 [35.00, 51.00]
42.00 [35.00, 50.00]
N/A
N/A
42.97 (13.42)
42.85 (12.95)
0.01
...Missing; n (%)
12,094 (61.9%)
12,203 (62.5%)
21,640 (93.4%)
21,874 (94.4%)
N/A
N/A
33,734 (79.0%)
34,077 (79.8%)
-0.02
Lab result number- LDL level (mg/dl) mean (only 
=<5000 included) 
                                             7,492                                              7,432                                              1,416                                              1,187 
N/A
N/A                                              8,908                                              8,619 
...mean (sd)
85.61 (39.60)
84.29 (39.26)
87.73 (41.40)
87.33 (40.93)
N/A
N/A
85.95 (39.89)
84.71 (39.50)
0.03
...median [IQR]
83.00 [62.00, 109.00]
82.00 [61.00, 106.00]
87.00 [64.00, 113.00]
88.00 [63.00, 112.00]
N/A
N/A
83.64 (39.89)
82.83 (39.50)
0.02
...Missing; n (%)
12,040 (61.6%)
12,100 (61.9%)
21,752 (93.9%)
21,981 (94.9%)
N/A
N/A
33,792 (79.1%)
34,081 (79.8%)
-0.02
Lab result number- Total cholesterol (mg/dl) mean 
(only =<5000 included) 
                                             7,541                                              7,474                                              1,534                                              1,304 
N/A
N/A                                              9,075                                              8,778 
...mean (sd)
173.51 (47.47)
172.60 (46.68)
172.33 (52.31)
173.37 (48.27)
N/A
N/A
173.31 (48.32)
172.71 (46.92)
0.01
...median [IQR]
167.00 [142.00, 198.25]
167.00 [142.00, 196.00]
170.00 [143.38, 199.50]
171.00 [147.00, 198.00]
N/A
N/A
167.51 (48.32)
167.59 (46.92)
0.00
...Missing; n (%)
11,991 (61.4%)
12,058 (61.7%)
21,634 (93.4%)
21,864 (94.4%)
N/A
N/A
33,625 (78.7%)
33,922 (79.4%)
-0.02
Table 1

Lab result number- Triglyceride level (mg/dl) mean 
(only =<5000 included) 
                                             7,489                                              7,436                                              1,511                                              1,283 
N/A
N/A                                              9,000                                              8,719 
...mean (sd)
197.03 (176.04)
200.03 (177.75)
188.47 (180.91)
204.69 (194.45)
N/A
N/A
195.59 (176.88)
200.72 (180.31)
-0.03
...median [IQR]
158.00 [112.00, 228.00]
161.00 [114.00, 230.92]
150.50 [104.50, 223.33]
163.00 [113.00, 237.00]
N/A
N/A
156.74 (176.88)
161.29 (180.31)
-0.03
...Missing; n (%)
12,043 (61.7%)
12,096 (61.9%)
21,657 (93.5%)
21,885 (94.5%)
N/A
N/A
33,700 (78.9%)
33,981 (79.6%)
-0.02
Lab result number- Hemoglobin mean (only >0 
included)
                                             5,576                                              5,481                                              1,032                                                  879 
N/A
N/A                                              6,608                                              6,360 
...mean (sd)
13.80 (1.57)
14.00 (1.57)
20,324.36 (440,120.87)
3,301.14 (20,906.38)
N/A
N/A
3185.79 (173886.11)
468.31 (7769.62)
0.02
...median [IQR]
13.80 [12.71, 14.80]
14.00 [12.90, 15.08]
13.70 [12.70, 14.80]
14.00 [12.90, 15.00]
N/A
N/A
#VALUE!
#VALUE!
#VALUE!
...Missing; n (%)
13,956 (71.5%)
14,051 (71.9%)
22,136 (95.5%)
22,289 (96.2%)
N/A
N/A
36,092 (84.5%)
36,340 (85.1%)
-0.02
Lab result number- Serum sodium mean (only > 90 
and < 190 included)
                                             8,349                                              8,307                                              1,543                                              1,339 
N/A
N/A                                              9,892                                              9,646 
...mean (sd)
139.26 (2.68)
139.23 (2.69)
138.98 (2.54)
138.92 (2.39)
N/A
N/A
139.22 (2.66)
139.19 (2.65)
0.01
...median [IQR]
139.33 [138.00, 141.00]
139.00 [138.00, 141.00]
139.00 [137.33, 140.62]
139.00 [137.00, 140.33]
N/A
N/A
139.28 (2.66)
139.00 (2.65)
0.11
...Missing; n (%)
11,183 (57.3%)
11,225 (57.5%)
21,625 (93.3%)
21,829 (94.2%)
N/A
N/A
32,808 (76.8%)
33,054 (77.4%)
-0.01
Lab result number- Albumin mean (only >0 and <=10 
included)
                                             7,829                                              7,803                                              1,323                                              1,145 
N/A
N/A                                              9,152                                              8,948 
...mean (sd)
4.29 (0.31)
4.30 (0.30)
4.15 (0.71)
4.17 (0.66)
N/A
N/A
4.27 (0.39)
4.28 (0.37)
-0.03
...median [IQR]
4.30 [4.10, 4.50]
4.30 [4.10, 4.50]
4.25 [4.00, 4.45]
4.25 [4.00, 4.50]
N/A
N/A
4.29 (0.39)
4.29 (0.37)
0.00
...Missing; n (%)
11,703 (59.9%)
11,729 (60.1%)
21,845 (94.3%)
22,023 (95.1%)
N/A
N/A
33,548 (78.6%)
33,752 (79.0%)
-0.01
Lab result number- Glucose (fasting or random) mean 
(only 10-1000 included)
                                             8,366                                              8,303                                              1,537                                              1,326 
N/A
N/A                                              9,903                                              9,629 
...mean (sd)
180.41 (72.14)
181.43 (70.42)
181.84 (71.36)
182.28 (68.00)
N/A
N/A
180.63 (72.02)
181.55 (70.10)
-0.01
...median [IQR]
163.50 [130.00, 214.00]
166.50 [132.00, 216.00]
165.00 [132.33, 215.75]
168.25 [134.00, 217.12]
N/A
N/A
163.73 (72.02)
166.74 (70.10)
-0.04
...Missing; n (%)
11,166 (57.2%)
11,229 (57.5%)
21,631 (93.4%)
21,842 (94.3%)
N/A
N/A
32,797 (76.8%)
33,071 (77.4%)
-0.01
Lab result number- Potassium mean (only 1-7 
included)
                                             8,517                                              8,468                                              1,538                                              1,307 
N/A
N/A                                           10,055                                              9,775 
...mean (sd)
4.45 (0.42)
4.45 (0.41)
4.36 (0.44)
4.36 (0.44)
N/A
N/A
4.44 (0.42)
4.44 (0.41)
0.00
...median [IQR]
4.40 [4.20, 4.70]
4.40 [4.20, 4.70]
4.35 [4.00, 4.60]
4.40 [4.10, 4.60]
N/A
N/A
4.39 (0.42)
4.40 (0.41)
-0.02
...Missing; n (%)
11,015 (56.4%)
11,064 (56.6%)
21,630 (93.4%)
21,861 (94.4%)
N/A
N/A
32,645 (76.5%)
32,925 (77.1%)
-0.01
Comorbidity Scores
CCI (180 days)- ICD9 and ICD10 
...mean (sd)
2.09 (1.28)
2.10 (1.31)
1.67 (1.00)
1.67 (1.00)
2.36 (1.50)
2.35 (1.50)
2.08 (1.31)
2.08 (1.32)
0.00
...median [IQR]
2.00 [1.00, 2.00]
2.00 [1.00, 2.00]
1.00 [1.00, 2.00]
1.00 [1.00, 2.00]
2.00 [1.00, 3.00]
2.00 [1.00, 3.00]
1.70 (1.31)
1.70 (1.32)
0.00
Frailty Score: Qualitative Version 365 days as 
Categories, v1
...0; n (%)
13,009 (66.6%)
12,920 (66.1%)
12,672 (54.7%)
12,648 (54.6%)
15,535 (46.5%)
15,495 (46.4%)
41,216 (54.2%)
41,063 (54.0%)
0.00
...1 to 2; n (%)
5,078 (26.0%)
5,112 (26.2%)
8,472 (36.6%)
8,480 (36.6%)
11,515 (34.5%)
11,612 (34.8%)
25,065 (32.9%)
25,204 (33.1%)
0.00
...3 or more; n (%)
1,445 (7.4%)
1,500 (7.7%)
2,024 (8.7%)
2,040 (8.8%)
6,351 (19.0%)
6,294 (18.8%)
9,820 (12.9%)
9,834 (12.9%)
0.00
Frailty Score: Empirical Version 365 days as 
Categories, 
...< 0.12908; n (%)
6,873 (35.2%)
6,844 (35.0%)
7,705 (33.3%)
7,732 (33.4%)
5,501 (16.5%)
5,302 (15.9%)
20,079 (26.4%)
19,878 (26.1%)
0.01
...0.12908 - 0.1631167; n (%)
7,260 (37.2%)
7,324 (37.5%)
9,157 (39.5%)
9,149 (39.5%)
10,406 (31.2%)
10,542 (31.6%)
26,823 (35.2%)
27,015 (35.5%)
-0.01
...>= 0.1631167; n (%)
5,399 (27.6%)
5,364 (27.5%)
6,306 (27.2%)
6,287 (27.1%)
17,494 (52.4%)
17,557 (52.6%)
29,199 (38.4%)
29,208 (38.4%)
0.00
Non-Frailty; n (%)
11,171 (57.2%)
11,285 (57.8%)
12,238 (52.8%)
12,310 (53.1%)
1,723 (5.2%)
1,549 (4.6%)
25,132 (33.0%)
25,144 (33.0%)
0.00
Frailty Score (mean): Qualitative Version 365 days, v1
...mean (sd)
0.63 (1.18)
0.64 (1.18)
0.81 (1.19)
0.82 (1.20)
1.26 (1.67)
1.25 (1.64)
0.96 (1.42)
0.96 (1.41)
0.00
...median [IQR]
0.00 [0.00, 1.00]
0.00 [0.00, 1.00]
0.00 [0.00, 1.00]
0.00 [0.00, 1.00]
1.00 [0.00, 2.00]
1.00 [0.00, 2.00]
0.44 (1.42)
0.44 (1.41)
0.00
Frailty Score (mean): Empirical Version 365 days, 
...mean (sd)
0.15 (0.04)
0.15 (0.04)
0.14 (0.04)
0.14 (0.04)
0.18 (0.05)
0.18 (0.05)
0.16 (0.04)
0.16 (0.04)
0.00
...median [IQR]
0.14 [0.12, 0.17]
0.14 [0.12, 0.17]
0.14 [0.12, 0.16]
0.14 [0.12, 0.16]
0.17 [0.14, 0.20]
0.17 [0.14, 0.20]
0.15 (0.04)
0.15 (0.04)
0.00
Healthcare Utilization
Any hospitalization; n (%)
451 (2.3%)
488 (2.5%)
496 (2.1%)
517 (2.2%)
1,265 (3.8%)
1,237 (3.7%)
2,212 (2.9%)
2,242 (2.9%)
0.00
Any hospitalization within prior 30 days; n (%)
62 (0.3%)
83 (0.4%)
64 (0.3%)
79 (0.3%)
198 (0.6%)
207 (0.6%)
324 (0.4%)
369 (0.5%)
-0.01
Any hospitalization during prior 31-180 days; n (%)
394 (2.0%)
409 (2.1%)
436 (1.9%)
441 (1.9%)
1,094 (3.3%)
1,057 (3.2%)
1,924 (2.5%)
1,907 (2.5%)
0.00
Endocrinologist Visit; n (%)
2,773 (14.2%)
2,878 (14.7%)
3,445 (14.9%)
3,370 (14.5%)
5,826 (17.4%)
5,874 (17.6%)
12,044 (15.8%)
12,122 (15.9%)
0.00
Endocrinologist Visit (30 days prior); n (%)
1,974 (10.1%)
2,042 (10.5%)
2,569 (11.1%)
2,555 (11.0%)
4,001 (12.0%)
4,092 (12.3%)
8,544 (11.2%)
8,689 (11.4%)
-0.01
Endocrinologist Visit (31 to 180 days prior); n (%)
1,939 (9.9%)
1,992 (10.2%)
2,311 (10.0%)
2,302 (9.9%)
4,404 (13.2%)
4,479 (13.4%)
8,654 (11.4%)
8,773 (11.5%)
0.00
Internal medicine/family medicine visits; n (%)
14,481 (74.1%)
14,301 (73.2%)
20,561 (88.7%)
20,392 (88.0%)
27,892 (83.5%)
27,600 (82.6%)
62,934 (82.7%)
62,293 (81.9%)
0.02
Internal medicine/family medicine visits (30 days 
prior) ; n (%)
10,679 (54.7%)
10,582 (54.2%)
15,756 (68.0%)
15,756 (68.0%)
20,325 (60.9%)
20,166 (60.4%)
46,760 (61.4%)
46,504 (61.1%)
0.01
Internal medicine/family medicine visits (31 to 180 
days prior) ; n (%)
12,286 (62.9%)
12,278 (62.9%)
16,906 (73.0%)
16,939 (73.1%)
24,413 (73.1%)
24,255 (72.6%)
53,605 (70.4%)
53,472 (70.3%)
0.00
Cardiologist visit; n (%)
3,671 (18.8%)
3,733 (19.1%)
3,785 (16.3%)
3,767 (16.3%)
9,403 (28.2%)
9,408 (28.2%)
16,859 (22.2%)
16,908 (22.2%)
0.00
Number of Cardiologist visits (30 days prior); n (%)
1,085 (5.6%)
1,159 (5.9%)
1,191 (5.1%)
1,155 (5.0%)
2,831 (8.5%)
2,875 (8.6%)
5,107 (6.7%)
5,189 (6.8%)
0.00
Table 1

Number of Cardiologist visits (31 to 180 days prior); 
n (%)
3,120 (16.0%)
3,172 (16.2%)
3,152 (13.6%)
3,189 (13.8%)
8,218 (24.6%)
8,170 (24.5%)
14,490 (19.0%)
14,531 (19.1%)
0.00
Electrocardiogram ; n (%)
4,420 (22.6%)
4,428 (22.7%)
5,282 (22.8%)
5,287 (22.8%)
9,495 (28.4%)
9,314 (27.9%)
19,197 (25.2%)
19,029 (25.0%)
0.00
Use of glucose test strips; n (%)
684 (3.5%)
679 (3.5%)
913 (3.9%)
898 (3.9%)
981 (2.9%)
1,014 (3.0%)
2,578 (3.4%)
2,591 (3.4%)
0.00
Dialysis; n (%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
000 (0.0%)
000 (0.0%)
#DIV/0!
Naive new user v8 ; n (%)
1,875 (9.6%)
1,885 (9.7%)
1,971 (8.5%)
1,989 (8.6%)
1,878 (5.6%)
1,925 (5.8%)
5,724 (7.5%)
5,799 (7.6%)
0.00
N antidiabetic drugs at index date  
...mean (sd)
2.35 (0.86)
2.35 (0.88)
2.35 (0.87)
2.35 (0.90)
2.42 (0.86)
2.42 (0.87)
2.38 (0.86)
2.38 (0.88)
0.00
...median [IQR]
2.00 [2.00, 3.00]
2.00 [2.00, 3.00]
2.00 [2.00, 3.00]
2.00 [2.00, 3.00]
2.00 [2.00, 3.00]
2.00 [2.00, 3.00]
2.00 (0.86)
2.00 (0.88)
0.00
number of different/distinct medication 
prescriptions
...mean (sd)
9.98 (4.40)
9.99 (4.31)
9.72 (4.22)
9.71 (4.07)
10.35 (4.25)
10.32 (4.12)
10.06 (4.28)
10.05 (4.15)
0.00
...median [IQR]
9.00 [7.00, 12.00]
9.00 [7.00, 12.00]
9.00 [7.00, 12.00]
9.00 [7.00, 12.00]
10.00 [7.00, 13.00]
10.00 [7.00, 13.00]
9.44 (4.28)
9.44 (4.15)
0.00
Number of Hospitalizations
...mean (sd)
0.03 (0.17)
0.03 (0.18)
0.02 (0.16)
0.02 (0.16)
0.04 (0.23)
0.04 (0.23)
0.03 (0.20)
0.03 (0.20)
0.00
...median [IQR]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 (0.20)
0.00 (0.20)
0.00
Number of hospital days
...mean (sd)
0.11 (1.04)
0.12 (1.01)
0.10 (0.84)
0.11 (0.90)
0.22 (1.39)
0.22 (1.68)
0.16 (1.16)
0.16 (1.32)
0.00
...median [IQR]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 (1.16)
0.00 (1.32)
0.00
Number of Emergency Department (ED) visits 
...mean (sd)
0.21 (0.70)
0.21 (0.77)
0.05 (0.98)
0.05 (0.79)
0.30 (1.13)
0.30 (1.03)
0.20 (0.99)
0.20 (0.90)
0.00
...median [IQR]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 (0.99)
0.00 (0.90)
0.00
Number of Office visits
...mean (sd)
4.20 (3.19)
4.18 (3.01)
4.16 (3.17)
4.15 (3.01)
4.97 (3.57)
4.95 (3.49)
4.53 (3.36)
4.51 (3.23)
0.01
...median [IQR]
3.00 [2.00, 5.00]
3.00 [2.00, 5.00]
3.00 [2.00, 5.00]
3.00 [2.00, 5.00]
4.00 [2.00, 7.00]
4.00 [3.00, 6.00]
3.44 (3.36)
3.44 (3.23)
0.00
Number of Endocrinologist visits
...mean (sd)
0.69 (2.71)
0.74 (2.81)
0.71 (2.77)
0.75 (2.94)
1.01 (3.82)
1.13 (4.36)
0.84 (3.26)
0.91 (3.61)
-0.02
...median [IQR]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 (3.26)
0.00 (3.61)
0.00
Number of internal medicine/family medicine visits
...mean (sd)
7.21 (12.35)
7.16 (10.75)
6.39 (7.36)
6.54 (7.69)
7.45 (9.63)
7.60 (9.85)
7.07 (9.82)
7.16 (9.50)
-0.01
...median [IQR]
4.00 [0.00, 9.00]
4.00 [0.00, 9.00]
4.00 [2.00, 8.00]
4.00 [2.00, 9.00]
5.00 [2.00, 10.00]
5.00 [2.00, 10.00]
4.44 (9.82)
4.44 (9.50)
0.00
Number of Cardiologist visits
...mean (sd)
0.77 (2.66)
0.76 (2.51)
0.64 (2.39)
0.62 (2.14)
1.32 (3.64)
1.33 (3.67)
0.97 (3.06)
0.97 (2.99)
0.00
...median [IQR]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 1.00]
0.00 [0.00, 1.00]
0.00 (3.06)
0.00 (2.99)
0.00
Number electrocardiograms received 
...mean (sd)
0.35 (0.83)
0.35 (0.86)
0.34 (0.82)
0.34 (0.81)
0.49 (1.03)
0.48 (1.05)
0.41 (0.92)
0.40 (0.93)
0.01
...median [IQR]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 1.00]
0.00 [0.00, 1.00]
0.00 (0.92)
0.00 (0.93)
0.00
Number of HbA1c tests ordered
...mean (sd)
1.35 (0.88)
1.35 (0.86)
1.26 (0.88)
1.26 (0.86)
1.56 (0.86)
1.56 (0.80)
1.41 (0.87)
1.41 (0.83)
0.00
...median [IQR]
1.00 [1.00, 2.00]
1.00 [1.00, 2.00]
1.00 [1.00, 2.00]
1.00 [1.00, 2.00]
2.00 [1.00, 2.00]
2.00 [1.00, 2.00]
1.44 (0.87)
1.44 (0.83)
0.00
Number of glucose tests ordered
...mean (sd)
0.42 (1.48)
0.42 (1.17)
0.39 (0.99)
0.40 (1.12)
0.43 (1.03)
0.43 (1.07)
0.42 (1.15)
0.42 (1.11)
0.00
...median [IQR]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 (1.15)
0.00 (1.11)
0.00
Number of lipid tests ordered
...mean (sd)
1.05 (0.93)
1.05 (0.93)
1.04 (1.21)
1.04 (1.19)
1.11 (0.84)
1.10 (0.82)
1.07 (0.99)
1.07 (0.97)
0.00
...median [IQR]
1.00 [0.00, 2.00]
1.00 [0.00, 2.00]
1.00 [0.00, 1.00]
1.00 [0.00, 1.00]
1.00 [1.00, 2.00]
1.00 [1.00, 2.00]
1.00 (0.99)
1.00 (0.97)
0.00
Number of creatinine tests ordered
...mean (sd)
0.03 (0.22)
0.03 (0.22)
0.04 (0.24)
0.04 (0.24)
0.06 (0.32)
0.07 (0.33)
0.05 (0.27)
0.05 (0.28)
0.00
...median [IQR]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 (0.27)
0.00 (0.28)
0.00
Number of BUN tests ordered
...mean (sd)
0.02 (0.16)
0.02 (0.16)
0.02 (0.18)
0.02 (0.17)
0.04 (0.25)
0.04 (0.26)
0.03 (0.21)
0.03 (0.21)
0.00
...median [IQR]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 (0.21)
0.00 (0.21)
0.00
Number of tests for microalbuminuria
...mean (sd)
0.83 (1.17)
0.83 (1.15)
0.74 (1.09)
0.73 (1.09)
0.53 (0.72)
0.53 (0.72)
0.67 (0.97)
0.67 (0.96)
0.00
...median [IQR]
0.00 [0.00, 2.00]
0.00 [0.00, 2.00]
0.00 [0.00, 2.00]
0.00 [0.00, 2.00]
0.00 [0.00, 1.00]
0.00 [0.00, 1.00]
0.00 (0.97)
0.00 (0.96)
0.00
Total N distinct ICD9/ICD10 diagnoses at the 3rd 
digit level 
...mean (sd)
5.59 (5.88)
5.54 (5.90)
2.18 (3.30)
2.12 (3.35)
5.83 (6.80)
5.75 (6.82)
4.66 (5.70)
4.59 (5.72)
0.01
...median [IQR]
5.00 [0.00, 8.00]
5.00 [0.00, 8.00]
0.00 [0.00, 4.00]
0.00 [0.00, 4.00]
4.00 [0.00, 9.00]
4.00 [0.00, 9.00]
3.04 (5.70)
3.04 (5.72)
0.00
Use of thiazide; n (%)
2,545 (13.0%)
2,533 (13.0%) 2,933 (12.7%)
2,948 (12.7%) 5,006 (15.0%)
5,024 (15.0%) 10,484 (13.8%)
10,505 (13.8%)
0.00
Use of beta blockers; n (%)
7,182 (36.8%)
7,314 (37.4%) 8,219 (35.5%)
8,226 (35.5%) 16,252 (48.7%)
16,300 (48.8%) 31,653 (41.6%)
31,840 (41.8%)
0.00
Use of calcium channel blockers; n (%)
5,692 (29.1%)
5,762 (29.5%) 6,794 (29.3%)
6,841 (29.5%) 11,246 (33.7%)
11,422 (34.2%) 23,732 (31.2%)
24,025 (31.6%)
-0.01
Table 1

