Replication of the SAVOR-TIMI Diabetes Trial in Healthcare Claims
Conditions: Diabetes
Sponsor: Brigham and Women's Hospital

Replication of the SAVOR-TIMI Diabetes Trial in Healthcare Claims 
NCT03936023 
 
December 27, 2019

Effectiveness research with Real World Data to support FDA’s regulatory decision making 
 
 
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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 
 
Saxagliptin and Cardiovascular Outcomes in Patients with Type 2 Diabetes Mellitus (SAVOR- TIMI 53 trial) 
 
1.2 Intended aim(s) 
 
The cardiovascular safety and efficacy of many current antihyperglycemic agents, including saxagliptin, a dipeptidyl 
peptidase 4 (DPP-4) inhibitor, are unclear. This trial was designed to evaluate the safety and efficacy of saxagliptin with 
respect to cardiovascular outcomes in patients with diabetes mellitus who are at risk for cardiovascular events. 
 
1.3 Primary endpoint for replication and RCT finding 
Composite of CV death, nonfatal myocardial infarction, or nonfatal ischemic stroke 
 
1.4 Required power for primary endpoint and noninferiority margin (if applicable) 
 
85% power to identify a 17% relative reduction of the primary end point with saxagliptin versus placebo and 98% power to 
test for noninferiority of saxagliptin versus placebo (reject the upper limit of 95% CI for an HR 1.3 at a 1-sided α of .025) 
 
1.5 Primary trial estimate targeted for replication 
 
HR = 1.00 (95% CI 0.89-1.12) comparing saxagliptin to placebo (Scirica et al., 2013) 
 
 
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 
 
 
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5. Cohort Identification  
 
5.1 Cohort Summary 
This study will involve a new user, parallel group, cohort study design comparing saxagliptin to the 2nd generation sulfonylurea 
(SU) antidiabetic class as a proxy for placebo. 2nd generation SUs are not known to have an impact on the outcome of interest. In 
addition, SUs were the most frequent background treatment in SAVOR-TIMI53 (after metformin), and DPP4i and SUs are 
preferentially prescribed to similarly older patients in real world (Patorno et al., 2019). The patients will be required to have 
continuous enrollment during the baseline period of 180 days before initiation of saxagliptin 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 saxagliptin in the U.S. started on July 31, 2009       
• For Marketscan: July 31, 2009-Dec 31, 2017 (end of data availability).  
• For Medicare: Jan 1, 2012-Dec 31, 2017 (start- end of data availability). 
• For Optum: July 31, 2009-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 
 
  
Optum 
Truven 
Medicare 

Effectiveness research with Real World Data to support FDA’s regulatory decision making: Protocol Template 
 
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Less 
Excluded 
Patients 
Remaining 
Patients 
Less 
Excluded 
Patients 
Remaining 
Patients 
Less 
Excluded 
Patients 
Remaining 
Patients 
All patients in the database 
  
74,864,884   
191,990,035   
23,466,175 
Patients who used exposure or a reference between 20 January 2010 
to Dec 2017 (for Marketscan)/March 2019 (for Optum) and 01 
January 2012-December 2017 for Medicare 
-
73,333,681 1,531,203 
-
189,850,391 2,139,644 
-
20,002,243 3,463,932 
Patients who have continuous 6 months registration in the database  
-198,718 
1,332,485 
-233,411 
1,906,233 
-926,605 
2,537,327 
Patients without prior use of reference 
-837,680 
494,805 
-1,282,498 
623,735 
-1,516,234 
1,021,093 
Patients without prior use of exposure 
-58,834 
435,971 
-71,555 
552,180 
-57,547 
963,546 
Excluded because patient qualified in >1 exposure category 
-193 
435,778 
-301 
551,879 
-111 
963,435 
Patients who did not have missing age information 
-13 
435,765 
0 
551,879 
0 
963,435 
Patients who did not have missing gender information 
-26 
435,739 
0 
551,879 
0 
963,435 
Excluded based on Inclusion 1- DM Type 2 
-20,512 
415,227 
-49,327 
502,552 
-8,942 
954,493 
Excluded based on Inclusion 2- Age >=40 
-8,101 
407,126 
-17,260 
485,292 
0 
954,493 
Excluded based on Inclusion 4- High risk for a CV event defined as 
having either established CV disease and/or multiple risk factors 
-34,138 
372,988 
-73,801 
411,491 
-3,577 
950,916 
Excluded based on Exclusion1- CCI >=10 
-3,466 
369,522 
-1,659 
409,832 
-17,277 
933,639 
Excluded based on Exclusion 2- treatment with an incretin-based 
therapy such as DPP-4 inhibitors and/or GLP-1 mimetics 
-13,198 
356,324 
-18,748 
391,084 
-33,418 
900,221 
Excluded based on Exclusion 3- Acute vascular (cardiac or stroke) 
event <2 months [i.e. ACS/unstable angina OR Any stroke (inpatient, 
any)] 
-766 
355,558 
-1,546 
389,538 
-1,979 
898,242 
Excluded based on Exclusion 4- chronic dialysis or renal transplant 
-592 
354,966 
-434 
389,104 
-2,718 
895,524 
Excluded based on Exclusion 5- Pregnancy 
-7 
354,959 
-11 
389,093 
-9 
895,515 
Excluded based on Exclusion 6- HIV/AIDS (dx and meds) with ICD10 
CODES 
-129 
354,830 
-104 
388,989 
-206 
895,309 
Excluded based on Exclusion 7- Lupus 
-174 
354,656 
-122 
388,867 
-517 
894,792 
Excluded based on Exclusion 8- long-term (>30 consecutive days) oral 
corticosteroids use 
-2,286 
352,370 
-2,495 
386,372 
-7,501 
887,291 
Excluded based on Exclusion 9- Morbid Obesity 
-3,600 
348,770 
-2,126 
384,246 
-6,087 
881,204 
Excluded based on Exclusion 13- Non-compliance 
-1408 
347,362 
-447 
383,799 
-2,954 
878,250 

Effectiveness research with Real World Data to support FDA’s regulatory decision making 
 
 
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Final cohort 
  
347,362 
  
383,799 
  
878,250 
* Medicare database includes only patients with at least one diagnosis for diabetes, heart failure, or cerebrovascular disease. 
 
6. Variables  
 
6.1 Exposure-related variables:  
 
Study drug:  
The study exposure of interest is initiation of saxagliptin. Initiation will be defined by no use of saxagliptin or a comparator in the 
prior 6 months before treatment initiation (washout period).  
 