AFTER PS MATCHING
Optum
MarketScan
Medicare
BEFORE PS MATCHING
The c-statistics for the propensity score model, pre-matching was 0.795. The post-matching c-statistic 
was 0.524.
The c-statistics for the propensity score model, pre-matching was 0.786. The post-matching 
c-statistic was 0.52.
The c-statistics for the propensity score model, pre-matching was 0.805. The post-matching c-statistic 
was 0.525.
Appendix B: Canagliflozin vs 2nd Generation Sulfonylureas

Variable
Reference- 2nd 
Generation SUs
Exposure- Canagliflozin
Reference- 2nd 
Generation SUs
Exposure- Canagliflozin
Reference- 2nd 
Generation SUs
Exposure- 
Canagliflozin
Reference- 2nd 
Generation SUs
Exposure- Canagliflozin
St. Diff.
Number of patients
                                       154,886                                           17,154 
132,040
                                      
24,318
                                         
385,432
                                    
28,987
                       
                                       672,358                                           70,459 
Age
...mean (sd)
67.76 (9.26)
61.96 (7.84)
62.52 (9.22)
59.18 (6.40)
73.86 (7.06)
71.03 (5.27)
70.23 (8.06)
64.73 (6.37)
0.76
...median [IQR]
68.00 [61.00, 74.00]
61.00 [56.00, 67.00]
61.00 [56.00, 67.00]
59.00 [54.00, 63.00]
72.00 [68.00, 78.00]0.00 [67.00, 74.00]
68.92 (8.06)
64.01 (6.37)
0.68
Age categories 
...18 - 54; n (%)
14,732 (9.5%)
3,424 (20.0%)
25,558 (19.4%)
6,293 (25.9%)
0 (0.0%)
0 (0.0%)
40,290 (6.0%)
9,717 (13.8%)
-0.26
...55 - 64; n (%)
38,435 (24.8%)
7,427 (43.3%)
66,089 (50.1%)
14,196 (58.4%)
5,075 (1.3%)
329 (1.1%)
109,599 (16.3%)
21,952 (31.2%)
-0.36
...65 - 74; n (%)
65,092 (42.0%)
5,148 (30.0%)
24,049 (18.2%)
3,180 (13.1%)
227,622 (59.1%)
22,378 (77.2%)
316,763 (47.1%)
30,706 (43.6%)
0.07
...>= 75; n (%)
36,627 (23.6%)
1,155 (6.7%)
16,344 (12.4%)
649 (2.7%)
152,735 (39.6%)
6,280 (21.7%)
205,706 (30.6%)
8,084 (11.5%)
0.48
Gender 
...Males; n (%)
80,936 (52.3%)
9,575 (55.8%)
74,065 (56.1%)
13,608 (56.0%)
176,834 (45.9%)
14,378 (49.6%)
331,835 (49.4%)
37,561 (53.3%)
-0.08
...Females; n (%)
73,950 (47.7%)
7,579 (44.2%)
57,975 (43.9%)
10,710 (44.0%)
208,598 (54.1%)
14,609 (50.4%)
340,523 (50.6%)
32,898 (46.7%)
0.08
Race 
...White; n (%)
N/A
N/A
N/A
N/A
293,566 (76.2%)
23,286 (80.3%)
293,566 (76.2%)
23,286 (80.3%)
-0.10
...Black; n (%)
N/A
N/A
N/A
N/A
46,063 (12.0%)
2,353 (8.1%)
46,063 (12.0%)
2,353 (8.1%)
0.13
...Asian; n (%)
N/A
N/A
N/A
N/A
14,026 (3.6%)
1,041 (3.6%)
14,026 (3.6%)
1,041 (3.6%)
0.00
...Hispanic; n (%)
N/A
N/A
N/A
N/A
15,651 (4.1%)
982 (3.4%)
15,651 (4.1%)
982 (3.4%)
0.04
...North American Native; n (%)
N/A
N/A
N/A
N/A
2,642 (0.7%)
116 (0.4%)
2,642 (0.7%)
116 (0.4%)
0.04
...Other/Unknown; n (%)
N/A
N/A
N/A
N/A
13,484 (3.5%)
1,209 (4.2%)
13,484 (3.5%)
1,209 (4.2%)
-0.04
Region   (lumping missing&other category with West)
...Northeast; n (%)
16,655 (10.8%)
1,468 (8.6%)
21,643 (16.4%)
4,599 (18.9%)
63,475 (16.5%)
5,473 (18.9%)
101,773 (15.1%)
11,540 (16.4%)
-0.04
...South; n (%)
74,258 (47.9%)
9,215 (53.7%)
33,357 (25.3%)
4,231 (17.4%)
162,072 (42.0%)
12,619 (43.5%)
269,687 (40.1%)
26,065 (37.0%)
0.06
...Midwest; n (%)
31,842 (20.6%)
3,552 (20.7%)
57,680 (43.7%)
12,979 (53.4%)
95,692 (24.8%)
5,876 (20.3%)
185,214 (27.5%)
22,407 (31.8%)
-0.09
...West; n (%)
32,131 (20.7%)
2,919 (17.0%)
17,703 (13.4%)
2,224 (9.1%)
64,193 (16.7%)
5,019 (17.3%)
114,027 (17.0%)
10,162 (14.4%)
0.07
...Unknown+missing; n (%)
N/A
N/A
1,657 (1.3%)
285 (1.2%)
N/A
N/A
1,657 (1.3%)
285 (1.2%)
0.01
CV Covariates
Ischemic heart disease; n (%)
28,161 (18.2%)
2,488 (14.5%)
18,313 (13.9%)
2,973 (12.2%)
100,011 (25.9%)
7,262 (25.1%)
146,485 (21.8%)
12,723 (18.1%)
0.09
Acute MI; n (%)
644 (0.4%)
39 (0.2%)
444 (0.3%)
58 (0.2%)
1,926 (0.5%)
101 (0.3%)
3,014 (0.4%)
198 (0.3%)
0.02
ACS/unstable angina; n (%)
778 (0.5%)
76 (0.4%)
524 (0.4%)
81 (0.3%)
2,195 (0.6%)
149 (0.5%)
3,497 (0.5%)
306 (0.4%)
0.01
Old MI; n (%)
3,799 (2.5%)
290 (1.7%)
1,411 (1.1%)
196 (0.8%)
11,166 (2.9%)
703 (2.4%)
16,376 (2.4%)
1,189 (1.7%)
0.05
Stable angina; n (%)
4,163 (2.7%)
350 (2.0%)
2,056 (1.6%)
318 (1.3%)
10,964 (2.8%)
864 (3.0%)
17,183 (2.6%)
1,532 (2.2%)
0.03
Coronary atherosclerosis and other forms of chronic 
ischemic heart disease; n (%)
26,304 (17.0%)
2,355 (13.7%)
17,287 (13.1%)
2,811 (11.6%)
96,007 (24.9%)
6,954 (24.0%)
139,598 (20.8%)
12,120 (17.2%)
0.09
Other atherosclerosis with ICD10  Copy; n (%)
962 (0.6%)
74 (0.4%)
670 (0.5%)
132 (0.5%)
4,672 (1.2%)
340 (1.2%)
6,304 (0.9%)
546 (0.8%)
0.01
Previous cardiac procedure (CABG or PTCA or Stent) ; n (%)
256 (0.2%)
18 (0.1%)
227 (0.2%)
32 (0.1%)
734 (0.2%)
53 (0.2%)
1,217 (0.2%)
103 (0.1%)
0.03
History of CABG or PTCA; n (%)
6,458 (4.2%)
505 (2.9%)
2,302 (1.7%)
345 (1.4%)
24,925 (6.5%)
1,676 (5.8%)
33,685 (5.0%)
2,526 (3.6%)
0.07
Any stroke; n (%)
5,514 (3.6%)
452 (2.6%)
3,637 (2.8%)
480 (2.0%)
22,740 (5.9%)
1,588 (5.5%)
31,891 (4.7%)
2,520 (3.6%)
0.06
Ischemic stroke (w and w/o mention of cerebral 
infarction); n (%)
5,460 (3.5%)
449 (2.6%)
3,611 (2.7%)
475 (2.0%)
22,597 (5.9%)
1,580 (5.5%)
31,668 (4.7%)
2,504 (3.6%)
0.06
Hemorrhagic stroke; n (%)
72 (0.0%)
5 (0.0%)
44 (0.0%)
6 (0.0%)
231 (0.1%)
11 (0.0%)
347 (0.1%)
22 (0.0%)
0.04
TIA; n (%)
654 (0.4%)
52 (0.3%)
432 (0.3%)
47 (0.2%)
2,582 (0.7%)
152 (0.5%)
3,668 (0.5%)
251 (0.4%)
0.01
Other cerebrovascular disease; n (%)
1,586 (1.0%)
109 (0.6%)
842 (0.6%)
98 (0.4%)
6,208 (1.6%)
332 (1.1%)
8,636 (1.3%)
539 (0.8%)
0.05
Late effects of cerebrovascular disease; n (%)
1,489 (1.0%)
77 (0.4%)
610 (0.5%)
50 (0.2%)
5,373 (1.4%)
244 (0.8%)
7,472 (1.1%)
371 (0.5%)
0.07
Cerebrovascular procedure; n (%)
71 (0.0%)
5 (0.0%)
44 (0.0%)
4 (0.0%)
239 (0.1%)
17 (0.1%)
354 (0.1%)
26 (0.0%)
0.04
Heart failure (CHF); n (%)
10,952 (7.1%)
634 (3.7%)
5,273 (4.0%)
480 (2.0%)
36,922 (9.6%)
2,004 (6.9%)
53,147 (7.9%)
3,118 (4.4%)
0.15
Peripheral Vascular Disease (PVD) or PVD Surgery ; n (%)
9,275 (6.0%)
729 (4.2%)
4,752 (3.6%)
643 (2.6%)
34,887 (9.1%)
2,314 (8.0%)
48,914 (7.3%)
3,686 (5.2%)
0.09
Atrial fibrillation; n (%)
10,323 (6.7%)
740 (4.3%)
6,297 (4.8%)
765 (3.1%)
41,954 (10.9%)
2,419 (8.3%)
58,574 (8.7%)
3,924 (5.6%)
0.12
Other cardiac dysrhythmia; n (%)
12,809 (8.3%)
896 (5.2%)
6,775 (5.1%)
799 (3.3%)
43,918 (11.4%)
2,772 (9.6%)
63,502 (9.4%)
4,467 (6.3%)
0.12
Cardiac conduction disorders; n (%)
3,451 (2.2%)
225 (1.3%)
1,828 (1.4%)
211 (0.9%)
12,984 (3.4%)
758 (2.6%)
18,263 (2.7%)
1,194 (1.7%)
0.07
Other CVD; n (%)
13,518 (8.7%)
1,010 (5.9%)
8,464 (6.4%)
1,176 (4.8%)
48,376 (12.6%)
3,167 (10.9%)
70,358 (10.5%)
5,353 (7.6%)
0.10
Diabetes-related complications
Diabetic retinopathy; n (%)
8,707 (5.6%)
978 (5.7%)
4,265 (3.2%)
1,010 (4.2%)
22,583 (5.9%)
2,188 (7.5%)
35,555 (5.3%)
4,176 (5.9%)
-0.03
Diabetes with other ophthalmic manifestations; n (%)
1,194 (0.8%)
100 (0.6%)
2,603 (2.0%)
618 (2.5%)
8,498 (2.2%)
828 (2.9%)
12,295 (1.8%)
1,546 (2.2%)
-0.03
Retinal detachment, vitreous hemorrhage, vitrectomy; n 
(%)
541 (0.3%)
61 (0.4%)
305 (0.2%)
64 (0.3%)
1,186 (0.3%)
119 (0.4%)
2,032 (0.3%)
244 (0.3%)
0.00
Retinal laser coagulation therapy; n (%)
711 (0.5%)
104 (0.6%)
514 (0.4%)
115 (0.5%)
1,635 (0.4%)
205 (0.7%)
2,860 (0.4%)
424 (0.6%)
-0.03
Occurrence of Diabetic Neuropathy  Copy; n (%)
25,944 (16.8%)
2,962 (17.3%)
12,232 (9.3%)
2,705 (11.1%)
61,265 (15.9%)
5,766 (19.9%)
99,441 (14.8%)
11,433 (16.2%)
-0.04
Unmatched 
Optum
MarketScan
Medicare
POOLED
Table 1

Occurrence of diabetic nephropathy  with ICD10 Copy; n 
(%)
23,516 (15.2%)
1,648 (9.6%)
8,598 (6.5%)
1,283 (5.3%)
37,114 (9.6%)
2,340 (8.1%)
69,228 (10.3%)
5,271 (7.5%)
0.10
Hypoglycemia ; n (%)
2,683 (1.7%)
357 (2.1%)
2,848 (2.2%)
594 (2.4%)
7,156 (1.9%)
660 (2.3%)
12,687 (1.9%)
1,611 (2.3%)
-0.03
Hyperglycemia; n (%)
5,729 (3.7%)
582 (3.4%)
3,944 (3.0%)
627 (2.6%)
15,025 (3.9%)
1,020 (3.5%)
24,698 (3.7%)
2,229 (3.2%)
0.03
Disorders of fluid electrolyte and acid-base balance; n (%)
8,950 (5.8%)
552 (3.2%)
4,904 (3.7%)
534 (2.2%)
25,824 (6.7%)
1,227 (4.2%)
39,678 (5.9%)
2,313 (3.3%)
0.12
Diabetic ketoacidosis; n (%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
000 (0.0%)
00 (0.0%)
#DIV/0!
Hyperosmolar hyperglycemic nonketotic syndrome 
(HONK); n (%)
677 (0.4%)
76 (0.4%)
472 (0.4%)
73 (0.3%)
1,573 (0.4%)
144 (0.5%)
2,722 (0.4%)
293 (0.4%)
0.00
Diabetes with peripheral circulatory disorders with ICD-
10  Copy; n (%)
10,012 (6.5%)
787 (4.6%)
3,656 (2.8%)
613 (2.5%)
24,561 (6.4%)
1,804 (6.2%)
38,229 (5.7%)
3,204 (4.5%)
0.05
Diabetic Foot; n (%)
2,746 (1.8%)
225 (1.3%)
1,770 (1.3%)
267 (1.1%)
8,551 (2.2%)
561 (1.9%)
13,067 (1.9%)
1,053 (1.5%)
0.03
Gangrene ; n (%)
196 (0.1%)
21 (0.1%)
140 (0.1%)
5 (0.0%)
528 (0.1%)
19 (0.1%)
864 (0.1%)
45 (0.1%)
0.00
Lower extremity amputation; n (%)
771 (0.5%)
46 (0.3%)
205 (0.2%)
24 (0.1%)
1,708 (0.4%)
84 (0.3%)
2,684 (0.4%)
154 (0.2%)
0.04
Osteomyelitis; n (%)
575 (0.4%)
43 (0.3%)
368 (0.3%)
45 (0.2%)
1,347 (0.3%)
74 (0.3%)
2,290 (0.3%)
162 (0.2%)
0.02
Skin infections ; n (%)
7,163 (4.6%)
798 (4.7%)
5,853 (4.4%)
994 (4.1%)
21,559 (5.6%)
1,617 (5.6%)
34,575 (5.1%)
3,409 (4.8%)
0.01
Erectile dysfunction; n (%)
4,013 (2.6%)
591 (3.4%)
3,090 (2.3%)
691 (2.8%)
7,642 (2.0%)
868 (3.0%)
14,745 (2.2%)
2,150 (3.1%)
-0.06
Diabetes with unspecified complication; n (%)
7,328 (4.7%)
839 (4.9%)
4,931 (3.7%)
1,046 (4.3%)
16,772 (4.4%)
1,530 (5.3%)
29,031 (4.3%)
3,415 (4.8%)
-0.02
Diabetes mellitus without mention of complications; n 
(%)
131,414 (84.8%)
14,605 (85.1%)
120,351 (91.1%)
22,432 (92.2%)
355,860 (92.3%)
26,575 (91.7%)
607,625 (90.4%)
63,612 (90.3%)
0.00
Hypertension: 1 inpatient or 2 outpatient claims within 
365 days; n (%)
140,329 (90.6%)
15,738 (91.7%)
111,054 (84.1%)
21,293 (87.6%)
364,169 (94.5%)
27,766 (95.8%)
615,552 (91.6%)
64,797 (92.0%)
-0.01
Hyperlipidemia ; n (%)
111,115 (71.7%)
13,329 (77.7%)
89,589 (67.8%)
18,477 (76.0%)
293,228 (76.1%)
23,958 (82.7%)
493,932 (73.5%)
55,764 (79.1%)
-0.13
Edema; n (%)
8,922 (5.8%)
767 (4.5%)
4,785 (3.6%)
772 (3.2%)
31,716 (8.2%)
2,111 (7.3%)
45,423 (6.8%)
3,650 (5.2%)
0.07
Renal Dysfunction (non-diabetic) ; n (%)
31,030 (20.0%)
1,617 (9.4%)
13,265 (10.0%)
1,233 (5.1%)
75,670 (19.6%)
3,535 (12.2%)
119,965 (17.8%)
6,385 (9.1%)
0.26
Occurrence of acute renal disease ; n (%)
3,885 (2.5%)
136 (0.8%)
1,944 (1.5%)
95 (0.4%)
10,543 (2.7%)
322 (1.1%)
16,372 (2.4%)
553 (0.8%)
0.13
Occurrence of chronic renal insufficiency; n (%)
26,302 (17.0%)
1,333 (7.8%)
9,757 (7.4%)
892 (3.7%)
63,348 (16.4%)
2,891 (10.0%)
99,407 (14.8%)
5,116 (7.3%)
0.24
Chronic kidney disease ; n (%)
25,400 (16.4%)
1,244 (7.3%)
9,238 (7.0%)
765 (3.1%)
60,327 (15.7%)
2,654 (9.2%)
94,965 (14.1%)
4,663 (6.6%)
0.25
CKD Stage 3-4; n (%)
17,724 (11.4%)
638 (3.7%)
6,019 (4.6%)
375 (1.5%)
42,095 (10.9%)
1,536 (5.3%)
65,838 (9.8%)
2,549 (3.6%)
0.25
Occurrence of hypertensive nephropathy; n (%)
11,901 (7.7%)
539 (3.1%)
4,074 (3.1%)
305 (1.3%)
25,957 (6.7%)
1,009 (3.5%)
41,932 (6.2%)
1,853 (2.6%)
0.18
Occurrence of miscellaneous renal insufficiency ; n (%)
6,270 (4.0%)
315 (1.8%)
3,464 (2.6%)
373 (1.5%)
20,943 (5.4%)
1,032 (3.6%)
30,677 (4.6%)
1,720 (2.4%)
0.12
Glaucoma or cataracts ; n (%)
29,202 (18.9%)
2,865 (16.7%)
18,976 (14.4%)
3,293 (13.5%)
96,718 (25.1%)
7,893 (27.2%)
144,896 (21.6%)
14,051 (19.9%)
0.04
Cellulitis or abscess of toe; n (%)
1,798 (1.2%)
152 (0.9%)
980 (0.7%)
137 (0.6%)
4,579 (1.2%)
308 (1.1%)
7,357 (1.1%)
597 (0.8%)
0.03
Foot ulcer; n (%)
2,634 (1.7%)
213 (1.2%)
1,736 (1.3%)
264 (1.1%)
8,482 (2.2%)
558 (1.9%)
12,852 (1.9%)
1,035 (1.5%)
0.03
Bladder stones; n (%)
170 (0.1%)
13 (0.1%)
132 (0.1%)
16 (0.1%)
548 (0.1%)
37 (0.1%)
850 (0.1%)
66 (0.1%)
0.00
Kidney stones; n (%)
2,807 (1.8%)
261 (1.5%)
2,375 (1.8%)
433 (1.8%)
8,275 (2.1%)
659 (2.3%)
13,457 (2.0%)
1,353 (1.9%)
0.01
Urinary tract infections (UTIs); n (%)
11,361 (7.3%)
883 (5.1%)
6,545 (5.0%)
963 (4.0%)
41,611 (10.8%)
2,560 (8.8%)
59,517 (8.9%)
4,406 (6.3%)
0.10
Dipstick urinalysis; n (%)
49,794 (32.1%)
5,364 (31.3%)
37,552 (28.4%)
7,447 (30.6%)
135,533 (35.2%)
10,690 (36.9%)
222,879 (33.1%)
23,501 (33.4%)
-0.01
Non-dipstick urinalysis; n (%)
64,593 (41.7%)
7,874 (45.9%)
44,790 (33.9%)
10,311 (42.4%)
151,194 (39.2%)
13,426 (46.3%)
260,577 (38.8%)
31,611 (44.9%)
-0.12
Urine function test; n (%)
2,926 (1.9%)
230 (1.3%)
2,192 (1.7%)
317 (1.3%)
10,601 (2.8%)
809 (2.8%)
15,719 (2.3%)
1,356 (1.9%)
0.03
Cytology; n (%)
733 (0.5%)
74 (0.4%)
752 (0.6%)
124 (0.5%)
2,588 (0.7%)
202 (0.7%)
4,073 (0.6%)
400 (0.6%)
0.00
Cystoscopy; n (%)
1,397 (0.9%)
110 (0.6%)
1,137 (0.9%)
161 (0.7%)
4,335 (1.1%)
295 (1.0%)
6,869 (1.0%)
566 (0.8%)
0.02
Other Covariates
Liver disease; n (%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
#VALUE!
000 (0.0%)
#VALUE!
Osteoarthritis; n (%)
18,548 (12.0%)
1,772 (10.3%)
10,553 (8.0%)
1,694 (7.0%)
64,696 (16.8%)
4,889 (16.9%)
93,797 (14.0%)
8,355 (11.9%)
0.06
Other arthritis, arthropathies and musculoskeletal pain; n 
(%)
43,333 (28.0%)
4,698 (27.4%)
31,686 (24.0%)
5,758 (23.7%)
134,642 (34.9%)
10,271 (35.4%)
209,661 (31.2%)
20,727 (29.4%)
0.04
Dorsopathies; n (%)
27,300 (17.6%)
3,034 (17.7%)
19,269 (14.6%)
3,723 (15.3%)
80,976 (21.0%)
6,590 (22.7%)
127,545 (19.0%)
13,347 (18.9%)
0.00
Fractures; n (%)
3,317 (2.1%)
299 (1.7%)
2,317 (1.8%)
355 (1.5%)
11,160 (2.9%)
681 (2.3%)
16,794 (2.5%)
1,335 (1.9%)
0.04
Falls ; n (%)
4,393 (2.8%)
292 (1.7%)
1,273 (1.0%)
126 (0.5%)
13,534 (3.5%)
651 (2.2%)
19,200 (2.9%)
1,069 (1.5%)
0.10
Osteoporosis; n (%)
6,177 (4.0%)
446 (2.6%)
2,182 (1.7%)
323 (1.3%)
23,320 (6.1%)
1,802 (6.2%)
31,679 (4.7%)
2,571 (3.6%)
0.06
Hyperthyroidism; n (%)
881 (0.6%)
92 (0.5%)
541 (0.4%)
104 (0.4%)
2,984 (0.8%)
244 (0.8%)
4,406 (0.7%)
440 (0.6%)
0.01
Hypothyroidism ; n (%)
21,624 (14.0%)
2,517 (14.7%)
13,319 (10.1%)
2,893 (11.9%)
44,004 (11.4%)
3,638 (12.6%)
78,947 (11.7%)
9,048 (12.8%)
-0.03
Other disorders of thyroid gland ; n (%)
4,419 (2.9%)
666 (3.9%)
3,264 (2.5%)
897 (3.7%)
12,341 (3.2%)
1,310 (4.5%)
20,024 (3.0%)
2,873 (4.1%)
-0.06
Depression; n (%)
10,169 (6.6%)
1,264 (7.4%)
7,134 (5.4%)
1,503 (6.2%)
32,440 (8.4%)
2,562 (8.8%)
49,743 (7.4%)
5,329 (7.6%)
-0.01
Anxiety; n (%)
9,789 (6.3%)
1,176 (6.9%)
5,860 (4.4%)
1,146 (4.7%)
26,959 (7.0%)
2,045 (7.1%)
42,608 (6.3%)
4,367 (6.2%)
0.00
Sleep_Disorder; n (%)
7,808 (5.0%)
1,334 (7.8%)
9,758 (7.4%)
2,822 (11.6%)
24,586 (6.4%)
2,463 (8.5%)
42,152 (6.3%)
6,619 (9.4%)
-0.12
Dementia; n (%)
4,899 (3.2%)
163 (1.0%)
2,106 (1.6%)
124 (0.5%)
23,566 (6.1%)
942 (3.2%)
30,571 (4.5%)
1,229 (1.7%)
0.16
Delirium; n (%)
1,146 (0.7%)
47 (0.3%)
567 (0.4%)
36 (0.1%)
4,774 (1.2%)
187 (0.6%)
6,487 (1.0%)
270 (0.4%)
0.07
Psychosis; n (%)
1,233 (0.8%)
77 (0.4%)
619 (0.5%)
46 (0.2%)
5,761 (1.5%)
258 (0.9%)
7,613 (1.1%)
381 (0.5%)
0.07
Obesity; n (%)
29,896 (19.3%)
4,631 (27.0%)
18,364 (13.9%)
4,643 (19.1%)
48,909 (12.7%)
5,747 (19.8%)
97,169 (14.5%)
15,021 (21.3%)
-0.18
Overweight; n (%)
8,442 (5.5%)
854 (5.0%)
2,983 (2.3%)
553 (2.3%)
12,502 (3.2%)
1,070 (3.7%)
23,927 (3.6%)
2,477 (3.5%)
0.01
Smoking; n (%)
14,958 (9.7%)
1,412 (8.2%)
7,989 (6.1%)
1,213 (5.0%)
44,623 (11.6%)
3,182 (11.0%)
67,570 (10.0%)
5,807 (8.2%)
0.06
Alcohol abuse or dependence; n (%)
56 (0.0%)
0 (0.0%)
37 (0.0%)
6 (0.0%)
**
**
**
**
**
Drug abuse or dependence; n (%)
63 (0.0%)
7 (0.0%)
25 (0.0%)
4 (0.0%)
**
**
**
**
**
COPD; n (%)
11,438 (7.4%)
842 (4.9%)
5,445 (4.1%)
667 (2.7%)
35,836 (9.3%)
2,375 (8.2%)
52,719 (7.8%)
3,884 (5.5%)
0.09
Table 1

Asthma; n (%)
6,705 (4.3%)
826 (4.8%)
4,598 (3.5%)
883 (3.6%)
18,875 (4.9%)
1,554 (5.4%)
30,178 (4.5%)
3,263 (4.6%)
0.00
Obstructive sleep apnea; n (%)
12,320 (8.0%)
2,043 (11.9%)
11,112 (8.4%)
3,033 (12.5%)
23,357 (6.1%)
2,710 (9.3%)
46,789 (7.0%)
7,786 (11.1%)
-0.14
Pneumonia; n (%)
2,800 (1.8%)
193 (1.1%)
1,979 (1.5%)
213 (0.9%)
9,582 (2.5%)
478 (1.6%)
14,361 (2.1%)
884 (1.3%)
0.06
Imaging; n (%)
70 (0.0%)
3 (0.0%)
34 (0.0%)
3 (0.0%)
173 (0.0%)
12 (0.0%)
277 (0.0%)
18 (0.0%)
#DIV/0!
Diabetes Medications
DM Medications - AGIs; n (%)
589 (0.4%)
64 (0.4%)
395 (0.3%)
78 (0.3%)
1,594 (0.4%)
198 (0.7%)
2,578 (0.4%)
340 (0.5%)
-0.01
DM Medications - Glitazones; n (%)
10,422 (6.7%)
1,544 (9.0%)
8,718 (6.6%)
2,208 (9.1%)
24,517 (6.4%)
2,742 (9.5%)
43,657 (6.5%)
6,494 (9.2%)
-0.10
DM Medications - Insulin; n (%)
19,589 (12.6%)
5,087 (29.7%)
15,413 (11.7%)
7,310 (30.1%)
53,691 (13.9%)
10,058 (34.7%)
88,693 (13.2%)
22,455 (31.9%)
-0.46
DM Medications - Meglitinides; n (%)
924 (0.6%)
247 (1.4%)
1,054 (0.8%)
491 (2.0%)
3,952 (1.0%)
817 (2.8%)
5,930 (0.9%)
1,555 (2.2%)
-0.11
DM Medications - Metformin; n (%)
108,309 (69.9%)
13,385 (78.0%)
96,831 (73.3%)
19,082 (78.5%)
254,527 (66.0%)
21,505 (74.2%)
459,667 (68.4%)
53,972 (76.6%)
-0.18
Concomitant initiation or current use of DPP4i Copy; n 
(%)
17,486 (11.3%)
3,345 (19.5%)
21,174 (16.0%)
5,938 (24.4%)
51,735 (13.4%)
7,439 (25.7%)
90,395 (13.4%)
16,722 (23.7%)
-0.27
Concomitant initiation or current use of AGIs; n (%)
425 (0.3%)
45 (0.3%)
286 (0.2%)
39 (0.2%)
1,174 (0.3%)
139 (0.5%)
1,885 (0.3%)
223 (0.3%)
0.00
Concomitant initiation or current use of Glitazones; n (%)
8,576 (5.5%)
1,175 (6.8%)
7,176 (5.4%)
1,639 (6.7%)
20,067 (5.2%)
2,075 (7.2%)
35,819 (5.3%)
4,889 (6.9%)
-0.07
Concomitant initiation or current use of GLP-1 RA; n (%)
4,299 (2.8%)
2,107 (12.3%)
4,901 (3.7%)
3,223 (13.3%)
7,426 (1.9%)
2,835 (9.8%)
16,626 (2.5%)
8,165 (11.6%)
-0.36
Concomitant initiation or current use of Insulin; n (%)
13,776 (8.9%)
3,869 (22.6%)
11,356 (8.6%)
5,709 (23.5%)
39,091 (10.1%)
8,072 (27.8%)
64,223 (9.6%)
17,650 (25.1%)
-0.42
Concomitant initiation or current use of Meglitinides; n 
(%)
613 (0.4%)
171 (1.0%)
711 (0.5%)
321 (1.3%)
2,576 (0.7%)
581 (2.0%)
3,900 (0.6%)
1,073 (1.5%)
-0.09
Concomitant initiation or current use of Metformin; n (%)
92,596 (59.8%)
11,270 (65.7%)
83,076 (62.9%)
16,009 (65.8%)
217,493 (56.4%)
18,170 (62.7%)
393,165 (58.5%)
45,449 (64.5%)
-0.12
Past use of DPP4i Copy; n (%)
6,565 (4.2%)
1,159 (6.8%)
5,963 (4.5%)
1,809 (7.4%)
17,310 (4.5%)
2,138 (7.4%)
29,838 (4.4%)
5,106 (7.2%)
-0.12
Past use of AGIs Copy; n (%)
164 (0.1%)
19 (0.1%)
109 (0.1%)
39 (0.2%)
420 (0.1%)
59 (0.2%)
693 (0.1%)
117 (0.2%)
-0.03
Past use of Glitazones Copy; n (%)
1,846 (1.2%)
369 (2.2%)
1,543 (1.2%)
569 (2.3%)
4,450 (1.2%)
667 (2.3%)
7,839 (1.2%)
1,605 (2.3%)
-0.08
Past use of GLP-1 RA Copy; n (%)
2,375 (1.5%)
888 (5.2%)
2,076 (1.6%)
1,436 (5.9%)
4,256 (1.1%)
1,234 (4.3%)
8,707 (1.3%)
3,558 (5.0%)
-0.21
Past use of Insulin Copy; n (%)
5,813 (3.8%)
1,218 (7.1%)
4,057 (3.1%)
1,601 (6.6%)
14,604 (3.8%)
1,987 (6.9%)
24,474 (3.6%)
4,806 (6.8%)
-0.14
Past use of Meglitinides Copy; n (%)
311 (0.2%)
76 (0.4%)
343 (0.3%)
170 (0.7%)
1,376 (0.4%)
236 (0.8%)
2,030 (0.3%)
482 (0.7%)
-0.06
Past use of metformin (final) Copy; n (%)
15,713 (10.1%)
2,115 (12.3%)
13,756 (10.4%)
3,073 (12.6%)
37,034 (9.6%)
3,335 (11.5%)
66,503 (9.9%)
8,523 (12.1%)
-0.07
Other Medications
Use of ACE inhibitors; n (%)
84,706 (54.7%)
8,925 (52.0%)
72,224 (54.7%)
12,297 (50.6%)
197,008 (51.1%)
13,650 (47.1%)
353,938 (52.6%)
34,872 (49.5%)
0.06
Use of ARBs; n (%)
47,885 (30.9%)
6,552 (38.2%)
42,148 (31.9%)
9,717 (40.0%)
119,221 (30.9%)
11,500 (39.7%)
209,254 (31.1%)
27,769 (39.4%)
-0.17
Use of Loop Diuretics ; n (%)
19,348 (12.5%)
1,498 (8.7%)
12,373 (9.4%)
1,847 (7.6%)
68,480 (17.8%)
4,431 (15.3%)
100,201 (14.9%)
7,776 (11.0%)
0.12
Use of other diuretics; n (%)
4,344 (2.8%)
466 (2.7%)
3,400 (2.6%)
615 (2.5%)
13,410 (3.5%)
985 (3.4%)
21,154 (3.1%)
2,066 (2.9%)
0.01
Use of nitrates-United; n (%)
7,132 (4.6%)
547 (3.2%)
4,935 (3.7%)
735 (3.0%)
27,238 (7.1%)
1,788 (6.2%)
39,305 (5.8%)
3,070 (4.4%)
0.06
Use of other hypertension drugs; n (%)
11,822 (7.6%)
853 (5.0%)
8,348 (6.3%)
1,083 (4.5%)
34,116 (8.9%)
2,082 (7.2%)
54,286 (8.1%)
4,018 (5.7%)
0.09
Use of digoxin; n (%)
2,388 (1.5%)
178 (1.0%)
1,809 (1.4%)
225 (0.9%)
11,438 (3.0%)
609 (2.1%)
15,635 (2.3%)
1,012 (1.4%)
0.07
Use of Anti-arrhythmics; n (%)
1,811 (1.2%)
148 (0.9%)
1,428 (1.1%)
195 (0.8%)
7,241 (1.9%)
442 (1.5%)
10,480 (1.6%)
785 (1.1%)
0.04
Use of COPD/asthma meds; n (%)
18,661 (12.0%)
2,398 (14.0%)
16,481 (12.5%)
3,563 (14.7%)
54,930 (14.3%)
5,018 (17.3%)
90,072 (13.4%)
10,979 (15.6%)
-0.06
Use of statins; n (%)
106,155 (68.5%)
12,492 (72.8%)
85,402 (64.7%)
17,004 (69.9%)
267,482 (69.4%)
22,004 (75.9%)
459,039 (68.3%)
51,500 (73.1%)
-0.11
Use of other lipid-lowering drugs; n (%)
14,959 (9.7%)
2,353 (13.7%)
15,699 (11.9%)
3,931 (16.2%)
42,819 (11.1%)
4,445 (15.3%)
73,477 (10.9%)
10,729 (15.2%)
-0.13
Use of antiplatelet agents; n (%)
16,208 (10.5%)
1,683 (9.8%)
13,697 (10.4%)
2,526 (10.4%)
50,943 (13.2%)
4,302 (14.8%)
80,848 (12.0%)
8,511 (12.1%)
0.00
Use of oral anticoagulants (Dabigatran, Rivaroxaban, 
Apixaban, Warfarin); n (%)
9,071 (5.9%)
726 (4.2%)
6,372 (4.8%)
810 (3.3%)
35,017 (9.1%)
2,235 (7.7%)
50,460 (7.5%)
3,771 (5.4%)
0.09
Use of heparin and other low-molecular weight heparins; 
n (%)
309 (0.2%)
16 (0.1%)
7 (0.0%)
0 (0.0%)
1,042 (0.3%)
70 (0.2%)
1,358 (0.2%)
086 (0.1%)
0.03
Use of NSAIDs; n (%)
21,661 (14.0%)
2,844 (16.6%)
19,311 (14.6%)
3,992 (16.4%)
53,840 (14.0%)
4,711 (16.3%)
94,812 (14.1%)
11,547 (16.4%)
-0.06
Use of oral corticosteroids; n (%)
18,506 (11.9%)
2,069 (12.1%)
15,049 (11.4%)
2,725 (11.2%)
53,287 (13.8%)
4,148 (14.3%)
86,842 (12.9%)
8,942 (12.7%)
0.01
Use of bisphosphonate (United); n (%)
3,267 (2.1%)
202 (1.2%)
1,232 (0.9%)
166 (0.7%)
10,720 (2.8%)
820 (2.8%)
15,219 (2.3%)
1,188 (1.7%)
0.04
Use of opioids; n (%)
28,673 (18.5%)
3,296 (19.2%)
25,050 (19.0%)
4,773 (19.6%)
77,313 (20.1%)
5,898 (20.3%)
131,036 (19.5%)
13,967 (19.8%)
-0.01
Use of antidepressants; n (%)
30,934 (20.0%)
4,117 (24.0%)
24,343 (18.4%)
5,483 (22.5%)
84,498 (21.9%)
7,501 (25.9%)
139,775 (20.8%)
17,101 (24.3%)
-0.08
Use of antipsychotics; n (%)
2,865 (1.8%)
313 (1.8%)
1,708 (1.3%)
306 (1.3%)
10,029 (2.6%)
710 (2.4%)
14,602 (2.2%)
1,329 (1.9%)
0.02
Use of anticonvulsants; n (%)
20,628 (13.3%)
2,395 (14.0%)
12,316 (9.3%)
2,631 (10.8%)
53,496 (13.9%)
4,560 (15.7%)
86,440 (12.9%)
9,586 (13.6%)
-0.02
Use of lithium; n (%)
183 (0.1%)
23 (0.1%)
171 (0.1%)
13 (0.1%)
395 (0.1%)
27 (0.1%)
749 (0.1%)
063 (0.1%)
0.00
Use of Benzos; n (%)
12,618 (8.1%)
1,545 (9.0%)
10,457 (7.9%)
2,066 (8.5%)
37,940 (9.8%)
2,876 (9.9%)
61,015 (9.1%)
6,487 (9.2%)
0.00
Use of anxiolytics/hypnotics; n (%)
6,385 (4.1%)
938 (5.5%)
6,064 (4.6%)
1,394 (5.7%)
17,827 (4.6%)
1,653 (5.7%)
30,276 (4.5%)
3,985 (5.7%)
-0.05
Use of dementia meds; n (%)
3,210 (2.1%)
113 (0.7%)
1,591 (1.2%)
88 (0.4%)
15,947 (4.1%)
791 (2.7%)
20,748 (3.1%)
992 (1.4%)
0.11
Use of antiparkinsonian meds; n (%)
2,966 (1.9%)
338 (2.0%)
1,934 (1.5%)
385 (1.6%)
10,222 (2.7%)
859 (3.0%)
15,122 (2.2%)
1,582 (2.2%)
0.00
Any use of pramlintide; n (%)
3 (0.0%)
28 (0.2%)
22 (0.0%)
43 (0.2%)
22 (0.0%)
35 (0.1%)
047 (0.0%)
106 (0.2%)
-0.06
Any use of 1st generation sulfonylureas; n (%)
18 (0.0%)
2 (0.0%)
57 (0.0%)
1 (0.0%)
**
**
**
**
**
Entresto (sacubitril/valsartan); n (%)
182 (0.1%)
8 (0.0%)
45 (0.0%)
6 (0.0%)
**
**
**
**
**
Initiation as monotherapy  Copy; n (%)
16,688 (10.8%)
1,198 (7.0%)
12,296 (9.3%)
1,306 (5.4%)
39,187 (10.2%)
1,233 (4.3%)
68,171 (10.1%)
3,737 (5.3%)
0.18
Labs
                                       286,926                                           41,472 
Lab values- HbA1c (%) ; n (%)
60,079 (38.8%)
7,406 (43.2%)
8,994 (6.8%)
1,531 (6.3%)
N/A
N/A
69,073 (24.1%)
8,937 (21.5%)
0.06
Lab values- HbA1c (%) (within 3 months) ; n (%)
46,986 (30.3%)
6,068 (35.4%)
7,101 (5.4%)
1,306 (5.4%)
N/A
N/A
54,087 (18.9%)
7,374 (17.8%)
0.03
Lab values- HbA1c (%) (within 6 months) ; n (%)
60,079 (38.8%)
7,406 (43.2%)
8,994 (6.8%)
1,531 (6.3%)
N/A
N/A
69,073 (24.1%)
8,937 (21.5%)
0.06
Table 1