Comparator agents: 
• Initiators of saxagliptin will be compared to initiators of- 
o 2nd generation sulfonylureas 
 
Because saxagliptin and comparators are frequently used as second or third line treatments of T2DM, we expect it to be unlikely 
that saxagliptin 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:  

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6.3.1 Outcome variables 
 
Effectiveness outcomes of interest (definitions provided in Appendix A):  
 
• Primary outcome: 3-point major adverse cardiovascular events (MACE), i.e., non-fatal myocardial infarction, non-fatal stroke, 
or CV mortality 
• Secondary outcomes: Individual MACE 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. Severe hypoglycemia (we expect to see protective effect; American Diabetes Association, 2018) 
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.  
Outcome 
Hospital Discharge Code(s) 
Comments 
Severe hypoglycemia 
Severe hypoglycemia 
Any-position ED or primary inpatient ICD-9 diagnosis: 251.0, 251.1x, 251.2x, or 250.8x.  
Outcomes 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 
Note- The  corresponding ICD-10 
codes will  be used  also 

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For the AT analyses, the follow-up will start the day after initiation of liraglutide 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,  
• 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 (saxagliptin 
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 glimepiride to glipizide 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 
saxagliptin 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 links:  
Optum- https://bwh-dope.aetion.com/#/projects/details/641/results/29994/result/0  
Marketscan-  https://bwh-dope.aetion.com/#/projects/details/642/results/29995/result/0  
Medicare- https://bwh-dope.aetion.com/#/projects/details/643/results/29996/result/0  
 

Effectiveness research with Real World Data to support FDA’s regulatory decision making: Protocol Template 
 
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Date conducted: rerun on 01/07/2019 
 
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 links:  
Optum- https://bwh-dope.aetion.com/#/projects/details/641/results/29997/result/1    
Marketscan- https://bwh-dope.aetion.com/#/projects/details/642/results/29998/result/1   
Medicare- https://bwh-dope.aetion.com/#/projects/details/643/results/29999/result/1     
 
Date conducted: rerun on 01/07/2019 
 
• 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). 
 
• 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: 
12/19/18 
Reasons for stopping 
analysis (if required): 
 

Effectiveness research with Real World Data to support FDA’s regulatory decision making 
 
 
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9. Balance Assessment after PS matching 
 
Aetion report name: 
Optum- https://bwh-dope.aetion.com/projects/details/641/results/44771/result/0 
Marketscan- https://bwh-dope.aetion.com/projects/details/642/results/44772/result/0 
Medicare- https://bwh-dope.aetion.com/projects/details/643/results/45431/result/0 
 
Date conducted:  11/18/2019 (Medicare 11/30/2019) 
 
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.  
 
• Report covariate balance after matching. 
 
Note- For Table 1, please refer to Appendix B. 
 
• Report reasons for censoring by treatment group. 
  
Overall 
Referent 
Exposure 
Dummy Outcome 
0 (0.00%) 
0 (0.00%) 
0 (0.00%) 
Death 
1,783 (0.98%) 
1,051 (1.15%) 
732 (0.80%) 
Start of an additional exposure 
10,211 (5.61%) 
976 (1.07%) 
9,235 (10.14%) 
End of index exposure 
122,449 (67.23%) 
61,560 (67.60%) 
60,889 (66.86%) 
Specified date reached 
11,855 (6.51%) 
7,184 (7.89%) 
4,671 (5.13%) 
End of patient enrollment 
25,411 (13.95%) 
13,085 (14.37%) 
12,326 (13.54%) 

Effectiveness research with Real World Data to support FDA’s regulatory decision making: Protocol Template 
 
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Switch to other SUs (for censoring) + nursing home admission 
10,419 (5.72%) 
7,208 (7.92%) 
3,211 (3.53%) 
 
• Report follow-up time by treatment group. 
 
Median Follow-Up Time (Days) [IQR] 
Patient Group 
Optum 
Marketscan 
Medicare 
Overall Patient Population 
139 [58-344] 
153 [82-367] 
155 [85-373] 
Referent 
144 [78-354] 
180 [102-432] 
180 [102-
432] 
Exposure 
132 [58-331] 
140 [58-323] 
140 [58-323] 
 
• Report overall risk of the primary outcome. 
  
Optum 
Marketscan 
Medicare 
Risk per 1,000 patients 
13.68 
16.21 
38.38 
 
10. Final Power Assessment 
 
Date conducted: 2/1/2019 
 
• 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 Pooled 

Effectiveness research with Real World Data to support FDA’s regulatory decision making 
 
 
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o Optum 
 
 
o Marketscan 
Non-inferiority Analysis
Number of patients matched
Reference
91,063
Exposed
91,063
Risk per 1,000 patients
22.76
Assumed HR from RCT
1
Alpha (2-sided)
0.05
Non-inferiority margin
1.3
Number of events expected
4145.18776
Power
1
Superiority Analysis
Number of patients matched
Reference
91,063
Exposed
91,063
Risk per 1,000 patients
22.76
Desired HR from RCT
0.83
Alpha (2-sided)
0.05
Number of events expected
4145.18776
Power
0.999973077
Non-inferiority Analysis
Number of patients matched
Reference
20,772
Exposed
20,772
Risk per 1,000 patients
13.68
Assumed HR from RCT
1
Alpha (2-sided)
0.05
Non-inferiority margin
1.3
Number of events expected
568.32192
Power
0.878466057
Superiority Analysis
Number of patients matched
Reference
20,772
Exposed
20,772
Risk per 1,000 patients
13.68
Desired HR from RCT
0.83
Alpha (2-sided)
0.05
Number of events expected
568.32192
Power
0.602983034

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o Medicare 
 
 
• 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 
Non-inferiority Analysis
Number of patients matched
Reference
29,150
Exposed
29,150
Risk per 1,000 patients
16.21
Assumed HR from RCT
1
Alpha (2-sided)
0.05
Non-inferiority margin
1.3
Number of events expected
945.043
Power
0.980903542
Superiority Analysis
Number of patients matched
Reference
29,150
Exposed
29,150
Risk per 1,000 patients
16.21
Desired HR from RCT
0.83
Alpha (2-sided)
0.05
Number of events expected
945.043
Power
0.817020552
Non-inferiority Analysis
Number of patients matched
Reference
41,141
Exposed
41,141
Risk per 1,000 patients
38.38
Assumed HR from RCT
1
Alpha (2-sided)
0.05
Non-inferiority margin
1.3
Number of events expected
3157.98316
Power
0.999999969
Superiority Analysis
Number of patients matched
Reference
41,141
Exposed
41,141
Risk per 1,000 patients
38.38
Desired HR from RCT
0.83
Alpha (2-sided)
0.05
Number of events expected
3157.98316
Power
0.999472659

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

Effectiveness research with Real World Data to support FDA’s regulatory decision making: Protocol Template 
 
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• In the PS-matched cohort from Section 9, calculate the HR for each outcome for Saxagliptin versus referent patients using a Cox 
proportional hazards model.  
 
 
13.2 
For secondary analyses: 
 
• In the pre-matched cohort, 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 Saxagliptin 
versus referent patients using a Cox proportional hazards model, adjusting for deciles of the PS. 
 
14.  Requested Results  
 
14.1 
Results from primary and secondary analyses: 
 
Separately for each endpoint: 
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 
 

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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)  
 
Scirica BM, Bhatt DL, Braunwald E, Steg PG, Davidson J, Hirshberg B, Ohman P, Frederich R, Wiviott SD, Hoffman EB, Cavender MA. 
Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. New England Journal of Medicine. 2013; 
369(14):1317-26. 
 