Lab values- BNP; n (%)
984 (0.6%)
101 (0.6%)
131 (0.1%)
14 (0.1%)
N/A
N/A
1,115 (0.4%)
115 (0.3%)
0.02
Lab values- BNP (within 3 months); n (%)
593 (0.4%)
65 (0.4%)
79 (0.1%)
9 (0.0%)
N/A
N/A
672 (0.2%)
074 (0.2%)
0.00
Lab values- BNP (within 6 months); n (%)
984 (0.6%)
101 (0.6%)
131 (0.1%)
14 (0.1%)
N/A
N/A
1,115 (0.4%)
115 (0.3%)
0.02
Lab values- BUN (mg/dl); n (%)
59,127 (38.2%)
7,320 (42.7%)
7,741 (5.9%)
1,426 (5.9%)
N/A
N/A
66,868 (23.3%)
8,746 (21.1%)
0.05
Lab values- BUN (mg/dl) (within 3 months); n (%)
45,566 (29.4%)
5,834 (34.0%)
5,886 (4.5%)
1,167 (4.8%)
N/A
N/A
51,452 (17.9%)
7,001 (16.9%)
0.03
Lab values- BUN (mg/dl) (within 6 months); n (%)
59,127 (38.2%)
7,320 (42.7%)
7,741 (5.9%)
1,426 (5.9%)
N/A
N/A
66,868 (23.3%)
8,746 (21.1%)
0.05
Lab values- Creatinine (mg/dl) ; n (%)
60,630 (39.1%)
7,582 (44.2%)
8,186 (6.2%)
1,576 (6.5%)
N/A
N/A
68,816 (24.0%)
9,158 (22.1%)
0.05
Lab values- Creatinine (mg/dl) (within 3 months) ; n (%)
46,724 (30.2%)
6,043 (35.2%)
6,236 (4.7%)
1,301 (5.3%)
N/A
N/A
52,960 (18.5%)
7,344 (17.7%)
0.02
Lab values- Creatinine (mg/dl) (within 6 months) ; n (%)
60,630 (39.1%)
7,582 (44.2%)
8,186 (6.2%)
1,576 (6.5%)
N/A
N/A
68,816 (24.0%)
9,158 (22.1%)
0.05
Lab values- HDL level (mg/dl); n (%)
50,020 (32.3%)
6,461 (37.7%)
7,994 (6.1%)
1,439 (5.9%)
N/A
N/A
58,014 (20.2%)
7,900 (19.0%)
0.03
Lab values- HDL level (mg/dl) (within 3 months); n (%)
36,675 (23.7%)
4,910 (28.6%)
5,881 (4.5%)
1,126 (4.6%)
N/A
N/A
42,556 (14.8%)
6,036 (14.6%)
0.01
Lab values- HDL level (mg/dl) (within 6 months); n (%)
50,020 (32.3%)
6,461 (37.7%)
7,994 (6.1%)
1,439 (5.9%)
N/A
N/A
58,014 (20.2%)
7,900 (19.0%)
0.03
Lab values- LDL level (mg/dl) ; n (%)
51,820 (33.5%)
6,667 (38.9%)
8,382 (6.3%)
1,463 (6.0%)
N/A
N/A
60,202 (21.0%)
8,130 (19.6%)
0.03
Lab values- LDL level (mg/dl) (within 3 months) ; n (%)
37,965 (24.5%)
5,085 (29.6%)
6,157 (4.7%)
1,149 (4.7%)
N/A
N/A
44,122 (15.4%)
6,234 (15.0%)
0.01
Lab values- LDL level (mg/dl) (within 6 months) ; n (%)
51,820 (33.5%)
6,667 (38.9%)
8,382 (6.3%)
1,463 (6.0%)
N/A
N/A
60,202 (21.0%)
8,130 (19.6%)
0.03
Lab values- NT-proBNP; n (%)
153 (0.1%)
9 (0.1%)
12 (0.0%)
0 (0.0%)
N/A
N/A
165 (0.1%)
9 (0.0%)
0.04
Lab values- NT-proBNP (within 3 months); n (%)
95 (0.1%)
5 (0.0%)
6 (0.0%)
0 (0.0%)
N/A
N/A
101 (0.0%)
5 (0.0%)
-
Lab values- NT-proBNP (within 6 months); n (%)
153 (0.1%)
9 (0.1%)
12 (0.0%)
0 (0.0%)
N/A
N/A
165 (0.1%)
9 (0.0%)
-
Lab values- Total cholesterol (mg/dl) ; n (%)
50,792 (32.8%)
6,592 (38.4%)
7,701 (5.8%)
1,444 (5.9%)
N/A
N/A
58,493 (20.4%)
8,036 (19.4%)
0.03
Lab values- Total cholesterol (mg/dl) (within 3 months) ; n 
(%)
37,250 (24.0%)
5,024 (29.3%)
5,639 (4.3%)
1,134 (4.7%)
N/A
N/A
42,889 (14.9%)
6,158 (14.8%)
0.00
Lab values- Total cholesterol (mg/dl) (within 6 months) ; n 
(%)
50,792 (32.8%)
6,592 (38.4%)
7,701 (5.8%)
1,444 (5.9%)
N/A
N/A
58,493 (20.4%)
8,036 (19.4%)
0.03
Lab values- Triglyceride level (mg/dl); n (%)
50,177 (32.4%)
6,549 (38.2%)
7,861 (6.0%)
1,423 (5.9%)
N/A
N/A
58,038 (20.2%)
7,972 (19.2%)
0.03
Lab values- Triglyceride level (mg/dl) (within 3 months); n 
(%)
36,827 (23.8%)
4,987 (29.1%)
5,788 (4.4%)
1,120 (4.6%)
N/A
N/A
42,615 (14.9%)
6,107 (14.7%)
0.01
Lab values- Triglyceride level (mg/dl) (within 6 months); n 
(%)
50,177 (32.4%)
6,549 (38.2%)
7,861 (6.0%)
1,423 (5.9%)
N/A
N/A
58,038 (20.2%)
7,972 (19.2%)
0.03
Lab result number- HbA1c (%) mean (only 2 to 20 
included) 
59,675
                                         
7,362
                                            
8,091
                                            
1,482
                                            
N/A
N/A                                           67,766                                              8,844 
...mean (sd)
8.19 (1.84)
8.51 (1.76)
8.39 (1.91)
8.53 (1.75)
N/A
N/A
8.21 (1.85)
8.51 (1.76)
-0.17
...median [IQR]
7.75 [6.93, 9.00]
8.10 [7.25, 9.47]
7.95 [7.00, 9.30]
8.10 [7.30, 9.40]
N/A
N/A
7.77 (1.85)
8.10 (1.76)
-0.18
...Missing; n (%)
95,211 (61.5%)
9,792 (57.1%)
123,949 (93.9%)
22,836 (93.9%)
N/A
N/A
219,160 (76.4%)
32,628 (78.7%)
-0.06
Lab result number- BNP mean 
984
                                                
101
                                                
131
                                                
14
                                                   
N/A
N/A                                              1,115                                                  115 
...mean (sd)
184.36 (301.56)
69.43 (79.37)
262.73 (698.20)
535.59 (1,297.93)
N/A
N/A
193.57 (370.65)
126.18 (448.51)
0.16
...median [IQR]
77.10 [29.92, 204.97]
41.30 [18.65, 86.70]
61.00 [30.00, 216.00]
55.50 [16.65, 170.65]
N/A
N/A
#VALUE!
#VALUE!
#VALUE!
...Missing; n (%)
153,902 (99.4%)
17,053 (99.4%)
131,909 (99.9%)
24,304 (99.9%)
N/A
N/A
285,811 (99.6%)
41,357 (99.7%)
-0.02
Lab result number- BUN (mg/dl) mean 
                                          59,127                                              7,320                                              7,741                                              1,426 
N/A
N/A                                           66,868                                              8,746 
...mean (sd)
18.65 (8.00)
16.63 (5.60)
1,108.21 (12,786.12)
2,280.99 (18,384.49)
N/A
N/A
144.78 (4350.21)
385.82 (7422.14)
-0.04
...median [IQR]
17.00 [13.50, 22.00]
16.00 [13.00, 19.00]
16.00 [13.00, 20.00]
16.00 [13.00, 19.00]
N/A
N/A
#VALUE!
#VALUE!
#VALUE!
...Missing; n (%)
95,759 (61.8%)
9,834 (57.3%)
124,299 (94.1%)
22,892 (94.1%)
N/A
N/A
220,058 (76.7%)
32,726 (78.9%)
-0.05
Lab result number- Creatinine (mg/dl) mean (only 0.1 to 
15 included) 
                                          60,232                                              7,531                                              7,231                                              1,439 
N/A
N/A                                           67,463                                              8,970 
...mean (sd)
1.04 (0.40)
0.92 (0.24)
1.00 (0.36)
0.93 (0.23)
N/A
N/A
1.04 (0.40)
0.92 (0.24)
0.36
...median [IQR]
0.95 [0.79, 1.18]
0.89 [0.76, 1.04]
0.95 [0.79, 1.10]
0.90 [0.76, 1.05]
N/A
N/A
0.95 (0.40)
0.89 (0.24)
0.18
...Missing; n (%)
94,654 (61.1%)
9,623 (56.1%)
124,809 (94.5%)
22,879 (94.1%)
N/A
N/A
219,463 (76.5%)
32,502 (78.4%)
-0.05
Lab result number- HDL level (mg/dl) mean (only =<5000 
included) 
                                          50,020                                              6,461                                              7,944                                              1,422 
N/A
N/A                                           57,964                                              7,883 
...mean (sd)
46.42 (13.62)
45.25 (13.20)
44.50 (14.95)
46.24 (105.86)
N/A
N/A
46.16 (13.81)
45.43 (46.52)
0.02
...median [IQR]
44.50 [37.00, 54.00]
43.00 [36.00, 52.00]
43.00 [36.00, 52.00]
42.50 [35.00, 50.06]
N/A
N/A
44.29 (13.81)
42.91 (46.52)
0.04
...Missing; n (%)
104,866 (67.7%)
10,693 (62.3%)
124,096 (94.0%)
22,896 (94.2%)
N/A
N/A
228,962 (79.8%)
33,589 (81.0%)
-0.03
Lab result number- LDL level (mg/dl) mean (only =<5000 
included) 
                                          50,646                                              6,539                                              7,492                                              1,290 
N/A
N/A                                           58,138                                              7,829 
...mean (sd)
87.95 (39.92)
84.31 (39.29)
90.16 (42.99)
86.14 (40.59)
N/A
N/A
88.23 (40.33)
84.61 (39.51)
0.09
...median [IQR]
85.00 [64.00, 111.00]
82.00 [61.00, 106.00]
89.00 [66.00, 115.00]
85.00 [62.50, 110.50]
N/A
N/A
85.52 (40.33)
82.49 (39.51)
0.08
...Missing; n (%)
104,240 (67.3%)
10,615 (61.9%)
124,548 (94.3%)
23,028 (94.7%)
N/A
N/A
228,788 (79.7%)
33,643 (81.1%)
-0.04
Lab result number- Total cholesterol (mg/dl) mean (only 
=<5000 included) 
                                          50,753                                              6,586                                              7,649                                              1,425 
N/A
N/A                                           58,402                                              8,011 
...mean (sd)
174.22 (46.76)
172.48 (46.71)
175.10 (52.79)
171.47 (55.16)
N/A
N/A
174.34 (47.59)
172.30 (48.32)
0.04
...median [IQR]
168.00 [143.00, 199.00]
166.50 [142.00, 195.50]
172.00 [146.00, 204.00]
169.00 [143.00, 196.00]
N/A
N/A
168.52 (47.59)
166.94 (48.32)
0.03
...Missing; n (%)
104,133 (67.2%)
10,568 (61.6%)
124,391 (94.2%)
22,893 (94.1%)
N/A
N/A
228,524 (79.6%)
33,461 (80.7%)
-0.03
Table 1

Lab result number- Triglyceride level (mg/dl) mean (only 
=<5000 included) 
                                          50,170                                              6,548                                              7,808                                              1,404 
N/A
N/A                                           57,978                                              7,952 
...mean (sd)
184.72 (150.34)
197.99 (180.75)
187.17 (163.73)
195.06 (186.08)
N/A
N/A
185.05 (152.21)
197.47 (181.71)
-0.07
...median [IQR]
151.00 [108.00, 216.00]
157.75 [112.00, 227.00]
150.00 [105.00, 219.25]
158.75 [111.00, 227.00]
N/A
N/A
150.87 (152.21)
157.93 (181.71)
-0.04
...Missing; n (%)
104,716 (67.6%)
10,606 (61.8%)
124,232 (94.1%)
22,914 (94.2%)
N/A
N/A
228,948 (79.8%)
33,520 (80.8%)
-0.03
Lab result number- Hemoglobin mean (only >0 included)
                                          40,207                                              4,846                                              5,256                                                  907 
N/A
N/A                                           45,463                                              5,753 
...mean (sd)
13.52 (1.64)
14.06 (1.55)
9,789.51 (284,520.72)
13,220.12 (332,411.46)
N/A
N/A
1143.73 (96735.42)
2096.09 (131949.02)
-0.01
...median [IQR]
13.55 [12.45, 14.60]
14.10 [13.00, 15.10]
13.70 [12.60, 14.80]
13.95 [12.90, 15.00]
N/A
N/A
#VALUE!
#VALUE!
#VALUE!
...Missing; n (%)
114,679 (74.0%)
12,308 (71.8%)
126,784 (96.0%)
23,411 (96.3%)
N/A
N/A
241,463 (84.2%)
35,719 (86.1%)
-0.05
Lab result number- Serum sodium mean (only > 90 and < 
190 included)
                                          58,728                                              7,403                                              7,402                                              1,411 
N/A
N/A                                           66,130                                              8,814 
...mean (sd)
139.42 (2.80)
139.27 (2.61)
138.86 (2.72)
139.05 (2.40)
N/A
N/A
139.36 (2.79)
139.23 (2.58)
0.05
...median [IQR]
139.67 [138.00, 141.00]
139.00 [138.00, 141.00]
139.00 [137.00, 141.00]
139.00 [138.00, 140.67]
N/A
N/A
139.60 (2.79)
139.00 (2.58)
0.22
...Missing; n (%)
96,158 (62.1%)
9,751 (56.8%)
124,638 (94.4%)
22,907 (94.2%)
N/A
N/A
220,796 (77.0%)
32,658 (78.7%)
-0.04
Lab result number- Albumin mean (only >0 and <=10 
included)
                                          54,335                                              6,987                                              6,383                                              1,182 
N/A
N/A                                           60,718                                              8,169 
...mean (sd)
4.26 (0.31)
4.31 (0.30)
4.10 (0.73)
4.17 (0.69)
N/A
N/A
4.24 (0.38)
4.29 (0.38)
-0.13
...median [IQR]
4.30 [4.10, 4.50]
4.30 [4.10, 4.50]
4.20 [4.00, 4.40]
4.30 [4.00, 4.50]
N/A
N/A
4.29 (0.38)
4.30 (0.38)
-0.03
...Missing; n (%)
100,551 (64.9%)
10,167 (59.3%)
125,657 (95.2%)
23,136 (95.1%)
N/A
N/A
226,208 (78.8%)
33,303 (80.3%)
-0.04
Lab result number- Glucose (fasting or random) mean 
(only 10-1000 included)
                                          58,552                                              7,391                                              7,387                                              1,393 
N/A
N/A                                           65,939                                              8,784 
...mean (sd)
174.40 (73.35)
178.35 (69.83)
182.10 (77.32)
175.89 (63.14)
N/A
N/A
175.26 (73.81)
177.96 (68.82)
-0.04
...median [IQR]
156.00 [126.00, 203.00]
162.00 [130.00, 211.00]
162.00 [130.00, 215.00]
163.00 [131.50, 208.00]
N/A
N/A
156.67 (73.81)
162.16 (68.82)
-0.08
...Missing; n (%)
96,334 (62.2%)
9,763 (56.9%)
124,653 (94.4%)
22,925 (94.3%)
N/A
N/A
220,987 (77.0%)
32,688 (78.8%)
-0.04
Lab result number- Potassium mean (only 1-7 included)
                                          60,268                                              7,541                                              7,444                                              1,371 
N/A
N/A                                           67,712                                              8,912 
...mean (sd)
4.46 (0.44)
4.44 (0.40)
4.32 (0.46)
4.36 (0.41)
N/A
N/A
4.44 (0.44)
4.43 (0.40)
0.02
...median [IQR]
4.45 [4.20, 4.70]
4.40 [4.20, 4.70]
4.30 [4.00, 4.60]
4.38 [4.10, 4.60]
N/A
N/A
4.43 (0.44)
4.40 (0.40)
0.07
...Missing; n (%)
94,618 (61.1%)
9,613 (56.0%)
124,596 (94.4%)
22,947 (94.4%)
N/A
N/A
219,214 (76.4%)
32,560 (78.5%)
-0.05
Comorbidity Scores
CCI (180 days)- ICD9 and ICD10 
...mean (sd)
2.48 (1.68)
2.06 (1.28)
1.84 (1.27)
1.65 (0.97)
2.61 (1.79)
2.37 (1.51)
2.43 (1.67)
2.05 (1.29)
0.25
...median [IQR]
2.00 [1.00, 3.00]
2.00 [1.00, 2.00]
1.00 [1.00, 2.00]
1.00 [1.00, 2.00]
2.00 [1.00, 4.00]
2.00 [1.00, 3.00]
1.80 (1.67)
1.65 (1.29)
0.10
Frailty Score: Qualitative Version 365 days as Categories, 
...0; n (%)
97,586 (63.0%)
11,069 (64.5%)
71,771 (54.4%)
12,999 (53.5%)
159,513 (41.4%)
13,058 (45.0%)
328,870 (48.9%)
37,126 (52.7%)
-0.08
...1 to 2; n (%)
42,109 (27.2%)
4,734 (27.6%)
45,704 (34.6%)
9,121 (37.5%)
136,252 (35.4%)
10,120 (34.9%)
224,065 (33.3%)
23,975 (34.0%)
-0.01
...3 or more; n (%)
15,191 (9.8%)
1,351 (7.9%)
14,565 (11.0%)
2,198 (9.0%)
89,667 (23.3%)
5,809 (20.0%)
119,423 (17.8%)
9,358 (13.3%)
0.12
Frailty Score: Empirical Version 365 days as Categories, 
...< 0.12908; n (%)
43,729 (28.2%)
5,999 (35.0%)
38,804 (29.4%)
8,113 (33.4%)
51,925 (13.5%)
4,669 (16.1%)
134,458 (20.0%)
18,781 (26.7%)
-0.16
...0.12908 - 0.1631167; n (%)
55,491 (35.8%)
6,402 (37.3%)
50,669 (38.4%)
9,645 (39.7%)
111,334 (28.9%)
8,922 (30.8%)
217,494 (32.3%)
24,969 (35.4%)
-0.07
...>= 0.1631167; n (%)
55,666 (35.9%)
4,753 (27.7%)
42,567 (32.2%)
6,560 (27.0%)
222,173 (57.6%)
15,396 (53.1%)
320,406 (47.7%)
26,709 (37.9%)
0.20
Non-Frailty; n (%)
86,446 (55.8%)
9,990 (58.2%)
65,874 (49.9%)
13,103 (53.9%)
20,611 (5.3%)
1,336 (4.6%)
172,931 (25.7%)
24,429 (34.7%)
-0.20
Frailty Score (mean): Qualitative Version 365 days, 
...mean (sd)
0.78 (1.42)
0.67 (1.20)
0.91 (1.42)
0.83 (1.20)
1.53 (1.95)
1.32 (1.69)
1.24 (1.74)
0.99 (1.42)
0.16
...median [IQR]
0.00 [0.00, 1.00]
0.00 [0.00, 1.00]
0.00 [0.00, 1.00]
0.00 [0.00, 1.00]
1.00 [0.00, 2.00]
1.00 [0.00, 2.00]
0.57 (1.74)
0.41 (1.42)
0.10
Frailty Score (mean): Empirical Version 365 days, 
...mean (sd)
0.16 (0.05)
0.15 (0.04)
0.15 (0.04)
0.14 (0.04)
0.19 (0.06)
0.18 (0.05)
0.18 (0.05)
0.16 (0.04)
0.44
...median [IQR]
0.15 [0.13, 0.18]
0.14 [0.12, 0.17]
0.14 [0.12, 0.17]
0.14 [0.12, 0.16]
0.17 [0.14, 0.21]
0.17 [0.14, 0.20]
0.16 (0.05)
0.15 (0.04)
0.22
Healthcare Utilization
Any hospitalization; n (%)
7,615 (4.9%)
403 (2.3%)
6,017 (4.6%)
501 (2.1%)
27,334 (7.1%)
1,128 (3.9%)
40,966 (6.1%)
2,032 (2.9%)
0.15
Any hospitalization within prior 30 days; n (%)
2,663 (1.7%)
63 (0.4%)
2,107 (1.6%)
77 (0.3%)
9,168 (2.4%)
186 (0.6%)
13,938 (2.1%)
326 (0.5%)
0.14
Any hospitalization during prior 31-180 days; n (%)
5,232 (3.4%)
341 (2.0%)
4,082 (3.1%)
428 (1.8%)
19,390 (5.0%)
964 (3.3%)
28,704 (4.3%)
1,733 (2.5%)
0.10
Endocrinologist Visit; n (%)
10,283 (6.6%)
2,944 (17.2%)
9,029 (6.8%)
4,320 (17.8%)
32,210 (8.4%)
5,395 (18.6%)
51,522 (7.7%)
12,659 (18.0%)
-0.31
Endocrinologist Visit (30 days prior); n (%)
6,054 (3.9%)
2,159 (12.6%)
5,613 (4.3%)
3,385 (13.9%)
18,533 (4.8%)
3,825 (13.2%)
30,200 (4.5%)
9,369 (13.3%)
-0.31
Endocrinologist Visit (31 to 180 days prior); n (%)
7,255 (4.7%)
2,095 (12.2%)
6,203 (4.7%)
3,089 (12.7%)
24,236 (6.3%)
4,125 (14.2%)
37,694 (5.6%)
9,309 (13.2%)
-0.26
Internal medicine/family medicine visits; n (%)
129,232 (83.4%)
12,121 (70.7%)
113,946 (86.3%)
21,262 (87.4%)
316,729 (82.2%)
23,915 (82.5%)
559,907 (83.3%)
57,298 (81.3%)
0.05
Internal medicine/family medicine visits (30 days prior) ; 
n (%)
95,398 (61.6%)
8,775 (51.2%)
85,543 (64.8%)
16,208 (66.7%)
220,852 (57.3%)
17,395 (60.0%)
401,793 (59.8%)
42,378 (60.1%)
-0.01
Internal medicine/family medicine visits (31 to 180 days 
prior) ; n (%)
107,756 (69.6%)
10,414 (60.7%)
89,803 (68.0%)
17,894 (73.6%)
266,263 (69.1%)
21,172 (73.0%)
463,822 (69.0%)
49,480 (70.2%)
-0.03
Cardiologist visit; n (%)
35,417 (22.9%)
3,293 (19.2%)
21,785 (16.5%)
4,133 (17.0%)
114,927 (29.8%)
8,307 (28.7%)
172,129 (25.6%)
15,733 (22.3%)
0.08
Number of Cardiologist visits (30 days prior); n (%)
12,163 (7.9%)
1,041 (6.1%)
7,375 (5.6%)
1,236 (5.1%)
38,495 (10.0%)
2,576 (8.9%)
58,033 (8.6%)
4,853 (6.9%)
0.06
Table 1

Number of Cardiologist visits (31 to 180 days prior); n (%)
29,585 (19.1%)
2,777 (16.2%)
18,012 (13.6%)
3,495 (14.4%)
98,325 (25.5%)
7,192 (24.8%)
145,922 (21.7%)
13,464 (19.1%)
0.06
Electrocardiogram ; n (%)
39,699 (25.6%)
3,920 (22.9%)
32,047 (24.3%)
5,731 (23.6%)
114,568 (29.7%)
8,455 (29.2%)
186,314 (27.7%)
18,106 (25.7%)
0.05
Use of glucose test strips; n (%)
4,705 (3.0%)
608 (3.5%)
4,168 (3.2%)
1,037 (4.3%)
11,116 (2.9%)
960 (3.3%)
19,989 (3.0%)
2,605 (3.7%)
-0.04
Dialysis; n (%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
000 (0.0%)
000 (0.0%)
#DIV/0!
Naive new user v8 Copy; n (%)
33,568 (21.7%)
1,869 (10.9%)
27,156 (20.6%)
2,032 (8.4%)
74,547 (19.3%)
1,975 (6.8%)
135,271 (20.1%)
5,876 (8.3%)
0.34
N antidiabetic drugs at index date  Copy
...mean (sd)
1.89 (0.73)
2.29 (0.88)
1.98 (0.76)
2.35 (0.90)
1.88 (0.74)
2.36 (0.89)
1.90 (0.74)
2.34 (0.89)
-0.54
...median [IQR]
2.00 [1.00, 2.00]
2.00 [2.00, 3.00]
2.00 [1.00, 2.00]
2.00 [2.00, 3.00]
2.00 [1.00, 2.00]
2.00 [2.00, 3.00]
2.00 (0.74)
2.00 (0.89)
0.00
number of different/distinct medication prescriptions
...mean (sd)
9.15 (4.15)
10.03 (4.47)
8.64 (3.92)
9.85 (4.23)
9.16 (3.98)
10.48 (4.44)
9.06 (4.01)
10.15 (4.38)
-0.26
...median [IQR]
8.00 [6.00, 11.00]
9.00 [7.00, 12.00]
8.00 [6.00, 11.00]
9.00 [7.00, 12.00]
9.00 [6.00, 11.00]10.00 [7.00, 13.00]
8.57 (4.01)
9.41 (4.38)
-0.20
Number of Hospitalizations
...mean (sd)
0.06 (0.27)
0.03 (0.17)
0.05 (0.24)
0.02 (0.16)
0.08 (0.34)
0.04 (0.23)
0.07 (0.31)
0.03 (0.19)
0.16
...median [IQR]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 (0.31)
0.00 (0.19)
0.00
Number of hospital days
...mean (sd)
0.29 (2.03)
0.11 (0.96)
0.26 (1.78)
0.10 (0.87)
0.51 (3.04)
0.23 (1.86)
0.41 (2.62)
0.16 (1.38)
0.12
...median [IQR]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 (2.62)
0.00 (1.38)
0.00
Number of Emergency Department (ED) visits 
...mean (sd)
0.32 (0.96)
0.21 (0.76)
0.10 (0.93)
0.04 (0.54)
0.43 (1.16)
0.31 (1.07)
0.34 (1.07)
0.19 (0.84)
0.16
...median [IQR]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 (1.07)
0.00 (0.84)
0.00
Number of Office visits
...mean (sd)
3.95 (3.11)
4.28 (3.09)
3.80 (3.07)
4.27 (3.11)
4.45 (3.52)
5.10 (3.63)
4.21 (3.34)
4.61 (3.33)
-0.12
...median [IQR]
3.00 [2.00, 5.00]
3.00 [2.00, 6.00]
3.00 [2.00, 5.00]
3.00 [2.00, 5.00]
4.00 [2.00, 6.00]
4.00 [3.00, 7.00]
3.57 (3.34)
3.41 (3.33)
0.05
Number of Endocrinologist visits
...mean (sd)
0.29 (1.68)
0.94 (3.31)
0.28 (1.62)
0.98 (3.45)
0.44 (2.45)
1.25 (4.77)
0.37 (2.15)
1.08 (4.02)
-0.22
...median [IQR]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 (2.15)
0.00 (4.02)
0.00
Number of internal medicine/family medicine visits
...mean (sd)
8.28 (11.20)
6.97 (10.95)
5.99 (7.55)
6.47 (7.65)
6.87 (9.22)
7.76 (10.04)
7.02 (9.42)
7.12 (9.53)
-0.01
...median [IQR]
5.00 [2.00, 11.00]
4.00 [0.00, 9.00]
4.00 [2.00, 8.00]
4.00 [2.00, 9.00]
4.00 [1.00, 9.00] 5.00 [2.00, 10.00]
4.23 (9.42)
4.41 (9.53)
-0.02
Number of Cardiologist visits
...mean (sd)
0.96 (2.84)
0.76 (2.44)
0.63 (2.23)
0.63 (2.15)
1.40 (3.79)
1.35 (3.65)
1.15 (3.33)
0.96 (2.92)
0.06
...median [IQR]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 1.00]
0.00 [0.00, 1.00]
0.00 (3.33)
0.00 (2.92)
0.00
Number electrocardiograms received 
...mean (sd)
0.45 (1.12)
0.35 (0.86)
0.40 (0.93)
0.35 (0.83)
0.55 (1.15)
0.50 (1.07)
0.50 (1.10)
0.41 (0.94)
0.09
...median [IQR]
0.00 [0.00, 1.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 1.00]
0.00 [0.00, 1.00]
0.00 (1.10)
0.00 (0.94)
0.00
Number of HbA1c tests ordered
...mean (sd)
1.20 (0.86)
1.36 (0.88)
1.00 (0.85)
1.30 (0.86)
1.30 (0.82)
1.56 (0.82)
1.22 (0.84)
1.42 (0.85)
-0.24
...median [IQR]
1.00 [1.00, 2.00]
1.00 [1.00, 2.00]
1.00 [0.00, 2.00]
1.00 [1.00, 2.00]
1.00 [1.00, 2.00]
2.00 [1.00, 2.00]
1.00 (0.84)
1.41 (0.85)
-0.49
Number of glucose tests ordered
...mean (sd)
0.39 (2.19)
0.44 (1.71)
0.32 (1.15)
0.40 (1.03)
0.34 (0.93)
0.48 (1.14)
0.35 (1.36)
0.44 (1.27)
-0.07
...median [IQR]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 (1.36)
0.00 (1.27)
0.00
Number of lipid tests ordered
...mean (sd)
0.92 (0.89)
1.07 (0.96)
0.83 (1.13)
1.07 (1.14)
0.93 (0.78)
1.13 (0.84)
0.91 (0.88)
1.09 (0.98)
-0.19
...median [IQR]
1.00 [0.00, 1.00]
1.00 [0.00, 2.00]
1.00 [0.00, 1.00]
1.00 [0.00, 2.00]
1.00 [0.00, 1.00]
1.00 [1.00, 2.00]
1.00 (0.88)
1.00 (0.98)
0.00
Number of creatinine tests ordered
...mean (sd)
0.04 (0.27)
0.03 (0.21)
0.06 (0.33)
0.04 (0.23)
0.07 (0.34)
0.07 (0.32)
0.06 (0.32)
0.05 (0.27)
0.03
...median [IQR]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 (0.32)
0.00 (0.27)
0.00
Number of BUN tests ordered
...mean (sd)
0.02 (0.20)
0.02 (0.16)
0.03 (0.23)
0.02 (0.17)
0.04 (0.28)
0.04 (0.26)
0.03 (0.25)
0.03 (0.21)
0.00
...median [IQR]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 (0.25)
0.00 (0.21)
0.00
Number of tests for microalbuminuria
...mean (sd)
0.77 (1.14)
0.85 (1.19)
0.58 (0.99)
0.76 (1.12)
0.44 (0.67)
0.54 (0.73)
0.54 (0.87)
0.69 (1.00)
-0.16
...median [IQR]
0.00 [0.00, 2.00]
0.00 [0.00, 2.00]
0.00 [0.00, 1.00]
0.00 [0.00, 2.00]
0.00 [0.00, 1.00]
0.00 [0.00, 1.00]
0.00 (0.87)
0.00 (1.00)
0.00
Total N distinct ICD9/ICD10 diagnoses at the 3rd digit 
level Copy
...mean (sd)
6.00 (6.67)
5.41 (6.00)
2.52 (4.05)
2.02 (3.24)
5.62 (7.42)
5.82 (6.93)
5.10 (6.71)
4.41 (5.67)
0.11
...median [IQR]
5.00 [0.00, 9.00]
5.00 [0.00, 8.00]
0.00 [0.00, 4.00]
0.00 [0.00, 4.00]
4.00 [0.00, 9.00]
4.00 [0.00, 9.00]
3.44 (6.71)
2.86 (5.67)
0.09
Use of thiazide; n (%)
21,636 (14.0%)
2,104 (12.3%)
17,561 (13.3%)
2,846 (11.7%)
59,136 (15.3%)
4,124 (14.2%)
98,333 (14.6%)
9,074 (12.9%)
0.05
Use of beta blockers; n (%)
64,047 (41.4%)
6,162 (35.9%)
49,659 (37.6%)
8,563 (35.2%)
190,922 (49.5%)
13,995 (48.3%)
304,628 (45.3%)
28,720 (40.8%)
0.09
Use of calcium channel blockers; n (%)
51,925 (33.5%)
4,913 (28.6%)
41,303 (31.3%)
6,991 (28.7%)
139,264 (36.1%)
9,858 (34.0%)
232,492 (34.6%)
21,762 (30.9%)
0.08
Table 1

Variable
Reference- 2nd 
Generation SUs
Exposure- Canagliflozin
Reference- 2nd 
Generation SUs
Exposure- Canagliflozin
Reference- 2nd 
Generation SUs
Exposure- Canagliflozin
Reference- 2nd 
Generation SUs
Exposure- Canagliflozin
St. Diff.
Number of patients
16740
16740
23265
23265
28845
28845                                           68,850                                           68,850 
Age
...mean (sd)
62.01 (8.13)
62.11 (7.84)
59.18 (6.78)
59.28 (6.44)
70.96 (5.29)
71.04 (5.27)
64.80 (6.58)
64.89 (6.37)
-0.01
...median [IQR]
61.00 [55.00, 68.00]
61.00 [56.00, 68.00]
58.00 [54.00, 63.00]
59.00 [54.00, 63.00]
70.00 [67.00, 74.00]
70.00 [67.00, 74.00]
63.76 (6.58)
64.09 (6.37)
-0.05
Age categories 
...18 - 54; n (%)
3,698 (22.1%)
3,224 (19.3%)
6,341 (27.3%)
5,909 (25.4%)
0 (0.0%)
0 (0.0%)
10,039 (14.6%)
9,133 (13.3%)
0.04
...55 - 64; n (%)
6,485 (38.7%)
7,238 (43.2%)
13,228 (56.9%)
13,588 (58.4%)
355 (1.2%)
326 (1.1%)
20,068 (29.1%)
21,152 (30.7%)
-0.03
...65 - 74; n (%)
5,339 (31.9%)
5,124 (30.6%)
2,904 (12.5%)
3,121 (13.4%)
22,248 (77.1%)
22,245 (77.1%)
30,491 (44.3%)
30,490 (44.3%)
0.00
...>= 75; n (%)
1,218 (7.3%)
1,154 (6.9%)
792 (3.4%)
647 (2.8%)
6,242 (21.6%)
6,274 (21.8%)
8,252 (12.0%)
8,075 (11.7%)
0.01
Gender 
...Males; n (%)
9,326 (55.7%)
9,329 (55.7%)
12,867 (55.3%)
12,977 (55.8%)
14,338 (49.7%)
14,294 (49.6%)
36,531 (53.1%)
36,600 (53.2%)
0.00
...Females; n (%)
7,414 (44.3%)
7,411 (44.3%)
10,398 (44.7%)
10,288 (44.2%)
14,507 (50.3%)
14,551 (50.4%)
32,319 (46.9%)
32,250 (46.8%)
0.00
Race 
...White; n (%)
N/A
N/A
N/A
N/A
23,182 (80.4%)
23,167 (80.3%)
23,182 (80.4%)
23,167 (80.3%)
0.00
...Black; n (%)
N/A
N/A
N/A
N/A
2,305 (8.0%)
2,349 (8.1%)
2,305 (8.0%)
2,349 (8.1%)
0.00
...Asian; n (%)
N/A
N/A
N/A
N/A
1,028 (3.6%)
1,033 (3.6%)
1,028 (3.6%)
1,033 (3.6%)
0.00
...Hispanic; n (%)
N/A
N/A
N/A
N/A
989 (3.4%)
979 (3.4%)
989 (3.4%)
979 (3.4%)
0.00
...North American Native; n (%)
N/A
N/A
N/A
N/A
117 (0.4%)
116 (0.4%)
117 (0.4%)
116 (0.4%)
0.00
...Other/Unknown; n (%)
N/A
N/A
N/A
N/A
1,224 (4.2%)
1,201 (4.2%)
1,224 (4.2%)
1,201 (4.2%)
0.00
Region   (lumping missing&other category with 
West)
...Northeast; n (%)
1,493 (8.9%)
1,442 (8.6%)
4,400 (18.9%)
4,366 (18.8%)
5,438 (18.9%)
5,436 (18.8%)
11,331 (16.5%)
11,244 (16.3%)
0.01
...South; n (%)
8,914 (53.2%)
8,950 (53.5%)
4,094 (17.6%)
4,131 (17.8%)
12,680 (44.0%)
12,557 (43.5%)
25,688 (37.3%)
25,638 (37.2%)
0.00
...Midwest; n (%)
3,472 (20.7%)
3,479 (20.8%)
12,357 (53.1%)
12,331 (53.0%)
5,681 (19.7%)
5,860 (20.3%)
21,510 (31.2%)
21,670 (31.5%)
-0.01
...West; n (%)
2,861 (17.1%)
2,869 (17.1%)
2,142 (9.2%)
2,164 (9.3%)
5,046 (17.5%)
4,992 (17.3%)
10,049 (14.6%)
10,025 (14.6%)
0.00
...Unknown+missing; n (%)
N/A
N/A
272 (1.2%)
273 (1.2%)
N/A
N/A
272 (1.2%)
273 (1.2%)
0.00
CV Covariates
Ischemic heart disease; n (%)
2,400 (14.3%)
2,439 (14.6%)
2,833 (12.2%)
2,838 (12.2%)
7,091 (24.6%)
7,225 (25.0%)
12,324 (17.9%)
12,502 (18.2%)
-0.01
Acute MI; n (%)
46 (0.3%)
38 (0.2%)
62 (0.3%)
56 (0.2%)
111 (0.4%)
100 (0.3%)
219 (0.3%)
194 (0.3%)
0.00
ACS/unstable angina; n (%)
75 (0.4%)
74 (0.4%)
84 (0.4%)
78 (0.3%)
146 (0.5%)
147 (0.5%)
305 (0.4%)
299 (0.4%)
0.00
Old MI; n (%)
266 (1.6%)
282 (1.7%)
167 (0.7%)
191 (0.8%)
701 (2.4%)
697 (2.4%)
1,134 (1.6%)
1,170 (1.7%)
-0.01
Stable angina; n (%)
331 (2.0%)
344 (2.1%)
327 (1.4%)
308 (1.3%)
849 (2.9%)
855 (3.0%)
1,507 (2.2%)
1,507 (2.2%)
0.00
Coronary atherosclerosis and other forms of chronic 
ischemic heart disease; n (%)
2,260 (13.5%)
2,311 (13.8%)
2,679 (11.5%)
2,680 (11.5%)
6,812 (23.6%)
6,919 (24.0%)
11,751 (17.1%)
11,910 (17.3%)
-0.01
Other atherosclerosis with ICD10  Copy; n (%)
66 (0.4%)
71 (0.4%)
89 (0.4%)
130 (0.6%)
271 (0.9%)
336 (1.2%)
426 (0.6%)
537 (0.8%)
-0.02
Previous cardiac procedure (CABG or PTCA or Stent) ; 
n (%)
26 (0.2%)
17 (0.1%)
27 (0.1%)
31 (0.1%)
51 (0.2%)
52 (0.2%)
104 (0.2%)
100 (0.1%)
0.03
History of CABG or PTCA; n (%)
502 (3.0%)
496 (3.0%)
344 (1.5%)
326 (1.4%)
1,690 (5.9%)
1,666 (5.8%)
2,536 (3.7%)
2,488 (3.6%)
0.01
Any stroke; n (%)
447 (2.7%)
446 (2.7%)
432 (1.9%)
464 (2.0%)
1,546 (5.4%)
1,579 (5.5%)
2,425 (3.5%)
2,489 (3.6%)
-0.01
Ischemic stroke (w and w/o mention of cerebral 
infarction); n (%)
441 (2.6%)
443 (2.6%)
432 (1.9%)
459 (2.0%)
1,544 (5.4%)
1,571 (5.4%)
2,417 (3.5%)
2,473 (3.6%)
-0.01
Hemorrhagic stroke; n (%)
6 (0.0%)
5 (0.0%)
1 (0.0%)
6 (0.0%)
**
**
**
**
**
TIA; n (%)
55 (0.3%)
52 (0.3%)
51 (0.2%)
44 (0.2%)
171 (0.6%)
152 (0.5%)
277 (0.4%)
248 (0.4%)
0.00
Other cerebrovascular disease; n (%)
121 (0.7%)
109 (0.7%)
104 (0.4%)
96 (0.4%)
314 (1.1%)
331 (1.1%)
539 (0.8%)
536 (0.8%)
0.00
Late effects of cerebrovascular disease; n (%)
95 (0.6%)
75 (0.4%)
39 (0.2%)
49 (0.2%)
224 (0.8%)
244 (0.8%)
358 (0.5%)
368 (0.5%)
0.00
Cerebrovascular procedure; n (%)
6 (0.0%)
5 (0.0%)
2 (0.0%)
4 (0.0%)
13 (0.0%)
17 (0.1%)
021 (0.0%)
026 (0.0%)
#DIV/0!
Heart failure (CHF); n (%)
626 (3.7%)
624 (3.7%)
463 (2.0%)
463 (2.0%)
1,993 (6.9%)
1,994 (6.9%)
3,082 (4.5%)
3,081 (4.5%)
0.00
Peripheral Vascular Disease (PVD) or PVD Surgery ; n 
(%)
705 (4.2%)
715 (4.3%)
610 (2.6%)
610 (2.6%)
2,231 (7.7%)
2,292 (7.9%)
3,546 (5.2%)
3,617 (5.3%)
0.00
Atrial fibrillation; n (%)
703 (4.2%)
724 (4.3%)
745 (3.2%)
745 (3.2%)
2,434 (8.4%)
2,409 (8.4%)
3,882 (5.6%)
3,878 (5.6%)
0.00
Other cardiac dysrhythmia; n (%)
873 (5.2%)
880 (5.3%)
744 (3.2%)
784 (3.4%)
2,760 (9.6%)
2,761 (9.6%)
4,377 (6.4%)
4,425 (6.4%)
0.00
Cardiac conduction disorders; n (%)
231 (1.4%)
224 (1.3%)
223 (1.0%)
206 (0.9%)
815 (2.8%)
751 (2.6%)
1,269 (1.8%)
1,181 (1.7%)
0.01
Other CVD; n (%)
975 (5.8%)
995 (5.9%)
1,144 (4.9%)
1,136 (4.9%)
3,065 (10.6%)
3,147 (10.9%)
5,184 (7.5%)
5,278 (7.7%)
-0.01
Diabetes-related complications
Diabetic retinopathy; n (%)
893 (5.3%)
950 (5.7%)
894 (3.8%)
931 (4.0%)
2,088 (7.2%)
2,176 (7.5%)
3,875 (5.6%)
4,057 (5.9%)
-0.01
Diabetes with other ophthalmic manifestations; n 
(%)
89 (0.5%)
98 (0.6%)
544 (2.3%)
556 (2.4%)
829 (2.9%)
817 (2.8%)
1,462 (2.1%)
1,471 (2.1%)
0.00
Retinal detachment, vitreous hemorrhage, 
vitrectomy; n (%)
65 (0.4%)
60 (0.4%)
62 (0.3%)
60 (0.3%)
133 (0.5%)
118 (0.4%)
260 (0.4%)
238 (0.3%)
0.02
Retinal laser coagulation therapy; n (%)
102 (0.6%)
102 (0.6%)
106 (0.5%)
109 (0.5%)
182 (0.6%)
202 (0.7%)
390 (0.6%)
413 (0.6%)
0.00
Occurrence of Diabetic Neuropathy  Copy; n (%)
2,833 (16.9%)
2,850 (17.0%)
2,441 (10.5%)
2,499 (10.7%)
5,678 (19.7%)
5,713 (19.8%)
10,952 (15.9%)
11,062 (16.1%)
-0.01
 PS-matched
MarketScan
Medicare
POOLED
Optum
Table 1