  
 

#
SAVOR-TIMI 53 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
Saxagliptin 5 mg QD (2.5 mg in subjects with moderate/severe renal impairment) 
vs placebo
Saxagliptin vs. 2nd generation sulfonylurea
Intermediate mapping in claims
Poor mapping or cannot be measured in claims 
Composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal 
ischemic stroke HR = 1.00 (95% CI 0.89-1.12)
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), as the 
principal (primary) or the next (secondary) diagnosis
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
1
Diagnosed with T2DM based on the current American Diabetes Association 
guidelines
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
2 Age ≥40 years
Age ≥40 years at drug initiation
3 Glycated hemoglobin level of ≥6.5% (based on the last measured and 
documented laboratory measurement in the previous 6 months)
N/A
4 High risk for a CV event defined as having either established CV disease and/or 
-
• History of established cardiovascular disease
-
– Ischemic heart disease, and/or
Measured 180 days prior to drug initiation in any diagnosis position and inpatient or outpatient 
care setting - Ischemic heart disease
410.xx-414.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- Negative trial
EXPOSURE vs. COMPARISON
INCLUSION CRITERIA
Appendix A

– Peripheral vascular disease (eg, intermittent claudication), and/or
Measured 180 days prior to drug initiation in any diagnosis position and inpatient or outpatient 
care setting- Peripheral vascular disease 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
– Ischemic stroke
Measured 180 days prior to drug initiation in any diagnosis position and inpatient or outpatient 
care setting - Any stroke: ICD-9 Dx: 433.xx, 434.xx, 436.xx
• Multiple risk factors for vascular disease
-
– At least 55 years of age (men) or 60 years of age (women), AND at  least one of 
the following additional risk factors
At least 55 years of age (men) or 60 years of age (women) at drug initiation, AND 
* Dyslipidemia (based on the last measured and documented laboratory 
measurement in the previous 6 months and defined as at least 1 of the 
following):
Measured 180 days prior to drug initiation in any diagnosis position and inpatient or outpatient 
care setting - Hyperlipidemia 272.0x-272.4x
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
◦ High level of low-density lipoprotein cholesterol (LDL-C), defined as 
N130 mg/dL (N 3.36 mmol/L) regardless of lipid-lowering therapy
N/A/Use the labs whenever possible
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
◦ Low level of high-density lipoprotein cholesterol (HDL-C), defined as 
b40 mg/dL (b1.04 mmol/L) for men or b50 mg/dL (b1.30 mmol/L) for 
women
N/A/Use the labs whenever possible
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
* Hypertension, as confirmed at the enrolment visit
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
◦ BP N140/N90 mm Hg, or
◦ BP N130/N80 mm Hg on BP-lowering agent
Measured as a dispensing for one of the following180 days prior to drug initiation  -
Diuretics/ACE/ARB/Calcium channel blockers/Beta blockers
* Currently smoking, as confirmed at the enrolment visit
Measured 180 days prior to drug initiation in any diagnosis position and inpatient or outpatient 
care setting - Smoking
ICD 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
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 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
4a
4b
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 
Appendix A

5
Women of childbearing potential must take precautions to avoid pregnancy 
throughout the study and for 4 weeks after intake of the last dose. Men 
participating in the study should also take precautions not to father a child while 
participating in the study and for 4 weeks after intake of the last dose.
Since this is an inclusion criteria, it's difficult to implement the contraceptive use requirement 
here, but we have pregnancy as an exclusion criteria later, so this requirement is implemented 
then.
6 Provision of informed consent before any study specific procedures
N/A
1
Any conditions that, in the opinion of the investigator, may render the patient 
unable to complete the study including non-CV disease (eg, active malignancy, 
cardiomyopathy, cirrhosis, or chronic lung disease) with a likely fatal outcome 
within 5 years
Measured 180 days prior to drug initiation  - CCI >= 95 percentile
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.
2 Current or previous (within 6 months) treatment with an incretin-based therapy 
such as DPP-4 inhibitors and/or GLP-1 mimetics
Measured 180 days prior to drug initiation  - Current or previous (prior 6 months) occurrence of 
incretin-based mimetics. Drugs in the incretin mimetic class include exenatide, liraglutide, 
sitagliptin, saxagliptin, alogliptin, and linagliptin 
 Source- 
https://www.fda.gov/Drugs/DrugSafety/InformationbyDrugClass/ucm343516.htm
3 Acute vascular (cardiac or stroke) event <2 months before randomization
Measured 60 days prior to drug initiation in any diagnosis/procedure position and inpatient care 
setting -  
ACS/unstable angina 411.xx
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
4 Initiation of chronic dialysis and/or renal transplant and/or a serum creatinine 
>6.0 mg/dL
Measured 180 days prior to drug initiation in any diagnosis position and inpatient or outpatient 
care setting -
Kidney transplant
Codes include:
-ICD9 dx codes:
 o V42.0x, Kidney transplant status
o 996.81 Complications of transplanted kidney
-ICD9 prox codes: 
o 55.6x, Transplant of kidney (Exclude 55.61)
- CPT4 codes:
o 50360, Renal allotransplantation, implantation, graft, w/o donor & recipient nephrectomy
o 50365, Renal allotransplantation, implantation, graft, w/ donor & recipient nephrectomy
Dialysis (Please see Dialysis 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
5
Pregnant or breastfeeding
Measured 180 days prior to drug initiation in any diagnosis position and inpatient or outpatient 
care setting- 
Pregnancy : Please see Pregnancy sheet.
6
History of human immunodeficiency virus
Measured 180 days prior to drug initiation in any diagnosis/procedure position and inpatient 
care setting or a dispensing of one of the following drugs -  
HIV
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
EXCLUSION CRITERIA
Appendix A

7
Patients being treated for severe autoimmune diseases such as lupus
Measured 180 days prior to drug initiation in any diagnosis/procedure position and inpatient 
care setting
Lupus
373.34 - (ICD9) DISCOID LUPUS ERYTHEMATOSUS OF EYELID
710.0 - (ICD9) SYSTEMIC LUPUS ERYTHEMATOSUS
8
Any patient currently receiving long-term (>30 consecutive days) treatment with 
an oral steroid
Measured 180 days prior to drug initiation as a dispensing of one of the following drugs - 
Oral corticosteroids:-  Cortisone, hydrocortisone, prednisone, prednisolone, methylprednisolone, 
triamcinolone, dexamethasone, betamethasone. 
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
9 Patients with
9a
• Body mass index >50 kg/m2
Measured 180 days prior to drug initiation in any diagnosis/procedure position and inpatient 
care setting-
Morbid Obesity
278.01 - (ICD9) MORBID OBESITY
9b
• Last measured HbA1c ≥12%
N/A
9c
• Sustained BP >180/100 mm Hg
N/A
9d
• LDL-C >250 mg/dL (>6.48 mmol/L) (based on the last measured and 
documented laboratory measurement in the previous 6 months) regardless of 
lipid-lowering therapy
N/A
9e
• Triglycerides >1,000 mg/dL (N11.3 mmol/L) (based on the last measured and 
documented laboratory measurement in the previous 6months)
N/A
9f
• HDL-C b25 mg/dL (<0.64 mmol/L) (based on the last measured and 
documented laboratory measurement in the previous 6 months)
N/A
9g
• Known liver function tests >3 times upper limit of normal (ULN) (based on the 
last measured and documented laboratory measurement in the previous 6 
months)
N/A
10
Involvement in the planning and/or conduct of the study (applies to both 
AstraZeneca and Bristol-- Myers Squibb or representative staff and/or staff at the 
study site)
N/A
11 Previous randomization in the present study
N/A
12 Participation in another clinical study with an investigational product and/or 
intervention within 30 days before visit 1
N/A
13
Individuals at risk for poor protocol or medication compliance
Measured 180 days prior to drug initiation in any diagnosis/procedure position and inpatient 
care setting-
Non-compliance
V15.81 - (ICD9) PERSONAL HISTORY OF NONCOMPLIANCE WITH MEDICAL TREATMENT PRESENTING 
HAZARDS TO HEALTH
V45.12 - (ICD9) NONCOMPLIANCE WITH RENAL DIALYSIS
Appendix A