Occurrence of diabetic nephropathy  with ICD10 
Copy; n (%)
1,592 (9.5%)
1,610 (9.6%)
1,235 (5.3%)
1,208 (5.2%)
2,370 (8.2%)
2,334 (8.1%)
5,197 (7.5%)
5,152 (7.5%)
0.00
Hypoglycemia ; n (%)
359 (2.1%)
342 (2.0%)
487 (2.1%)
533 (2.3%)
633 (2.2%)
656 (2.3%)
1,479 (2.1%)
1,531 (2.2%)
-0.01
Hyperglycemia; n (%)
581 (3.5%)
578 (3.5%)
638 (2.7%)
616 (2.6%)
1,019 (3.5%)
1,016 (3.5%)
2,238 (3.3%)
2,210 (3.2%)
0.01
Disorders of fluid electrolyte and acid-base balance; n 
(%)
569 (3.4%)
541 (3.2%)
496 (2.1%)
515 (2.2%)
1,213 (4.2%)
1,221 (4.2%)
2,278 (3.3%)
2,277 (3.3%)
0.00
Diabetic ketoacidosis; n (%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
000 (0.0%)
000 (0.0%)
#DIV/0!
Hyperosmolar hyperglycemic nonketotic syndrome 
(HONK); n (%)
89 (0.5%)
74 (0.4%)
74 (0.3%)
71 (0.3%)
149 (0.5%)
141 (0.5%)
312 (0.5%)
286 (0.4%)
0.01
Diabetes with peripheral circulatory disorders with 
ICD-10  Copy; n (%)
789 (4.7%)
773 (4.6%)
548 (2.4%)
565 (2.4%)
1,805 (6.3%)
1,788 (6.2%)
3,142 (4.6%)
3,126 (4.5%)
0.00
Diabetic Foot; n (%)
230 (1.4%)
217 (1.3%)
237 (1.0%)
258 (1.1%)
555 (1.9%)
559 (1.9%)
1,022 (1.5%)
1,034 (1.5%)
0.00
Gangrene ; n (%)
14 (0.1%)
20 (0.1%)
17 (0.1%)
5 (0.0%)
28 (0.1%)
19 (0.1%)
059 (0.1%)
044 (0.1%)
0.00
Lower extremity amputation; n (%)
40 (0.2%)
46 (0.3%)
21 (0.1%)
24 (0.1%)
87 (0.3%)
84 (0.3%)
148 (0.2%)
154 (0.2%)
0.00
Osteomyelitis; n (%)
50 (0.3%)
41 (0.2%)
56 (0.2%)
45 (0.2%)
77 (0.3%)
74 (0.3%)
183 (0.3%)
160 (0.2%)
0.02
Skin infections ; n (%)
812 (4.9%)
778 (4.6%)
925 (4.0%)
943 (4.1%)
1,598 (5.5%)
1,605 (5.6%)
3,335 (4.8%)
3,326 (4.8%)
0.00
Erectile dysfunction; n (%)
587 (3.5%)
575 (3.4%)
686 (2.9%)
655 (2.8%)
830 (2.9%)
860 (3.0%)
2,103 (3.1%)
2,090 (3.0%)
0.01
Diabetes with unspecified complication; n (%)
836 (5.0%)
814 (4.9%)
988 (4.2%)
990 (4.3%)
1,526 (5.3%)
1,517 (5.3%)
3,350 (4.9%)
3,321 (4.8%)
0.00
Diabetes mellitus without mention of complications; 
n (%)
14,237 (85.0%)
14,249 (85.1%)
21,402 (92.0%)
21,452 (92.2%)
26,407 (91.5%)
26,443 (91.7%)
62,046 (90.1%)
62,144 (90.3%)
-0.01
Hypertension: 1 inpatient or 2 outpatient claims 
within 365 days; n (%)
15,348 (91.7%)
15,341 (91.6%)
20,375 (87.6%)
20,341 (87.4%)
27,592 (95.7%)
27,624 (95.8%)
63,315 (92.0%)
63,306 (91.9%)
0.00
Hyperlipidemia ; n (%)
12,921 (77.2%)
12,951 (77.4%)
17,546 (75.4%)
17,573 (75.5%)
23,820 (82.6%)
23,824 (82.6%)
54,287 (78.8%)
54,348 (78.9%)
0.00
Edema; n (%)
721 (4.3%)
741 (4.4%)
728 (3.1%)
727 (3.1%)
2,166 (7.5%)
2,095 (7.3%)
3,615 (5.3%)
3,563 (5.2%)
0.00
Renal Dysfunction (non-diabetic) ; n (%)
1,611 (9.6%)
1,605 (9.6%)
1,291 (5.5%)
1,199 (5.2%)
3,614 (12.5%)
3,519 (12.2%)
6,516 (9.5%)
6,323 (9.2%)
0.01
Occurrence of acute renal disease ; n (%)
146 (0.9%)
135 (0.8%)
89 (0.4%)
92 (0.4%)
300 (1.0%)
320 (1.1%)
535 (0.8%)
547 (0.8%)
0.00
Occurrence of chronic renal insufficiency; n (%)
1,286 (7.7%)
1,321 (7.9%)
910 (3.9%)
861 (3.7%)
2,943 (10.2%)
2,882 (10.0%)
5,139 (7.5%)
5,064 (7.4%)
0.00
Chronic kidney disease ; n (%)
1,211 (7.2%)
1,235 (7.4%)
834 (3.6%)
743 (3.2%)
2,753 (9.5%)
2,646 (9.2%)
4,798 (7.0%)
4,624 (6.7%)
0.01
CKD Stage 3-4; n (%)
628 (3.8%)
635 (3.8%)
398 (1.7%)
370 (1.6%)
1,538 (5.3%)
1,534 (5.3%)
2,564 (3.7%)
2,539 (3.7%)
0.00
Occurrence of hypertensive nephropathy; n (%)
553 (3.3%)
537 (3.2%)
283 (1.2%)
295 (1.3%)
990 (3.4%)
1,006 (3.5%)
1,826 (2.7%)
1,838 (2.7%)
0.00
Occurrence of miscellaneous renal insufficiency ; n 
(%)
318 (1.9%)
314 (1.9%)
375 (1.6%)
368 (1.6%)
1,003 (3.5%)
1,026 (3.6%)
1,696 (2.5%)
1,708 (2.5%)
0.00
Glaucoma or cataracts ; n (%)
2,814 (16.8%)
2,806 (16.8%)
3,187 (13.7%)
3,120 (13.4%)
7,913 (27.4%)
7,842 (27.2%)
13,914 (20.2%)
13,768 (20.0%)
0.00
Cellulitis or abscess of toe; n (%)
176 (1.1%)
146 (0.9%)
129 (0.6%)
132 (0.6%)
332 (1.2%)
306 (1.1%)
637 (0.9%)
584 (0.8%)
0.01
Foot ulcer; n (%)
217 (1.3%)
205 (1.2%)
233 (1.0%)
255 (1.1%)
542 (1.9%)
556 (1.9%)
992 (1.4%)
1,016 (1.5%)
-0.01
Bladder stones; n (%)
11 (0.1%)
12 (0.1%)
24 (0.1%)
16 (0.1%)
41 (0.1%)
37 (0.1%)
076 (0.1%)
065 (0.1%)
0.00
Kidney stones; n (%)
267 (1.6%)
256 (1.5%)
428 (1.8%)
414 (1.8%)
667 (2.3%)
653 (2.3%)
1,362 (2.0%)
1,323 (1.9%)
0.01
Urinary tract infections (UTIs); n (%)
850 (5.1%)
871 (5.2%)
926 (4.0%)
923 (4.0%)
2,574 (8.9%)
2,543 (8.8%)
4,350 (6.3%)
4,337 (6.3%)
0.00
Dipstick urinalysis; n (%)
5,198 (31.1%)
5,250 (31.4%)
7,224 (31.1%)
7,104 (30.5%)
10,370 (36.0%)
10,618 (36.8%)
22,792 (33.1%)
22,972 (33.4%)
-0.01
Non-dipstick urinalysis; n (%)
7,491 (44.7%)
7,645 (45.7%)
9,491 (40.8%)
9,736 (41.8%)
13,163 (45.6%)
13,338 (46.2%)
30,145 (43.8%)
30,719 (44.6%)
-0.02
Urine function test; n (%)
275 (1.6%)
224 (1.3%)
362 (1.6%)
304 (1.3%)
893 (3.1%)
797 (2.8%)
1,530 (2.2%)
1,325 (1.9%)
0.02
Cytology; n (%)
76 (0.5%)
72 (0.4%)
136 (0.6%)
118 (0.5%)
208 (0.7%)
200 (0.7%)
420 (0.6%)
390 (0.6%)
0.00
Cystoscopy; n (%)
120 (0.7%)
107 (0.6%)
202 (0.9%)
156 (0.7%)
298 (1.0%)
292 (1.0%)
620 (0.9%)
555 (0.8%)
0.01
Other Covariates
Liver disease; n (%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
000 (0.0%)
000 (0.0%)
#DIV/0!
Osteoarthritis; n (%)
1,728 (10.3%)
1,733 (10.4%)
1,617 (7.0%)
1,622 (7.0%)
4,923 (17.1%)
4,854 (16.8%)
8,268 (12.0%)
8,209 (11.9%)
0.00
Other arthritis, arthropathies and musculoskeletal 
pain; n (%)
4,582 (27.4%)
4,572 (27.3%)
5,474 (23.5%)
5,476 (23.5%)
10,139 (35.1%)
10,202 (35.4%)
20,195 (29.3%)
20,250 (29.4%)
0.00
Dorsopathies; n (%)
3,062 (18.3%)
2,956 (17.7%)
3,524 (15.1%)
3,554 (15.3%)
6,484 (22.5%)
6,550 (22.7%)
13,070 (19.0%)
13,060 (19.0%)
0.00
Fractures; n (%)
284 (1.7%)
289 (1.7%)
333 (1.4%)
333 (1.4%)
677 (2.3%)
677 (2.3%)
1,294 (1.9%)
1,299 (1.9%)
0.00
Falls ; n (%)
318 (1.9%)
286 (1.7%)
106 (0.5%)
120 (0.5%)
630 (2.2%)
648 (2.2%)
1,054 (1.5%)
1,054 (1.5%)
0.00
Osteoporosis; n (%)
453 (2.7%)
444 (2.7%)
326 (1.4%)
303 (1.3%)
1,765 (6.1%)
1,786 (6.2%)
2,544 (3.7%)
2,533 (3.7%)
0.00
Hyperthyroidism; n (%)
121 (0.7%)
87 (0.5%)
117 (0.5%)
97 (0.4%)
251 (0.9%)
242 (0.8%)
489 (0.7%)
426 (0.6%)
0.01
Hypothyroidism ; n (%)
2,426 (14.5%)
2,438 (14.6%)
2,825 (12.1%)
2,723 (11.7%)
3,638 (12.6%)
3,615 (12.5%)
8,889 (12.9%)
8,776 (12.7%)
0.01
Other disorders of thyroid gland ; n (%)
664 (4.0%)
631 (3.8%)
840 (3.6%)
824 (3.5%)
1,287 (4.5%)
1,291 (4.5%)
2,791 (4.1%)
2,746 (4.0%)
0.01
Depression; n (%)
1,229 (7.3%)
1,217 (7.3%)
1,471 (6.3%)
1,423 (6.1%)
2,574 (8.9%)
2,543 (8.8%)
5,274 (7.7%)
5,183 (7.5%)
0.01
Anxiety; n (%)
1,167 (7.0%)
1,136 (6.8%)
1,084 (4.7%)
1,088 (4.7%)
2,123 (7.4%)
2,036 (7.1%)
4,374 (6.4%)
4,260 (6.2%)
0.01
Sleep_Disorder; n (%)
1,227 (7.3%)
1,260 (7.5%)
2,580 (11.1%)
2,582 (11.1%)
2,379 (8.2%)
2,430 (8.4%)
6,186 (9.0%)
6,272 (9.1%)
0.00
Dementia; n (%)
155 (0.9%)
162 (1.0%)
112 (0.5%)
120 (0.5%)
902 (3.1%)
938 (3.3%)
1,169 (1.7%)
1,220 (1.8%)
-0.01
Delirium; n (%)
39 (0.2%)
46 (0.3%)
36 (0.2%)
35 (0.2%)
179 (0.6%)
186 (0.6%)
254 (0.4%)
267 (0.4%)
0.00
Psychosis; n (%)
65 (0.4%)
77 (0.5%)
32 (0.1%)
44 (0.2%)
223 (0.8%)
257 (0.9%)
320 (0.5%)
378 (0.5%)
0.00
Obesity; n (%)
4,419 (26.4%)
4,456 (26.6%)
4,267 (18.3%)
4,308 (18.5%)
5,666 (19.6%)
5,680 (19.7%)
14,352 (20.8%)
14,444 (21.0%)
0.00
Overweight; n (%)
838 (5.0%)
841 (5.0%)
537 (2.3%)
530 (2.3%)
1,065 (3.7%)
1,063 (3.7%)
2,440 (3.5%)
2,434 (3.5%)
0.00
Smoking; n (%)
1,399 (8.4%)
1,383 (8.3%)
1,206 (5.2%)
1,169 (5.0%)
3,129 (10.8%)
3,165 (11.0%)
5,734 (8.3%)
5,717 (8.3%)
0.00
Alcohol abuse or dependence; n (%)
5 (0.0%)
0 (0.0%)
7 (0.0%)
6 (0.0%)
**
**
**
**
**
Drug abuse or dependence; n (%)
3 (0.0%)
7 (0.0%)
4 (0.0%)
4 (0.0%)
**
**
**
**
**
COPD; n (%)
851 (5.1%)
834 (5.0%)
633 (2.7%)
643 (2.8%)
2,322 (8.0%)
2,360 (8.2%)
3,806 (5.5%)
3,837 (5.6%)
0.00
Table 1