Trial ID 
Neg5
Trial Name (with web links)
SAVOR- TIMI 53
Trial Name (with pdf links)
SAVOR- TIMI 53
NCT
NCT01107886  
Trial category
Negative trial
Therapeutic Area
Endocrinology
RCT Category  
2b- Failed S with NI- No label change
Brand Name
Onglyza
Generic Name
saxagliptin
Sponsor
AstraZeneca|Bristol-Myers Squibb
Year
2013
Measurable endpoint
Primary composite endpoint of Cardiovascular Death (CV Death), Non-fatal 
Myocardial Infarction (MI), or Non-fatal Ischaemic Stroke
Exposure
Saxagliptin
Comparator
Placebo
Population
patients with type 2 diabetes who had a history of, or were at risk for, 
cardiovascular events. The concomitant Anti-hyperglycemic and Cardiovascular 
Medications- 75% aspirin, 78% statins, 53% ACE, 61% beta-blockers
Trial finding
HR = 1.00 (95% CI 0.89-1.12)
Notes
No. of Patients
18,206
Non-inferiority margin
HR = 1.3
Assay Sens. Endpoint
From trial- Hospitalization for heart failure. Alternative suggestion- all-cause 
mortality/MACE/hypoglycemia
Assay Sens. Finding
3.5% vs. 2.8%; hazard ratio, 1.27; 95% CI, 1.07 to 1.51; P=0.007
Comments/Notes
It is hard to replicate, so alternative option would be to replicate "all-cause 
mortality"/ MACE/hypoglycemia as shown in this Taiwan study comparing DPP4i 
to sulfonylureas - http://annals.org/aim/article-abstract/2456123/effects-
clinical-outcomes-adding-dipeptidyl-peptidase-4-inhibitors-versus-sulfonylureas  
Power
0.85 power to identify a 17% relative reduction of the primary end point with 
saxagliptin versus placebo and 98% power to test for noninferiority of saxagliptin 
versus placebo (reject the upper limit of 95% CI for a hazard ratio <1.3 at a 1-sided 
α of .025)
Blinding
Double-blinded
Statistical Method
Superiority and non-inferiority
Approval indication
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)
• 41 - Other died status or Expired in medical facility (Hospice claims only) (depends on year)
Appendix A

• 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 and Optum Clinformatics at a later date. We will conduct secondary analyses using CV 
mortality at that time.
Appendix A

ESRD, defined as 2 codes (either inpatient or outpatient), separated by at least 30 days 
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 ofservice per day; for patients 12 19 and
Appendix A

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
G0316 G0319 ESRD related services during thecourseoftreatment for patients 12 19 and 20 yrs ofageand
Appendix A

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

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

AFTER PS MATCHING
BEFORE PS MATCHING
Optum
MarketScan
Medicare
The c-statistics for the propensity score model, pre-matching was 0.724. The post-matching c-statistic 
was 0.524.
The c-statistics for the propensity score model, pre-matching was 0.742. The post-matching 
c-statistic was 0.521.
The c-statistics for the propensity score model, pre-matching was 0.69. The post-matching c-statistic 
was 0.519.
Appendix B

Variable
Reference- 2nd 
Generation SUs
Exposure- Saxagliptin
Reference- 2nd 
Generation SUs
Exposure- Saxagliptin
Reference- 2nd 
Generation SUs
Exposure- 
Saxagliptin
Reference- 2nd 
Generation SUs
Exposure- Saxagliptin
St. Diff.
Number of patients
                                       326,256                                           20,779 
354,219
                                      
29,159
                                         
833,830
                                    
41,144
                       
                                  1,514,305                                           91,082 
Age
...mean (sd)
69.39 (8.53)
66.00 (8.42)
66.17 (9.47)
64.01 (8.25)
74.47 (7.32)
73.88 (6.93)
71.43 (8.13)
68.92 (7.72)
0.32
...median [IQR]
69.00 [64.00, 75.00]
65.00 [60.00, 71.00]
64.00 [60.00, 72.00]
62.00 [59.00, 68.00]
73.00 [68.00, 79.00]3.00 [68.00, 78.00]
70.03 (8.13)
67.65 (7.72)
0.30
Age categories 
...18 - 54; n (%)
8,369 (2.6%)
923 (4.4%)
14,650 (4.1%)
1,527 (5.2%)
0 (0.0%)
0 (0.0%)
23,019 (1.5%)
2,450 (2.7%)
-0.08
...55 - 64; n (%)
81,938 (25.1%)
8,844 (42.6%)
180,842 (51.1%)
17,427 (59.8%)
14,366 (1.7%)
758 (1.8%)
277,146 (18.3%)
27,029 (29.7%)
-0.27
...65 - 74; n (%)
144,642 (44.3%)
7,473 (36.0%)
86,662 (24.5%)
6,582 (22.6%)
457,643 (54.9%)
23,716 (57.6%)
688,947 (45.5%)
37,771 (41.5%)
0.08
...>= 75; n (%)
91,307 (28.0%)
3,539 (17.0%)
72,065 (20.3%)
3,623 (12.4%)
361,821 (43.4%)
16,670 (40.5%)
525,193 (34.7%)
23,832 (26.2%)
0.19
Gender 
...Males; n (%)
182,712 (56.0%)
12,150 (58.5%)
220,912 (62.4%)
18,053 (61.9%)
392,996 (47.1%)
18,280 (44.4%)
796,620 (52.6%)
48,483 (53.2%)
-0.01
...Females; n (%)
143,544 (44.0%)
8,629 (41.5%)
133,307 (37.6%)
11,106 (38.1%)
440,834 (52.9%)
22,864 (55.6%)
717,685 (47.4%)
42,599 (46.8%)
0.01
Race 
...White; n (%)
N/A
N/A
N/A
N/A
646,820 (77.6%)
30,782 (74.8%)
646,820 (77.6%)
30,782 (74.8%)
0.07
...Black; n (%)
N/A
N/A
N/A
N/A
96,934 (11.6%)
4,514 (11.0%)
96,934 (11.6%)
4,514 (11.0%)
0.02
...Asian; n (%)
N/A
N/A
N/A
N/A
27,110 (3.3%)
1,951 (4.7%)
27,110 (3.3%)
1,951 (4.7%)
-0.07
...Hispanic; n (%)
N/A
N/A
N/A
N/A
32,513 (3.9%)
1,896 (4.6%)
32,513 (3.9%)
1,896 (4.6%)
-0.03
...North American Native; n (%)
N/A
N/A
N/A
N/A
5,488 (0.7%)
541 (1.3%)
5,488 (0.7%)
541 (1.3%)
-0.06
...Other/Unknown; n (%)
N/A
N/A
N/A
N/A
24,965 (3.0%)
1,460 (3.5%)
24,965 (3.0%)
1,460 (3.5%)
-0.03
Region   (lumping missing&other category with West)
...Northeast; n (%)
33,392 (10.2%)
2,359 (11.4%)
57,349 (16.2%)
5,959 (20.4%)
140,063 (16.8%)
8,083 (19.6%)
230,804 (15.2%)
16,401 (18.0%)
-0.08
...South; n (%)
150,301 (46.1%)
11,451 (55.1%)
102,784 (29.0%)
6,008 (20.6%)
354,867 (42.6%)
18,938 (46.0%)
607,952 (40.1%)
36,397 (40.0%)
0.00
...Midwest; n (%)
66,450 (20.4%)
3,702 (17.8%)
136,078 (38.4%)
14,097 (48.3%)
201,736 (24.2%)
7,132 (17.3%)
404,264 (26.7%)
24,931 (27.4%)
-0.02
...West; n (%)
76,113 (23.3%)
3,267 (15.7%)
54,627 (15.4%)
2,738 (9.4%)
137,164 (16.4%)
6,991 (17.0%)
267,904 (17.7%)
12,996 (14.3%)
0.09
...Unknown+missing; n (%)
N/A
N/A
3,381 (1.0%)
357 (1.2%)
N/A
N/A
3,381 (1.0%)
357 (1.2%)
-0.02
CV Covariates
Ischemic heart disease; n (%)
77,524 (23.8%)
4,616 (22.2%)
77,899 (22.0%)
6,045 (20.7%)
244,727 (29.3%)
11,984 (29.1%)
400,150 (26.4%)
22,645 (24.9%)
0.03
Acute MI; n (%)
5,645 (1.7%)
244 (1.2%)
5,977 (1.7%)
300 (1.0%)
13,796 (1.7%)
471 (1.1%)
25,418 (1.7%)
1,015 (1.1%)
0.05
ACS/unstable angina; n (%)
5,370 (1.6%)
311 (1.5%)
5,093 (1.4%)
374 (1.3%)
12,672 (1.5%)
589 (1.4%)
23,135 (1.5%)
1,274 (1.4%)
0.01
Old MI; n (%)
11,253 (3.4%)
524 (2.5%)
6,653 (1.9%)
415 (1.4%)
32,969 (4.0%)
1,318 (3.2%)
50,875 (3.4%)
2,257 (2.5%)
0.05
Stable angina; n (%)
11,196 (3.4%)
662 (3.2%)
9,411 (2.7%)
729 (2.5%)
28,061 (3.4%)
1,494 (3.6%)
48,668 (3.2%)
2,885 (3.2%)
0.00
Coronary atherosclerosis and other forms of chronic ischem
71,276 (21.8%)
4,252 (20.5%)
71,475 (20.2%)
5,543 (19.0%)
232,887 (27.9%)
11,360 (27.6%)
375,638 (24.8%)
21,155 (23.2%)
0.04
Other atherosclerosis with ICD10 ; n (%)
3,928 (1.2%)
253 (1.2%)
3,704 (1.0%)
366 (1.3%)
15,620 (1.9%)
937 (2.3%)
23,252 (1.5%)
1,556 (1.7%)
-0.02
Previous cardiac procedure (CABG or PTCA or Stent) ; n (%)
3,263 (1.0%)
166 (0.8%)
4,032 (1.1%)
199 (0.7%)
6,282 (0.8%)
233 (0.6%)
13,577 (0.9%)
598 (0.7%)
0.02
History of CABG or PTCA; n (%)
18,034 (5.5%)
932 (4.5%)
9,694 (2.7%)
693 (2.4%)
68,080 (8.2%)
2,852 (6.9%)
95,808 (6.3%)
4,477 (4.9%)
0.06
Any stroke; n (%)
21,878 (6.7%)
1,285 (6.2%)
20,004 (5.6%)
1,583 (5.4%)
77,966 (9.4%)
3,882 (9.4%)
119,848 (7.9%)
6,750 (7.4%)
0.02
Ischemic stroke (w and w/o mention of cerebral infarction)
21,575 (6.6%)
1,270 (6.1%)
19,796 (5.6%)
1,569 (5.4%)
76,960 (9.2%)
3,839 (9.3%)
118,331 (7.8%)
6,678 (7.3%)
0.02
Hemorrhagic stroke; n (%)
640 (0.2%)
30 (0.1%)
511 (0.1%)
33 (0.1%)
2,152 (0.3%)
90 (0.2%)
3,303 (0.2%)
153 (0.2%)
0.00
TIA; n (%)
4,889 (1.5%)
289 (1.4%)
4,657 (1.3%)
335 (1.1%)
17,677 (2.1%)
873 (2.1%)
27,223 (1.8%)
1,497 (1.6%)
0.02
Other cerebrovascular disease; n (%)
6,171 (1.9%)
298 (1.4%)
4,655 (1.3%)
289 (1.0%)
23,758 (2.8%)
984 (2.4%)
34,584 (2.3%)
1,571 (1.7%)
0.04
Late effects of cerebrovascular disease; n (%)
6,142 (1.9%)
291 (1.4%)
3,963 (1.1%)
220 (0.8%)
22,614 (2.7%)
826 (2.0%)
32,719 (2.2%)
1,337 (1.5%)
0.05
Cerebrovascular procedure; n (%)
295 (0.1%)
15 (0.1%)
335 (0.1%)
29 (0.1%)
801 (0.1%)
26 (0.1%)
1,431 (0.1%)
70 (0.1%)
0.00
Heart failure (CHF); n (%)
29,195 (8.9%)
1,231 (5.9%)
23,300 (6.6%)
1,274 (4.4%)
99,329 (11.9%)
4,239 (10.3%)
151,824 (10.0%)
6,744 (7.4%)
0.09
Peripheral Vascular Disease (PVD) or PVD Surgery ; n (%)
25,929 (7.9%)
1,480 (7.1%)
20,526 (5.8%)
1,704 (5.8%)
94,220 (11.3%)
4,860 (11.8%)
140,675 (9.3%)
8,044 (8.8%)
0.02
Atrial fibrillation; n (%)
26,603 (8.2%)
1,219 (5.9%)
23,512 (6.6%)
1,393 (4.8%)
104,219 (12.5%)
4,452 (10.8%)
154,334 (10.2%)
7,064 (7.8%)
0.08
Other cardiac dysrhythmia; n (%)
29,510 (9.0%)
1,327 (6.4%)
23,209 (6.6%)
1,413 (4.8%)
105,401 (12.6%)
4,442 (10.8%)
158,120 (10.4%)
7,182 (7.9%)
0.09
Cardiac conduction disorders; n (%)
9,152 (2.8%)
406 (2.0%)
7,170 (2.0%)
396 (1.4%)
35,402 (4.2%)
1,404 (3.4%)
51,724 (3.4%)
2,206 (2.4%)
0.06
Other CVD; n (%)
37,124 (11.4%)
1,993 (9.6%)
32,930 (9.3%)
2,357 (8.1%)
126,705 (15.2%)
6,323 (15.4%)
196,759 (13.0%)
10,673 (11.7%)
0.04
Diabetes-related complications
Diabetic retinopathy; n (%)
18,310 (5.6%)
1,007 (4.8%)
13,846 (3.9%)
1,018 (3.5%)
51,299 (6.2%)
2,806 (6.8%)
83,455 (5.5%)
4,831 (5.3%)
0.01
Diabetes with other ophthalmic manifestations; n (%)
1,878 (0.6%)
75 (0.4%)
10,886 (3.1%)
927 (3.2%)
21,591 (2.6%)
1,320 (3.2%)
34,355 (2.3%)
2,322 (2.5%)
-0.01
Retinal detachment, vitreous hemorrhage, vitrectomy; n (%
1,193 (0.4%)
81 (0.4%)
1,053 (0.3%)
86 (0.3%)
3,016 (0.4%)
146 (0.4%)
5,262 (0.3%)
313 (0.3%)
0.00
Retinal laser coagulation therapy; n (%)
1,780 (0.5%)
105 (0.5%)
2,021 (0.6%)
164 (0.6%)
4,269 (0.5%)
275 (0.7%)
8,070 (0.5%)
544 (0.6%)
-0.01
Occurrence of Diabetic Neuropathy ; n (%)
53,488 (16.4%)
2,860 (13.8%)
34,395 (9.7%)
2,354 (8.1%)
141,342 (17.0%)
7,059 (17.2%)
229,225 (15.1%)
12,273 (13.5%)
0.05
Occurrence of diabetic nephropathy  with ICD10; n (%)
42,970 (13.2%)
1,931 (9.3%)
18,676 (5.3%)
1,038 (3.6%)
70,413 (8.4%)
3,133 (7.6%)
132,059 (8.7%)
6,102 (6.7%)
0.08
Unmatched
Optum
MarketScan
Medicare
POOLED
Table 1: Saxagliptin vs 2nd Generation Sulfonylureas