Asthma; n (%)
846 (5.1%)
794 (4.7%)
817 (3.5%)
834 (3.6%)
1,494 (5.2%)
1,542 (5.3%)
3,157 (4.6%)
3,170 (4.6%)
0.00
Obstructive sleep apnea; n (%)
1,899 (11.3%)
1,960 (11.7%)
2,788 (12.0%)
2,804 (12.1%)
2,661 (9.2%)
2,680 (9.3%)
7,348 (10.7%)
7,444 (10.8%)
0.00
Pneumonia; n (%)
181 (1.1%)
190 (1.1%)
187 (0.8%)
208 (0.9%)
471 (1.6%)
474 (1.6%)
839 (1.2%)
872 (1.3%)
-0.01
Imaging; n (%)
2 (0.0%)
3 (0.0%)
3 (0.0%)
3 (0.0%)
15 (0.1%)
12 (0.0%)
20 (0.0%)
18 (0.0%)
#DIV/0!
Diabetes Medications
DM Medications - AGIs; n (%)
61 (0.4%)
63 (0.4%)
72 (0.3%)
73 (0.3%)
180 (0.6%)
197 (0.7%)
313 (0.5%)
333 (0.5%)
0.00
DM Medications - Glitazones; n (%)
1,570 (9.4%)
1,478 (8.8%)
2,106 (9.1%)
2,058 (8.8%)
2,732 (9.5%)
2,715 (9.4%)
6,408 (9.3%)
6,251 (9.1%)
0.01
DM Medications - Insulin; n (%)
4,643 (27.7%)
4,731 (28.3%)
6,185 (26.6%)
6,447 (27.7%)
9,686 (33.6%)
9,923 (34.4%)
20,514 (29.8%)
21,101 (30.6%)
-0.02
DM Medications - Meglitinides; n (%)
227 (1.4%)
223 (1.3%)
418 (1.8%)
421 (1.8%)
744 (2.6%)
791 (2.7%)
1,389 (2.0%)
1,435 (2.1%)
-0.01
DM Medications - Metformin; n (%)
13,035 (77.9%)
13,035 (77.9%)
18,359 (78.9%)
18,245 (78.4%)
21,390 (74.2%)
21,384 (74.1%)
52,784 (76.7%)
52,664 (76.5%)
0.00
Concomitant initiation or current use of DPP4i Copy; 
n (%)
3,291 (19.7%)
3,255 (19.4%)
5,946 (25.6%)
5,704 (24.5%)
7,563 (26.2%)
7,384 (25.6%)
16,800 (24.4%)
16,343 (23.7%)
0.02
Concomitant initiation or current use of AGIs; n (%)
40 (0.2%)
45 (0.3%)
44 (0.2%)
36 (0.2%)
124 (0.4%)
139 (0.5%)
208 (0.3%)
220 (0.3%)
0.00
Concomitant initiation or current use of Glitazones; 
n (%)
1,230 (7.3%)
1,133 (6.8%)
1,583 (6.8%)
1,544 (6.6%)
2,061 (7.1%)
2,060 (7.1%)
4,874 (7.1%)
4,737 (6.9%)
0.01
Concomitant initiation or current use of GLP-1 RA; n 
(%)
1,791 (10.7%)
1,857 (11.1%)
2,706 (11.6%)
2,734 (11.8%)
2,458 (8.5%)
2,727 (9.5%)
6,955 (10.1%)
7,318 (10.6%)
-0.02
Concomitant initiation or current use of Insulin; n 
(%)
3,487 (20.8%)
3,579 (21.4%)
4,765 (20.5%)
4,982 (21.4%)
7,619 (26.4%)
7,943 (27.5%)
15,871 (23.1%)
16,504 (24.0%)
-0.02
Concomitant initiation or current use of 
Meglitinides; n (%)
130 (0.8%)
155 (0.9%)
241 (1.0%)
289 (1.2%)
526 (1.8%)
563 (2.0%)
897 (1.3%)
1,007 (1.5%)
-0.02
Concomitant initiation or current use of Metformin; 
n (%)
10,980 (65.6%)
10,982 (65.6%)
15,378 (66.1%)
15,321 (65.9%)
18,049 (62.6%)
18,065 (62.6%)
44,407 (64.5%)
44,368 (64.4%)
0.00
Past use of DPP4i Copy; n (%)
1,151 (6.9%)
1,121 (6.7%)
1,783 (7.7%)
1,697 (7.3%)
2,213 (7.7%)
2,127 (7.4%)
5,147 (7.5%)
4,945 (7.2%)
0.01
Past use of AGIs Copy; n (%)
21 (0.1%)
18 (0.1%)
28 (0.1%)
37 (0.2%)
56 (0.2%)
58 (0.2%)
105 (0.2%)
113 (0.2%)
0.00
Past use of Glitazones Copy; n (%)
340 (2.0%)
345 (2.1%)
523 (2.2%)
514 (2.2%)
671 (2.3%)
655 (2.3%)
1,534 (2.2%)
1,514 (2.2%)
0.00
Past use of GLP-1 RA Copy; n (%)
823 (4.9%)
826 (4.9%)
1,206 (5.2%)
1,219 (5.2%)
1,172 (4.1%)
1,224 (4.2%)
3,201 (4.6%)
3,269 (4.7%)
0.00
Past use of Insulin Copy; n (%)
1,156 (6.9%)
1,152 (6.9%)
1,420 (6.1%)
1,465 (6.3%)
2,067 (7.2%)
1,981 (6.9%)
4,643 (6.7%)
4,598 (6.7%)
0.00
Past use of Meglitinides Copy; n (%)
97 (0.6%)
68 (0.4%)
177 (0.8%)
132 (0.6%)
218 (0.8%)
228 (0.8%)
492 (0.7%)
428 (0.6%)
0.01
Past use of metformin (final) Copy; n (%)
2,055 (12.3%)
2,053 (12.3%)
2,981 (12.8%)
2,924 (12.6%)
3,341 (11.6%)
3,319 (11.5%)
8,377 (12.2%)
8,296 (12.0%)
0.01
Other Medications
Use of ACE inhibitors; n (%)
8,762 (52.3%)
8,727 (52.1%)
11,715 (50.4%)
11,848 (50.9%)
13,662 (47.4%)
13,602 (47.2%)
34,139 (49.6%)
34,177 (49.6%)
0.00
Use of ARBs; n (%)
6,316 (37.7%)
6,365 (38.0%)
9,235 (39.7%)
9,169 (39.4%)
11,406 (39.5%)
11,415 (39.6%)
26,957 (39.2%)
26,949 (39.1%)
0.00
Use of Loop Diuretics ; n (%)
1,436 (8.6%)
1,463 (8.7%)
1,706 (7.3%)
1,750 (7.5%)
4,396 (15.2%)
4,395 (15.2%)
7,538 (10.9%)
7,608 (11.1%)
-0.01
Use of other diuretics; n (%)
460 (2.7%)
456 (2.7%)
595 (2.6%)
579 (2.5%)
975 (3.4%)
981 (3.4%)
2,030 (2.9%)
2,016 (2.9%)
0.00
Use of nitrates-United; n (%)
570 (3.4%)
543 (3.2%)
673 (2.9%)
696 (3.0%)
1,759 (6.1%)
1,776 (6.2%)
3,002 (4.4%)
3,015 (4.4%)
0.00
Use of other hypertension drugs; n (%)
836 (5.0%)
841 (5.0%)
1,023 (4.4%)
1,042 (4.5%)
2,103 (7.3%)
2,069 (7.2%)
3,962 (5.8%)
3,952 (5.7%)
0.00
Use of digoxin; n (%)
160 (1.0%)
175 (1.0%)
214 (0.9%)
221 (0.9%)
654 (2.3%)
606 (2.1%)
1,028 (1.5%)
1,002 (1.5%)
0.00
Use of Anti-arrhythmics; n (%)
147 (0.9%)
146 (0.9%)
189 (0.8%)
190 (0.8%)
433 (1.5%)
440 (1.5%)
769 (1.1%)
776 (1.1%)
0.00
Use of COPD/asthma meds; n (%)
2,395 (14.3%)
2,326 (13.9%)
3,399 (14.6%)
3,371 (14.5%)
4,932 (17.1%)
4,962 (17.2%)
10,726 (15.6%)
10,659 (15.5%)
0.00
Use of statins; n (%)
12,032 (71.9%)
12,150 (72.6%)
16,087 (69.1%)
16,153 (69.4%)
21,847 (75.7%)
21,876 (75.8%)
49,966 (72.6%)
50,179 (72.9%)
-0.01
Use of other lipid-lowering drugs; n (%)
2,203 (13.2%)
2,259 (13.5%)
3,621 (15.6%)
3,669 (15.8%)
4,378 (15.2%)
4,409 (15.3%)
10,202 (14.8%)
10,337 (15.0%)
-0.01
Use of antiplatelet agents; n (%)
1,646 (9.8%)
1,642 (9.8%)
2,383 (10.2%)
2,401 (10.3%)
4,209 (14.6%)
4,265 (14.8%)
8,238 (12.0%)
8,308 (12.1%)
0.00
Use of oral anticoagulants (Dabigatran, Rivaroxaban, 
Apixaban, Warfarin); n (%)
711 (4.2%)
713 (4.3%)
774 (3.3%)
785 (3.4%)
2,191 (7.6%)
2,225 (7.7%)
3,676 (5.3%)
3,723 (5.4%)
0.00
Use of heparin and other low-molecular weight 
heparins; n (%)
17 (0.1%)
16 (0.1%)
0 (0.0%)
0 (0.0%)
63 (0.2%)
69 (0.2%)
080 (0.1%)
085 (0.1%)
0.00
Use of NSAIDs; n (%)
2,804 (16.8%)
2,766 (16.5%)
3,777 (16.2%)
3,810 (16.4%)
4,635 (16.1%)
4,674 (16.2%)
11,216 (16.3%)
11,250 (16.3%)
0.00
Use of oral corticosteroids; n (%)
2,110 (12.6%)
2,010 (12.0%)
2,618 (11.3%)
2,588 (11.1%)
4,136 (14.3%)
4,125 (14.3%)
8,864 (12.9%)
8,723 (12.7%)
0.01
Use of bisphosphonate (United); n (%)
209 (1.2%)
202 (1.2%)
164 (0.7%)
155 (0.7%)
811 (2.8%)
819 (2.8%)
1,184 (1.7%)
1,176 (1.7%)
0.00
Use of opioids; n (%)
3,250 (19.4%)
3,204 (19.1%)
4,506 (19.4%)
4,557 (19.6%)
5,860 (20.3%)
5,864 (20.3%)
13,616 (19.8%)
13,625 (19.8%)
0.00
Use of antidepressants; n (%)
3,994 (23.9%)
3,963 (23.7%)
5,150 (22.1%)
5,158 (22.2%)
7,507 (26.0%)
7,437 (25.8%)
16,651 (24.2%)
16,558 (24.0%)
0.00
Use of antipsychotics; n (%)
300 (1.8%)
303 (1.8%)
281 (1.2%)
287 (1.2%)
678 (2.4%)
701 (2.4%)
1,259 (1.8%)
1,291 (1.9%)
-0.01
Use of anticonvulsants; n (%)
2,436 (14.6%)
2,322 (13.9%)
2,448 (10.5%)
2,480 (10.7%)
4,502 (15.6%)
4,524 (15.7%)
9,386 (13.6%)
9,326 (13.5%)
0.00
Use of lithium; n (%)
15 (0.1%)
20 (0.1%)
33 (0.1%)
11 (0.0%)
38 (0.1%)
27 (0.1%)
086 (0.1%)
058 (0.1%)
0.00
Use of Benzos; n (%)
1,504 (9.0%)
1,501 (9.0%)
1,957 (8.4%)
1,972 (8.5%)
2,903 (10.1%)
2,856 (9.9%)
6,364 (9.2%)
6,329 (9.2%)
0.00
Use of anxiolytics/hypnotics; n (%)
932 (5.6%)
906 (5.4%)
1,304 (5.6%)
1,324 (5.7%)
1,707 (5.9%)
1,632 (5.7%)
3,943 (5.7%)
3,862 (5.6%)
0.00
Use of dementia meds; n (%)
104 (0.6%)
112 (0.7%)
82 (0.4%)
88 (0.4%)
760 (2.6%)
785 (2.7%)
946 (1.4%)
985 (1.4%)
0.00
Use of antiparkinsonian meds; n (%)
322 (1.9%)
325 (1.9%)
374 (1.6%)
362 (1.6%)
830 (2.9%)
852 (3.0%)
1,526 (2.2%)
1,539 (2.2%)
0.00
Any use of pramlintide; n (%)
0 (0.0%)
28 (0.2%)
10 (0.0%)
41 (0.2%)
**
**
**
**
**
Any use of 1st generation sulfonylureas; n (%)
1 (0.0%)
2 (0.0%)
6 (0.0%)
1 (0.0%)
**
**
**
**
**
Entresto (sacubitril/valsartan); n (%)
15 (0.1%)
8 (0.0%)
10 (0.0%)
6 (0.0%)
**
**
**
**
**
Initiation as monotherapy  Copy; n (%)
1,194 (7.1%)
1,198 (7.2%)
1,283 (5.5%)
1,306 (5.6%)
1,205 (4.2%)
1,233 (4.3%)
3,682 (5.3%)
3,737 (5.4%)
0.00
Labs
                                          40,005                                           40,005 
Lab values- HbA1c (%) ; n (%)
7,105 (42.4%)
7,211 (43.1%)
1,740 (7.5%)
1,440 (6.2%)
N/A
N/A
8,845 (22.1%)
8,651 (21.6%)
0.01
Lab values- HbA1c (%) (within 3 months) ; n (%)
5,645 (33.7%)
5,910 (35.3%)
1,376 (5.9%)
1,224 (5.3%)
N/A
N/A
7,021 (17.6%)
7,134 (17.8%)
-0.01
Lab values- HbA1c (%) (within 6 months) ; n (%)
7,105 (42.4%)
7,211 (43.1%)
1,740 (7.5%)
1,440 (6.2%)
N/A
N/A
8,845 (22.1%)
8,651 (21.6%)
0.01
Table 1

Lab values- BNP; n (%)
73 (0.4%)
99 (0.6%)
14 (0.1%)
13 (0.1%)
N/A
N/A
087 (0.2%)
112 (0.3%)
-0.02
Lab values- BNP (within 3 months); n (%)
42 (0.3%)
64 (0.4%)
8 (0.0%)
9 (0.0%)
N/A
N/A
050 (0.1%)
073 (0.2%)
-0.03
Lab values- BNP (within 6 months); n (%)
73 (0.4%)
99 (0.6%)
14 (0.1%)
13 (0.1%)
N/A
N/A
087 (0.2%)
112 (0.3%)
-0.02
Lab values- BUN (mg/dl); n (%)
6,923 (41.4%)
7,113 (42.5%)
1,610 (6.9%)
1,347 (5.8%)
N/A
N/A
8,533 (21.3%)
8,460 (21.1%)
0.00
Lab values- BUN (mg/dl) (within 3 months); n (%)
5,349 (32.0%)
5,668 (33.9%)
1,229 (5.3%)
1,095 (4.7%)
N/A
N/A
6,578 (16.4%)
6,763 (16.9%)
-0.01
Lab values- BUN (mg/dl) (within 6 months); n (%)
6,923 (41.4%)
7,113 (42.5%)
1,610 (6.9%)
1,347 (5.8%)
N/A
N/A
8,533 (21.3%)
8,460 (21.1%)
0.00
Lab values- Creatinine (mg/dl) ; n (%)
7,103 (42.4%)
7,370 (44.0%)
1,719 (7.4%)
1,488 (6.4%)
N/A
N/A
8,822 (22.1%)
8,858 (22.1%)
0.00
Lab values- Creatinine (mg/dl) (within 3 months) ; n 
(%)
5,484 (32.8%)
5,872 (35.1%)
1,321 (5.7%)
1,221 (5.2%)
N/A
N/A
6,805 (17.0%)
7,093 (17.7%)
-0.02
Lab values- Creatinine (mg/dl) (within 6 months) ; n 
(%)
7,103 (42.4%)
7,370 (44.0%)
1,719 (7.4%)
1,488 (6.4%)
N/A
N/A
8,822 (22.1%)
8,858 (22.1%)
0.00
Lab values- HDL level (mg/dl); n (%)
6,063 (36.2%)
6,278 (37.5%)
1,611 (6.9%)
1,358 (5.8%)
N/A
N/A
7,674 (19.2%)
7,636 (19.1%)
0.00
Lab values- HDL level (mg/dl) (within 3 months); n (%)
4,499 (26.9%)
4,780 (28.6%)
1,182 (5.1%)
1,058 (4.5%)
N/A
N/A
5,681 (14.2%)
5,838 (14.6%)
-0.01
Lab values- HDL level (mg/dl) (within 6 months); n (%)
6,063 (36.2%)
6,278 (37.5%)
1,611 (6.9%)
1,358 (5.8%)
N/A
N/A
7,674 (19.2%)
7,636 (19.1%)
0.00
Lab values- LDL level (mg/dl) ; n (%)
6,280 (37.5%)
6,482 (38.7%)
1,663 (7.1%)
1,379 (5.9%)
N/A
N/A
7,943 (19.9%)
7,861 (19.7%)
0.01
Lab values- LDL level (mg/dl) (within 3 months) ; n (%)
4,650 (27.8%)
4,954 (29.6%)
1,216 (5.2%)
1,078 (4.6%)
N/A
N/A
5,866 (14.7%)
6,032 (15.1%)
-0.01
Lab values- LDL level (mg/dl) (within 6 months) ; n (%)
6,280 (37.5%)
6,482 (38.7%)
1,663 (7.1%)
1,379 (5.9%)
N/A
N/A
7,943 (19.9%)
7,861 (19.7%)
0.01
Lab values- NT-proBNP; n (%)
13 (0.1%)
9 (0.1%)
4 (0.0%)
0 (0.0%)
N/A
N/A
17 (0.0%)
0 (0.0%)
-
Lab values- NT-proBNP (within 3 months); n (%)
9 (0.1%)
5 (0.0%)
2 (0.0%)
0 (0.0%)
N/A
N/A
11 (0.0%)
0 (0.0%)
-
Lab values- NT-proBNP (within 6 months); n (%)
13 (0.1%)
9 (0.1%)
4 (0.0%)
0 (0.0%)
N/A
N/A
17 (0.0%)
9 (0.0%)
-
Lab values- Total cholesterol (mg/dl) ; n (%)
6,193 (37.0%)
6,409 (38.3%)
1,610 (6.9%)
1,363 (5.9%)
N/A
N/A
7,803 (19.5%)
7,772 (19.4%)
0.00
Lab values- Total cholesterol (mg/dl) (within 3 
months) ; n (%)
4,591 (27.4%)
4,894 (29.2%)
1,183 (5.1%)
1,066 (4.6%)
N/A
N/A
5,774 (14.4%)
5,960 (14.9%)
-0.01
Lab values- Total cholesterol (mg/dl) (within 6 
months) ; n (%)
6,193 (37.0%)
6,409 (38.3%)
1,610 (6.9%)
1,363 (5.9%)
N/A
N/A
7,803 (19.5%)
7,772 (19.4%)
0.00
Lab values- Triglyceride level (mg/dl); n (%)
6,139 (36.7%)
6,366 (38.0%)
1,598 (6.9%)
1,343 (5.8%)
N/A
N/A
7,737 (19.3%)
7,709 (19.3%)
0.00
Lab values- Triglyceride level (mg/dl) (within 3 
months); n (%)
4,554 (27.2%)
4,857 (29.0%)
1,177 (5.1%)
1,053 (4.5%)
N/A
N/A
5,731 (14.3%)
5,910 (14.8%)
-0.01
Lab values- Triglyceride level (mg/dl) (within 6 
months); n (%)
6,139 (36.7%)
6,366 (38.0%)
1,598 (6.9%)
1,343 (5.8%)
N/A
N/A
7,737 (19.3%)
7,709 (19.3%)
0.00
Lab result number- HbA1c (%) mean (only 2 to 20 
included) 
7,067
                                            
7,168
                                            
1,685
                                            
1,391
                                            
N/A
N/A                                              8,752                                              8,559 
...mean (sd)
8.55 (1.87)
8.50 (1.76)
8.59 (1.89)
8.53 (1.77)
N/A
N/A
8.56 (1.87)
8.50 (1.76)
0.03
...median [IQR]
8.10 [7.20, 9.60]
8.10 [7.25, 9.43]
8.10 [7.30, 9.50]
8.10 [7.25, 9.40]
N/A
N/A
8.10 (1.87)
8.10 (1.76)
0.00
...Missing; n (%)
9,673 (57.8%)
9,572 (57.2%)
21,580 (92.8%)
21,874 (94.0%)
N/A
N/A
31,253 (78.1%)
31,446 (78.6%)
-0.01
Lab result number- BNP mean 
73
                                                   
99
                                                   
14
                                                   
13
                                                   
N/A
N/A                                                     87                                                  112 
...mean (sd)
105.60 (266.26)
68.61 (79.50)
110.61 (177.08)
575.59 (1,341.91)
N/A
N/A
106.41 (256.16)
127.46 (451.58)
-0.06
...median [IQR]
43.00 [18.05, 97.15]
40.40 [17.00, 86.10]
45.00 [17.75, 119.62]
56.00 [20.00, 194.30]
N/A
N/A
#VALUE!
#VALUE!
#VALUE!
...Missing; n (%)
16,667 (99.6%)
16,641 (99.4%)
23,251 (99.9%)
23,252 (99.9%)
N/A
N/A
39,918 (99.8%)
39,893 (99.7%)
0.02
Lab result number- BUN (mg/dl) mean 
                                             6,923                                              7,113                                              1,610                                              1,347 
N/A
N/A                                              8,533                                              8,460 
...mean (sd)
16.86 (6.32)
16.65 (5.62)
988.41 (11,243.54)
2,413.80 (18,907.89)
N/A
N/A
200.17 (4883.23)
398.32 (7543.23)
-0.03
...median [IQR]
16.00 [13.00, 19.50]
16.00 [13.00, 19.00]
15.83 [13.00, 19.00]
16.00 [13.00, 19.00]
N/A
N/A
#VALUE!
#VALUE!
#VALUE!
...Missing; n (%)
9,817 (58.6%)
9,627 (57.5%)
21,655 (93.1%)
21,918 (94.2%)
N/A
N/A
31,472 (78.7%)
31,545 (78.9%)
0.00
Lab result number- Creatinine (mg/dl) mean (only 0.1 
to 15 included) 
                                             7,065                                              7,319                                              1,572                                              1,354 
N/A
N/A                                              8,637                                              8,673 
...mean (sd)
0.95 (0.29)
0.92 (0.24)
0.95 (0.28)
0.92 (0.23)
N/A
N/A
0.95 (0.29)
0.92 (0.24)
0.11
...median [IQR]
0.90 [0.76, 1.07]
0.89 [0.76, 1.04]
0.91 [0.76, 1.06]
0.89 [0.76, 1.05]
N/A
N/A
0.90 (0.29)
0.89 (0.24)
0.04
...Missing; n (%)
9,675 (57.8%)
9,421 (56.3%)
21,693 (93.2%)
21,911 (94.2%)
N/A
N/A
31,368 (78.4%)
31,332 (78.3%)
0.00
Lab result number- HDL level (mg/dl) mean (only 
=<5000 included) 
                                             6,063                                              6,278                                              1,600                                              1,341 
N/A
N/A                                              7,663                                              7,619 
...mean (sd)
44.91 (13.29)
45.34 (13.17)
44.01 (13.95)
46.54 (108.97)
N/A
N/A
44.72 (13.43)
45.55 (47.25)
-0.02
...median [IQR]
43.00 [36.00, 52.00]
43.50 [36.28, 52.00]
43.00 [36.00, 51.00]
43.00 [35.00, 50.75]
N/A
N/A
43.00 (13.43)
43.41 (47.25)
-0.01
...Missing; n (%)
10,677 (63.8%)
10,462 (62.5%)
21,665 (93.1%)
21,924 (94.2%)
N/A
N/A
32,342 (80.8%)
32,386 (81.0%)
-0.01
Lab result number- LDL level (mg/dl) mean (only 
=<5000 included) 
                                             6,127                                              6,357                                              1,464                                              1,218 
N/A
N/A                                              7,591                                              7,575 
...mean (sd)
85.82 (40.64)
84.61 (39.33)
89.35 (41.61)
86.98 (40.52)
N/A
N/A
86.50 (40.83)
84.99 (39.53)
0.04
...median [IQR]
84.00 [62.00, 109.00]
82.00 [61.00, 107.00]
88.25 [65.00, 113.50]
85.88 [63.00, 112.00]
N/A
N/A
84.82 (40.83)
82.62 (39.53)
0.05
...Missing; n (%)
10,613 (63.4%)
10,383 (62.0%)
21,801 (93.7%)
22,047 (94.8%)
N/A
N/A
32,414 (81.0%)
32,430 (81.1%)
0.00
Lab result number- Total cholesterol (mg/dl) mean 
(only =<5000 included) 
                                             6,190                                              6,403                                              1,597                                              1,344 
N/A
N/A                                              7,787                                              7,747 
...mean (sd)
174.42 (47.37)
172.68 (46.78)
175.05 (50.49)
172.22 (55.71)
N/A
N/A
174.55 (48.03)
172.60 (48.45)
0.04
...median [IQR]
169.00 [143.00, 199.00]
167.00 [142.00, 196.00]
171.00 [145.00, 202.00]
170.00 [144.50, 197.00]
N/A
N/A
169.41 (48.03)
167.52 (48.45)
0.04
...Missing; n (%)
10,550 (63.0%)
10,337 (61.8%)
21,668 (93.1%)
21,921 (94.2%)
N/A
N/A
32,218 (80.5%)
32,258 (80.6%)
0.00
Table 1