Hypoglycemia ; n (%)
8,609 (2.6%)
520 (2.5%)
11,572 (3.3%)
710 (2.4%)
24,098 (2.9%)
1,309 (3.2%)
44,279 (2.9%)
2,539 (2.8%)
0.01
Hyperglycemia; n (%)
14,232 (4.4%)
915 (4.4%)
10,618 (3.0%)
934 (3.2%)
40,740 (4.9%)
1,907 (4.6%)
65,590 (4.3%)
3,756 (4.1%)
0.01
Disorders of fluid electrolyte and acid-base balance; n (%)
27,078 (8.3%)
1,202 (5.8%)
20,401 (5.8%)
1,090 (3.7%)
87,411 (10.5%)
3,443 (8.4%)
134,890 (8.9%)
5,735 (6.3%)
0.10
Diabetic ketoacidosis; n (%)
1,479 (0.5%)
80 (0.4%)
1,620 (0.5%)
97 (0.3%)
3,796 (0.5%)
185 (0.4%)
6,895 (0.5%)
362 (0.4%)
0.01
Hyperosmolar hyperglycemic nonketotic syndrome (HONK
1,713 (0.5%)
98 (0.5%)
1,402 (0.4%)
88 (0.3%)
4,210 (0.5%)
190 (0.5%)
7,325 (0.5%)
376 (0.4%)
0.01
Diabetes with peripheral circulatory disorders with ICD-10
22,010 (6.7%)
1,121 (5.4%)
12,150 (3.4%)
836 (2.9%)
61,626 (7.4%)
2,985 (7.3%)
95,786 (6.3%)
4,942 (5.4%)
0.04
Diabetic Foot; n (%)
7,372 (2.3%)
325 (1.6%)
7,747 (2.2%)
424 (1.5%)
24,279 (2.9%)
1,019 (2.5%)
39,398 (2.6%)
1,768 (1.9%)
0.05
Gangrene ; n (%)
948 (0.3%)
38 (0.2%)
1,009 (0.3%)
41 (0.1%)
2,368 (0.3%)
65 (0.2%)
4,325 (0.3%)
144 (0.2%)
0.02
Lower extremity amputation; n (%)
2,039 (0.6%)
72 (0.3%)
1,321 (0.4%)
53 (0.2%)
5,746 (0.7%)
177 (0.4%)
9,106 (0.6%)
302 (0.3%)
0.04
Osteomyelitis; n (%)
2,044 (0.6%)
90 (0.4%)
2,207 (0.6%)
123 (0.4%)
5,461 (0.7%)
192 (0.5%)
9,712 (0.6%)
405 (0.4%)
0.03
Skin infections ; n (%)
18,023 (5.5%)
972 (4.7%)
19,814 (5.6%)
1,383 (4.7%)
58,702 (7.0%)
2,771 (6.7%)
96,539 (6.4%)
5,126 (5.6%)
0.03
Erectile dysfunction; n (%)
9,449 (2.9%)
765 (3.7%)
8,064 (2.3%)
706 (2.4%)
18,682 (2.2%)
1,044 (2.5%)
36,195 (2.4%)
2,515 (2.8%)
-0.03
Diabetes with unspecified complication; n (%)
14,017 (4.3%)
812 (3.9%)
10,738 (3.0%)
799 (2.7%)
35,652 (4.3%)
1,619 (3.9%)
60,407 (4.0%)
3,230 (3.5%)
0.03
Diabetes mellitus without mention of complications; n (%)
292,730 (89.7%)
19,178 (92.3%)
332,349 (93.8%)
28,174 (96.6%)
787,651 (94.5%)
39,585 (96.2%)
1,412,730 (93.3%)
86,937 (95.4%)
-0.09
Hypertension: 1 inpatient or 2 outpatient claims within 36
265,847 (81.5%)
16,982 (81.7%)
231,281 (65.3%)
19,548 (67.0%)
738,732 (88.6%)
36,794 (89.4%)
1,235,860 (81.6%)
73,324 (80.5%)
0.03
Hyperlipidemia ; n (%)
232,236 (71.2%)
16,351 (78.7%)
197,940 (55.9%)
18,164 (62.3%)
622,378 (74.6%)
33,571 (81.6%)
1,052,554 (69.5%)
68,086 (74.8%)
-0.12
Edema; n (%)
21,485 (6.6%)
1,155 (5.6%)
15,660 (4.4%)
1,142 (3.9%)
79,196 (9.5%)
3,623 (8.8%)
116,341 (7.7%)
5,920 (6.5%)
0.05
Renal Dysfunction (non-diabetic) ; n (%)
70,481 (21.6%)
3,338 (16.1%)
43,795 (12.4%)
2,667 (9.1%)
188,756 (22.6%)
8,462 (20.6%)
303,032 (20.0%)
14,467 (15.9%)
0.11
Occurrence of acute renal disease ; n (%)
12,784 (3.9%)
473 (2.3%)
10,177 (2.9%)
435 (1.5%)
39,490 (4.7%)
1,234 (3.0%)
62,451 (4.1%)
2,142 (2.4%)
0.10
Occurrence of chronic renal insufficiency; n (%)
56,143 (17.2%)
2,604 (12.5%)
29,119 (8.2%)
1,715 (5.9%)
147,896 (17.7%)
6,643 (16.1%)
233,158 (15.4%)
10,962 (12.0%)
0.10
Chronic kidney disease ; n (%)
53,648 (16.4%)
2,483 (11.9%)
27,764 (7.8%)
1,645 (5.6%)
139,695 (16.8%)
6,214 (15.1%)
221,107 (14.6%)
10,342 (11.4%)
0.10
CKD Stage 3-4; n (%)
35,821 (11.0%)
1,590 (7.7%)
17,504 (4.9%)
994 (3.4%)
94,805 (11.4%)
4,042 (9.8%)
148,130 (9.8%)
6,626 (7.3%)
0.09
Occurrence of hypertensive nephropathy; n (%)
24,104 (7.4%)
1,008 (4.9%)
11,427 (3.2%)
636 (2.2%)
66,301 (8.0%)
2,658 (6.5%)
101,832 (6.7%)
4,302 (4.7%)
0.09
Occurrence of miscellaneous renal insufficiency ; n (%)
19,938 (6.1%)
1,040 (5.0%)
14,640 (4.1%)
974 (3.3%)
65,967 (7.9%)
3,095 (7.5%)
100,545 (6.6%)
5,109 (5.6%)
0.04
Glaucoma or cataracts ; n (%)
65,950 (20.2%)
3,870 (18.6%)
55,781 (15.7%)
4,474 (15.3%)
215,464 (25.8%)
11,810 (28.7%)
337,195 (22.3%)
20,154 (22.1%)
0.00
Cellulitis or abscess of toe; n (%)
3,999 (1.2%)
184 (0.9%)
3,342 (0.9%)
184 (0.6%)
10,892 (1.3%)
352 (0.9%)
18,233 (1.2%)
720 (0.8%)
0.04
Foot ulcer; n (%)
7,328 (2.2%)
320 (1.5%)
7,845 (2.2%)
438 (1.5%)
24,448 (2.9%)
1,031 (2.5%)
39,621 (2.6%)
1,789 (2.0%)
0.04
Bladder stones; n (%)
514 (0.2%)
33 (0.2%)
456 (0.1%)
33 (0.1%)
1,745 (0.2%)
75 (0.2%)
2,715 (0.2%)
141 (0.2%)
0.00
Kidney stones; n (%)
7,301 (2.2%)
502 (2.4%)
7,485 (2.1%)
627 (2.2%)
22,828 (2.7%)
1,199 (2.9%)
37,614 (2.5%)
2,328 (2.6%)
-0.01
Urinary tract infections (UTIs); n (%)
31,174 (9.6%)
1,703 (8.2%)
22,900 (6.5%)
1,726 (5.9%)
121,013 (14.5%)
6,278 (15.3%)
175,087 (11.6%)
9,707 (10.7%)
0.03
Dipstick urinalysis; n (%)
112,162 (34.4%)
7,907 (38.1%)
100,855 (28.5%)
9,925 (34.0%)
333,745 (40.0%)
18,914 (46.0%)
546,762 (36.1%)
36,746 (40.3%)
-0.09
Non-dipstick urinalysis; n (%)
122,036 (37.4%)
8,383 (40.3%)
95,471 (27.0%)
9,302 (31.9%)
302,108 (36.2%)
16,602 (40.4%)
519,615 (34.3%)
34,287 (37.6%)
-0.07
Urine function test; n (%)
8,516 (2.6%)
522 (2.5%)
9,123 (2.6%)
798 (2.7%)
30,598 (3.7%)
1,710 (4.2%)
48,237 (3.2%)
3,030 (3.3%)
-0.01
Cytology; n (%)
3,963 (1.2%)
221 (1.1%)
5,092 (1.4%)
393 (1.3%)
13,903 (1.7%)
757 (1.8%)
22,958 (1.5%)
1,371 (1.5%)
0.00
Cystos; n (%)
5,503 (1.7%)
351 (1.7%)
6,722 (1.9%)
535 (1.8%)
19,356 (2.3%)
979 (2.4%)
31,581 (2.1%)
1,865 (2.0%)
0.01
Other Covariates
Liver disease; n (%)
15,381 (4.7%)
1,008 (4.9%)
13,265 (3.7%)
952 (3.3%)
40,486 (4.9%)
2,120 (5.2%)
69,132 (4.6%)
4,080 (4.5%)
0.00
Osteoarthritis; n (%)
49,801 (15.3%)
2,939 (14.1%)
39,609 (11.2%)
3,067 (10.5%)
183,282 (22.0%)
9,595 (23.3%)
272,692 (18.0%)
15,601 (17.1%)
0.02
Other arthritis, arthropathies and musculoskeletal pain; n (
109,875 (33.7%)
6,759 (32.5%)
103,014 (29.1%)
8,257 (28.3%)
361,926 (43.4%)
18,292 (44.5%)
574,815 (38.0%)
33,308 (36.6%)
0.03
Dorsopathies; n (%)
66,258 (20.3%)
4,112 (19.8%)
59,248 (16.7%)
4,994 (17.1%)
213,504 (25.6%)
11,236 (27.3%)
339,010 (22.4%)
20,342 (22.3%)
0.00
Fractures; n (%)
10,142 (3.1%)
464 (2.2%)
9,882 (2.8%)
624 (2.1%)
35,412 (4.2%)
1,478 (3.6%)
55,436 (3.7%)
2,566 (2.8%)
0.05
Falls ; n (%)
11,108 (3.4%)
421 (2.0%)
3,800 (1.1%)
172 (0.6%)
39,560 (4.7%)
1,361 (3.3%)
54,468 (3.6%)
1,954 (2.1%)
0.09
Osteoporosis; n (%)
16,292 (5.0%)
1,166 (5.6%)
11,172 (3.2%)
1,105 (3.8%)
61,430 (7.4%)
4,453 (10.8%)
88,894 (5.9%)
6,724 (7.4%)
-0.06
Hyperthyroidism; n (%)
1,991 (0.6%)
142 (0.7%)
1,498 (0.4%)
145 (0.5%)
7,561 (0.9%)
456 (1.1%)
11,050 (0.7%)
743 (0.8%)
-0.01
Hypothyroidism ; n (%)
46,694 (14.3%)
3,122 (15.0%)
31,244 (8.8%)
2,932 (10.1%)
125,308 (15.0%)
8,092 (19.7%)
203,246 (13.4%)
14,146 (15.5%)
-0.06
Other disorders of thyroid gland ; n (%)
9,131 (2.8%)
731 (3.5%)
7,621 (2.2%)
889 (3.0%)
30,404 (3.6%)
2,249 (5.5%)
47,156 (3.1%)
3,869 (4.2%)
-0.06
Depression; n (%)
25,425 (7.8%)
1,395 (6.7%)
20,171 (5.7%)
1,455 (5.0%)
90,154 (10.8%)
4,150 (10.1%)
135,750 (9.0%)
7,000 (7.7%)
0.05
Anxiety; n (%)
20,439 (6.3%)
1,110 (5.3%)
13,227 (3.7%)
976 (3.3%)
69,211 (8.3%)
3,190 (7.8%)
102,877 (6.8%)
5,276 (5.8%)
0.04
Sleep_Disorder; n (%)
22,256 (6.8%)
1,819 (8.8%)
29,227 (8.3%)
2,945 (10.1%)
65,850 (7.9%)
3,795 (9.2%)
117,333 (7.7%)
8,559 (9.4%)
-0.06
Dementia; n (%)
14,761 (4.5%)
513 (2.5%)
9,793 (2.8%)
417 (1.4%)
70,951 (8.5%)
2,659 (6.5%)
95,505 (6.3%)
3,589 (3.9%)
0.11
Delirium; n (%)
4,546 (1.4%)
127 (0.6%)
3,729 (1.1%)
136 (0.5%)
19,145 (2.3%)
577 (1.4%)
27,420 (1.8%)
840 (0.9%)
0.08
Psychosis; n (%)
3,765 (1.2%)
125 (0.6%)
2,978 (0.8%)
139 (0.5%)
19,739 (2.4%)
696 (1.7%)
26,482 (1.7%)
960 (1.1%)
0.05
Obesity; n (%)
40,498 (12.4%)
2,590 (12.5%)
25,265 (7.1%)
1,801 (6.2%)
85,113 (10.2%)
4,257 (10.3%)
150,876 (10.0%)
8,648 (9.5%)
0.02
Overweight; n (%)
13,422 (4.1%)
748 (3.6%)
4,458 (1.3%)
279 (1.0%)
24,959 (3.0%)
1,164 (2.8%)
42,839 (2.8%)
2,191 (2.4%)
0.03
Smoking; n (%)
33,167 (10.2%)
1,667 (8.0%)
17,912 (5.1%)
1,207 (4.1%)
107,772 (12.9%)
4,199 (10.2%)
158,851 (10.5%)
7,073 (7.8%)
0.09
Alcohol abuse or dependence; n (%)
3,462 (1.1%)
152 (0.7%)
2,699 (0.8%)
134 (0.5%)
7,115 (0.9%)
249 (0.6%)
13,276 (0.9%)
535 (0.6%)
0.03
Drug abuse or dependence; n (%)
3,665 (1.1%)
169 (0.8%)
1,731 (0.5%)
101 (0.3%)
7,330 (0.9%)
281 (0.7%)
12,726 (0.8%)
551 (0.6%)
0.02
COPD; n (%)
31,399 (9.6%)
1,481 (7.1%)
23,290 (6.6%)
1,501 (5.1%)
100,010 (12.0%)
4,618 (11.2%)
154,699 (10.2%)
7,600 (8.3%)
0.07
Asthma; n (%)
15,300 (4.7%)
1,013 (4.9%)
13,235 (3.7%)
1,110 (3.8%)
47,155 (5.7%)
2,619 (6.4%)
75,690 (5.0%)
4,742 (5.2%)
-0.01
Obstructive sleep apnea; n (%)
22,004 (6.7%)
1,612 (7.8%)
25,186 (7.1%)
2,287 (7.8%)
46,520 (5.6%)
2,191 (5.3%)
93,710 (6.2%)
6,090 (6.7%)
-0.02
Table 1: Saxagliptin vs 2nd Generation Sulfonylureas