Lab result number- Triglyceride level (mg/dl) mean 
(only =<5000 included) 
                                             6,138                                              6,365                                              1,585                                              1,324 
N/A
N/A                                              7,723                                              7,689 
...mean (sd)
199.03 (170.61)
197.06 (178.97)
193.72 (167.75)
195.36 (188.68)
N/A
N/A
197.94 (170.04)
196.77 (180.69)
0.01
...median [IQR]
159.00 [111.00, 231.00]
157.33 [112.00, 226.00]
155.00 [109.00, 223.75]
160.00 [112.00, 227.00]
N/A
N/A
158.18 (170.04)
157.79 (180.69)
0.00
...Missing; n (%)
10,602 (63.3%)
10,375 (62.0%)
21,680 (93.2%)
21,941 (94.3%)
N/A
N/A
32,282 (80.7%)
32,316 (80.8%)
0.00
Lab result number- Hemoglobin mean (only >0 
included)
                                             4,465                                              4,725                                              1,110                                                  856 
N/A
N/A                                              5,575                                              5,581 
...mean (sd)
13.82 (1.54)
14.06 (1.56)
10,214.28 (300,385.23)
14,006.95 (342,165.79)
N/A
N/A
2044.76 (134010.49)
2160.25 (133961.62)
0.00
...median [IQR]
13.83 [12.80, 14.80]
14.10 [13.00, 15.10]
13.80 [12.80, 14.70]
14.00 [12.90, 15.00]
N/A
N/A
#VALUE!
#VALUE!
#VALUE!
...Missing; n (%)
12,275 (73.3%)
12,015 (71.8%)
22,155 (95.2%)
22,409 (96.3%)
N/A
N/A
34,430 (86.1%)
34,424 (86.0%)
0.00
Lab result number- Serum sodium mean (only > 90 
and < 190 included)
                                             6,917                                              7,194                                              1,610                                              1,327 
N/A
N/A                                              8,527                                              8,521 
...mean (sd)
139.22 (2.73)
139.28 (2.62)
138.81 (2.80)
139.05 (2.41)
N/A
N/A
139.14 (2.74)
139.24 (2.59)
-0.04
...median [IQR]
139.00 [137.67, 141.00]
139.00 [138.00, 141.00]
139.00 [137.00, 140.50]
139.00 [138.00, 140.67]
N/A
N/A
139.00 (2.74)
139.00 (2.59)
0.00
...Missing; n (%)
9,823 (58.7%)
9,546 (57.0%)
21,655 (93.1%)
21,938 (94.3%)
N/A
N/A
31,478 (78.7%)
31,484 (78.7%)
0.00
Lab result number- Albumin mean (only >0 and <=10 
included)
                                             6,438                                              6,794                                              1,399                                              1,117 
N/A
N/A                                              7,837                                              7,911 
...mean (sd)
4.29 (0.30)
4.30 (0.30)
4.19 (0.62)
4.16 (0.70)
N/A
N/A
4.27 (0.38)
4.28 (0.38)
-0.03
...median [IQR]
4.30 [4.10, 4.50]
4.30 [4.10, 4.50]
4.30 [4.00, 4.50]
4.30 [4.00, 4.50]
N/A
N/A
4.30 (0.38)
4.30 (0.38)
0.00
...Missing; n (%)
10,302 (61.5%)
9,946 (59.4%)
21,866 (94.0%)
22,148 (95.2%)
N/A
N/A
32,168 (80.4%)
32,094 (80.2%)
0.01
Lab result number- Glucose (fasting or random) mean 
(only 10-1000 included)
                                             6,905                                              7,185                                              1,588                                              1,309 
N/A
N/A                                              8,493                                              8,494 
...mean (sd)
182.23 (74.88)
178.16 (69.58)
182.28 (74.67)
176.56 (63.34)
N/A
N/A
182.24 (74.85)
177.91 (68.66)
0.06
...median [IQR]
164.00 [130.45, 217.00]
162.00 [130.00, 211.00]
164.25 [131.00, 214.75]
163.00 [132.00, 209.00]
N/A
N/A
164.05 (74.85)
162.15 (68.66)
0.03
...Missing; n (%)
9,835 (58.8%)
9,555 (57.1%)
21,677 (93.2%)
21,956 (94.4%)
N/A
N/A
31,512 (78.8%)
31,511 (78.8%)
0.00
Lab result number- Potassium mean (only 1-7 
included)
                                             7,074                                              7,329                                              1,561                                              1,293 
N/A
N/A                                              8,635                                              8,622 
...mean (sd)
4.45 (0.40)
4.44 (0.40)
4.37 (0.43)
4.36 (0.41)
N/A
N/A
4.44 (0.41)
4.43 (0.40)
0.02
...median [IQR]
4.40 [4.20, 4.70]
4.40 [4.20, 4.70]
4.35 [4.05, 4.60]
4.35 [4.10, 4.60]
N/A
N/A
4.39 (0.41)
4.39 (0.40)
0.00
...Missing; n (%)
9,666 (57.7%)
9,411 (56.2%)
21,704 (93.3%)
21,972 (94.4%)
N/A
N/A
31,370 (78.4%)
31,383 (78.4%)
0.00
Comorbidity Scores
CCI (180 days)- ICD9 and ICD10 
...mean (sd)
2.07 (1.27)
2.07 (1.28)
1.65 (0.99)
1.65 (0.98)
2.36 (1.50)
2.37 (1.51)
2.05 (1.29)
2.05 (1.30)
0.00
...median [IQR]
2.00 [1.00, 2.00]
2.00 [1.00, 2.00]
1.00 [1.00, 2.00]
1.00 [1.00, 2.00]
2.00 [1.00, 3.00]
2.00 [1.00, 3.00]
1.66 (1.29)
1.66 (1.30)
0.00
Frailty Score: Qualitative Version 365 days as 
Categories, 
...0; n (%)
10,978 (65.6%)
10,837 (64.7%)
12,728 (54.7%)
12,498 (53.7%)
13,174 (45.7%)
13,018 (45.1%)
36,880 (53.6%)
36,353 (52.8%)
0.02
...1 to 2; n (%)
4,527 (27.0%)
4,585 (27.4%)
8,508 (36.6%)
8,680 (37.3%)
10,071 (34.9%)
10,062 (34.9%)
23,106 (33.6%)
23,327 (33.9%)
-0.01
...3 or more; n (%)
1,235 (7.4%)
1,318 (7.9%)
2,029 (8.7%)
2,087 (9.0%)
5,600 (19.4%)
5,765 (20.0%)
8,864 (12.9%)
9,170 (13.3%)
-0.01
Frailty Score: Empirical Version 365 days as 
Categories, 
...< 0.12908; n (%)
5,736 (34.3%)
5,863 (35.0%)
7,903 (34.0%)
7,780 (33.4%)
4,472 (15.5%)
4,654 (16.1%)
18,111 (26.3%)
18,297 (26.6%)
-0.01
...0.12908 - 0.1631167; n (%)
6,275 (37.5%)
6,241 (37.3%)
9,182 (39.5%)
9,210 (39.6%)
9,121 (31.6%)
8,892 (30.8%)
24,578 (35.7%)
24,343 (35.4%)
0.01
...>= 0.1631167; n (%)
4,729 (28.2%)
4,636 (27.7%)
6,180 (26.6%)
6,275 (27.0%)
15,252 (52.9%)
15,299 (53.0%)
26,161 (38.0%)
26,210 (38.1%)
0.00
Non-Frailty; n (%)
9,549 (57.0%)
9,735 (58.2%)
12,416 (53.4%)
12,489 (53.7%)
1,626 (5.6%)
1,331 (4.6%)
23,591 (34.3%)
23,555 (34.2%)
0.00
Frailty Score (mean): Qualitative Version 365 days, 
...mean (sd)
0.64 (1.16)
0.67 (1.20)
0.81 (1.19)
0.83 (1.20)
1.29 (1.69)
1.31 (1.69)
0.97 (1.42)
0.99 (1.43)
-0.01
...median [IQR]
0.00 [0.00, 1.00]
0.00 [0.00, 1.00]
0.00 [0.00, 1.00]
0.00 [0.00, 1.00]
1.00 [0.00, 2.00]
1.00 [0.00, 2.00]
0.42 (1.42)
0.42 (1.43)
0.00
Frailty Score (mean): Empirical Version 365 days, 
...mean (sd)
0.15 (0.04)
0.15 (0.04)
0.14 (0.04)
0.14 (0.04)
0.18 (0.05)
0.18 (0.05)
0.16 (0.04)
0.16 (0.04)
0.00
...median [IQR]
0.14 [0.12, 0.17]
0.14 [0.12, 0.17]
0.14 [0.12, 0.16]
0.14 [0.12, 0.16]
0.17 [0.14, 0.20]
0.17 [0.14, 0.20]
0.15 (0.04)
0.15 (0.04)
0.00
Healthcare Utilization
Any hospitalization; n (%)
422 (2.5%)
395 (2.4%)
472 (2.0%)
486 (2.1%)
1,130 (3.9%)
1,123 (3.9%)
2,024 (2.9%)
2,004 (2.9%)
0.00
Any hospitalization within prior 30 days; n (%)
73 (0.4%)
63 (0.4%)
66 (0.3%)
77 (0.3%)
166 (0.6%)
186 (0.6%)
305 (0.4%)
326 (0.5%)
-0.01
Any hospitalization during prior 31-180 days; n (%)
352 (2.1%)
333 (2.0%)
411 (1.8%)
413 (1.8%)
985 (3.4%)
959 (3.3%)
1,748 (2.5%)
1,705 (2.5%)
0.00
Endocrinologist Visit; n (%)
2,703 (16.1%)
2,677 (16.0%)
3,720 (16.0%)
3,721 (16.0%)
5,251 (18.2%)
5,303 (18.4%)
11,674 (17.0%)
11,701 (17.0%)
0.00
Endocrinologist Visit (30 days prior); n (%)
1,886 (11.3%)
1,922 (11.5%)
2,696 (11.6%)
2,851 (12.3%)
3,533 (12.2%)
3,750 (13.0%)
8,115 (11.8%)
8,523 (12.4%)
-0.02
Endocrinologist Visit (31 to 180 days prior); n (%)
1,914 (11.4%)
1,900 (11.4%)
2,567 (11.0%)
2,647 (11.4%)
3,948 (13.7%)
4,050 (14.0%)
8,429 (12.2%)
8,597 (12.5%)
-0.01
Internal medicine/family medicine visits; n (%)
12,196 (72.9%)
11,920 (71.2%)
20,638 (88.7%)
20,362 (87.5%)
24,256 (84.1%)
23,791 (82.5%)
57,090 (82.9%)
56,073 (81.4%)
0.04
Internal medicine/family medicine visits (30 days 
prior) ; n (%)
8,667 (51.8%)
8,658 (51.7%)
15,681 (67.4%)
15,619 (67.1%)
17,442 (60.5%)
17,316 (60.0%)
41,790 (60.7%)
41,593 (60.4%)
0.01
Internal medicine/family medicine visits (31 to 180 
days prior) ; n (%)
10,237 (61.2%)
10,229 (61.1%)
17,149 (73.7%)
17,062 (73.3%)
21,118 (73.2%)
21,055 (73.0%)
48,504 (70.4%)
48,346 (70.2%)
0.00
Cardiologist visit; n (%)
3,197 (19.1%)
3,226 (19.3%)
3,866 (16.6%)
3,917 (16.8%)
8,193 (28.4%)
8,255 (28.6%)
15,256 (22.2%)
15,398 (22.4%)
0.00
Number of Cardiologist visits (30 days prior); n (%)
990 (5.9%)
1,022 (6.1%)
1,192 (5.1%)
1,175 (5.1%)
2,541 (8.8%)
2,563 (8.9%)
4,723 (6.9%)
4,760 (6.9%)
0.00
Table 1

Number of Cardiologist visits (31 to 180 days prior); 
n (%)
2,698 (16.1%)
2,721 (16.3%)
3,272 (14.1%)
3,308 (14.2%)
7,110 (24.6%)
7,144 (24.8%)
13,080 (19.0%)
13,173 (19.1%)
0.00
Electrocardiogram ; n (%)
3,814 (22.8%)
3,833 (22.9%)
5,351 (23.0%)
5,482 (23.6%)
8,209 (28.5%)
8,398 (29.1%)
17,374 (25.2%)
17,713 (25.7%)
-0.01
Use of glucose test strips; n (%)
578 (3.5%)
584 (3.5%)
926 (4.0%)
953 (4.1%)
932 (3.2%)
953 (3.3%)
2,436 (3.5%)
2,490 (3.6%)
-0.01
Dialysis; n (%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
000 (0.0%)
000 (0.0%)
#DIV/0!
Naive new user v8 Copy; n (%)
1,847 (11.0%)
1,869 (11.2%)
1,991 (8.6%)
2,032 (8.7%)
1,870 (6.5%)
1,975 (6.8%)
5,708 (8.3%)
5,876 (8.5%)
-0.01
N antidiabetic drugs at index date  Copy
...mean (sd)
2.26 (0.88)
2.26 (0.86)
2.32 (0.90)
2.32 (0.88)
2.33 (0.89)
2.35 (0.88)
2.31 (0.89)
2.32 (0.88)
-0.01
...median [IQR]
2.00 [2.00, 3.00]
2.00 [2.00, 3.00]
2.00 [2.00, 3.00]
2.00 [2.00, 3.00]
2.00 [2.00, 3.00]
2.00 [2.00, 3.00]
2.00 (0.89)
2.00 (0.88)
0.00
number of different/distinct medication 
prescriptions
...mean (sd)
9.99 (4.51)
9.95 (4.43)
9.68 (4.21)
9.71 (4.16)
10.40 (4.33)
10.45 (4.40)
10.06 (4.33)
10.08 (4.33)
0.00
...median [IQR]
9.00 [7.00, 12.00]
9.00 [7.00, 12.00]
9.00 [7.00, 12.00]
9.00 [7.00, 12.00]
10.00 [7.00, 13.00]
10.00 [7.00, 13.00]
9.42 (4.33)
9.42 (4.33)
0.00
Number of Hospitalizations
...mean (sd)
0.03 (0.24)
0.03 (0.17)
0.02 (0.15)
0.02 (0.16)
0.04 (0.23)
0.04 (0.23)
0.03 (0.21)
0.03 (0.19)
0.00
...median [IQR]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 (0.21)
0.00 (0.19)
0.00
Number of hospital days
...mean (sd)
0.12 (1.00)
0.12 (0.97)
0.09 (0.81)
0.10 (0.88)
0.22 (1.56)
0.23 (1.87)
0.15 (1.22)
0.16 (1.40)
-0.01
...median [IQR]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 (1.22)
0.00 (1.40)
0.00
Number of Emergency Department (ED) visits 
...mean (sd)
0.21 (0.72)
0.21 (0.76)
0.04 (0.74)
0.04 (0.55)
0.31 (0.95)
0.31 (1.07)
0.19 (0.83)
0.19 (0.85)
0.00
...median [IQR]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 (0.83)
0.00 (0.85)
0.00
Number of Office visits
...mean (sd)
4.29 (3.42)
4.24 (3.06)
4.23 (3.30)
4.21 (3.07)
5.08 (3.83)
5.08 (3.60)
4.60 (3.56)
4.58 (3.30)
0.01
...median [IQR]
3.00 [2.00, 6.00]
3.00 [2.00, 6.00]
3.00 [2.00, 5.00]
3.00 [2.00, 5.00]
4.00 [2.00, 7.00]
4.00 [3.00, 7.00]
3.42 (3.56)
3.42 (3.30)
0.00
Number of Endocrinologist visits
...mean (sd)
0.77 (2.73)
0.85 (3.12)
0.72 (2.61)
0.87 (3.27)
1.08 (4.08)
1.22 (4.66)
0.88 (3.33)
1.01 (3.88)
-0.04
...median [IQR]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 (3.33)
0.00 (3.88)
0.00
Number of internal medicine/family medicine visits
...mean (sd)
7.13 (11.56)
7.03 (10.98)
6.26 (7.11)
6.46 (7.42)
7.46 (10.23)
7.75 (9.99)
6.97 (9.67)
7.14 (9.47)
-0.02
...median [IQR]
4.00 [0.00, 9.00]
4.00 [0.00, 9.00]
4.00 [2.00, 8.00]
4.00 [2.00, 9.00]
4.00 [2.00, 10.00]
5.00 [2.00, 10.00]
4.00 (9.67)
4.42 (9.47)
-0.04
Number of Cardiologist visits
...mean (sd)
0.78 (2.61)
0.76 (2.44)
0.61 (2.04)
0.63 (2.14)
1.33 (3.71)
1.35 (3.65)
0.95 (2.97)
0.96 (2.93)
0.00
...median [IQR]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 1.00]
0.00 [0.00, 1.00]
0.00 (2.97)
0.00 (2.93)
0.00
Number electrocardiograms received 
...mean (sd)
0.36 (0.86)
0.36 (0.86)
0.35 (0.82)
0.35 (0.83)
0.50 (1.05)
0.50 (1.07)
0.42 (0.93)
0.42 (0.94)
0.00
...median [IQR]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 1.00]
0.00 [0.00, 1.00]
0.00 (0.93)
0.00 (0.94)
0.00
Number of HbA1c tests ordered
...mean (sd)
1.36 (0.89)
1.35 (0.87)
1.28 (0.88)
1.28 (0.85)
1.56 (0.90)
1.56 (0.82)
1.42 (0.89)
1.41 (0.84)
0.01
...median [IQR]
1.00 [1.00, 2.00]
1.00 [1.00, 2.00]
1.00 [1.00, 2.00]
1.00 [1.00, 2.00]
2.00 [1.00, 2.00]
2.00 [1.00, 2.00]
1.42 (0.89)
1.42 (0.84)
0.00
Number of glucose tests ordered
...mean (sd)
0.43 (1.87)
0.43 (1.71)
0.39 (1.63)
0.39 (1.03)
0.47 (1.34)
0.47 (1.11)
0.43 (1.58)
0.43 (1.26)
0.00
...median [IQR]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 (1.58)
0.00 (1.26)
0.00
Number of lipid tests ordered
...mean (sd)
1.06 (0.96)
1.06 (0.94)
1.06 (1.29)
1.06 (1.13)
1.13 (0.88)
1.13 (0.83)
1.09 (1.05)
1.09 (0.97)
0.00
...median [IQR]
1.00 [0.00, 2.00]
1.00 [0.00, 2.00]
1.00 [0.00, 1.00]
1.00 [0.00, 2.00]
1.00 [1.00, 2.00]
1.00 [1.00, 2.00]
1.00 (1.05)
1.00 (0.97)
0.00
Number of creatinine tests ordered
...mean (sd)
0.03 (0.22)
0.03 (0.20)
0.03 (0.23)
0.04 (0.24)
0.07 (0.34)
0.07 (0.32)
0.05 (0.28)
0.05 (0.27)
0.00
...median [IQR]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 (0.28)
0.00 (0.27)
0.00
Number of BUN tests ordered
...mean (sd)
0.02 (0.16)
0.02 (0.16)
0.02 (0.18)
0.02 (0.18)
0.04 (0.28)
0.04 (0.26)
0.03 (0.22)
0.03 (0.21)
0.00
...median [IQR]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 (0.22)
0.00 (0.21)
0.00
Number of tests for microalbuminuria
...mean (sd)
0.84 (1.19)
0.85 (1.18)
0.74 (1.11)
0.74 (1.10)
0.53 (0.73)
0.54 (0.73)
0.68 (0.99)
0.68 (0.99)
0.00
...median [IQR]
0.00 [0.00, 2.00]
0.00 [0.00, 2.00]
0.00 [0.00, 2.00]
0.00 [0.00, 2.00]
0.00 [0.00, 1.00]
0.00 [0.00, 1.00]
0.00 (0.99)
0.00 (0.99)
0.00
Total N distinct ICD9/ICD10 diagnoses at the 3rd 
digit level Copy
...mean (sd)
5.56 (5.86)
5.43 (6.00)
2.09 (3.20)
2.05 (3.27)
5.91 (6.84)
5.82 (6.92)
4.53 (5.60)
4.45 (5.69)
0.01
...median [IQR]
5.00 [0.00, 8.00]
5.00 [0.00, 8.00]
0.00 [0.00, 4.00]
0.00 [0.00, 4.00]
4.00 [0.00, 9.00]
4.00 [0.00, 9.00]
2.89 (5.60)
2.89 (5.69)
0.00
Use of thiazide; n (%)
2,040 (12.2%)
2,060 (12.3%)
2,782 (12.0%)
2,737 (11.8%)
4,125 (14.3%)
4,100 (14.2%)
8,947 (13.0%)
8,897 (12.9%)
0.00
Use of beta blockers; n (%)
6,033 (36.0%)
6,038 (36.1%)
8,159 (35.1%)
8,198 (35.2%)
13,867 (48.1%)
13,913 (48.2%)
28,059 (40.8%)
28,149 (40.9%)
0.00
Use of calcium channel blockers; n (%)
4,836 (28.9%)
4,820 (28.8%)
6,641 (28.5%)
6,697 (28.8%)
9,762 (33.8%)
9,796 (34.0%)
21,239 (30.8%)
21,313 (31.0%)
0.00
Table 1