Pneumonia; n (%)
10,170 (3.1%)
378 (1.8%)
10,127 (2.9%)
466 (1.6%)
34,226 (4.1%)
1,258 (3.1%)
54,523 (3.6%)
2,102 (2.3%)
0.08
Imaging; n (%)
538 (0.2%)
19 (0.1%)
348 (0.1%)
17 (0.1%)
1,552 (0.2%)
51 (0.1%)
2,438 (0.2%)
87 (0.1%)
0.03
Diabetes Medications
DM Medications - AGIs; n (%)
985 (0.3%)
65 (0.3%)
1,078 (0.3%)
80 (0.3%)
2,837 (0.3%)
193 (0.5%)
4,900 (0.3%)
338 (0.4%)
-0.02
DM Medications - Glitazones; n (%)
27,778 (8.5%)
2,623 (12.6%)
41,989 (11.9%)
5,550 (19.0%)
52,109 (6.2%)
4,431 (10.8%)
121,876 (8.0%)
12,604 (13.8%)
-0.19
DM Medications - GLP-1 RA; n (%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
#VALUE!
#VALUE!
#VALUE!
DM Medications - Insulin; n (%)
41,105 (12.6%)
3,173 (15.3%)
44,462 (12.6%)
3,879 (13.3%)
128,124 (15.4%)
7,653 (18.6%)
213,691 (14.1%)
14,705 (16.1%)
-0.06
DM Medications - Meglitinides; n (%)
2,106 (0.6%)
338 (1.6%)
3,358 (0.9%)
778 (2.7%)
8,523 (1.0%)
1,131 (2.7%)
13,987 (0.9%)
2,247 (2.5%)
-0.12
DM Medications - Metformin; n (%)
207,824 (63.7%)
14,677 (70.6%)
226,946 (64.1%)
21,126 (72.5%)
513,950 (61.6%)
27,402 (66.6%)
948,720 (62.7%)
63,205 (69.4%)
-0.14
Concomitant initiation or current use of SGLT2i; n (%)
3,977 (1.2%)
540 (2.6%)
3,386 (1.0%)
349 (1.2%)
6,088 (0.7%)
516 (1.3%)
13,451 (0.9%)
1,405 (1.5%)
-0.06
Concomitant initiation or current use of AGIs; n (%)
723 (0.2%)
45 (0.2%)
806 (0.2%)
49 (0.2%)
2,021 (0.2%)
125 (0.3%)
3,550 (0.2%)
219 (0.2%)
0.00
Concomitant initiation or current use of Glitazones; n (%)
20,847 (6.4%)
1,496 (7.2%)
32,237 (9.1%)
3,195 (11.0%)
39,728 (4.8%)
2,670 (6.5%)
92,812 (6.1%)
7,361 (8.1%)
-0.08
Concomitant initiation or current use of GLP-1 RA; n (%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
#VALUE!
#VALUE!
#VALUE!
Concomitant initiation or current use of Insulin; n (%)
28,494 (8.7%)
2,341 (11.3%)
32,172 (9.1%)
2,912 (10.0%)
90,757 (10.9%)
5,821 (14.1%)
151,423 (10.0%)
11,074 (12.2%)
-0.07
Concomitant initiation or current use of Meglitinides; n (%
1,207 (0.4%)
240 (1.2%)
2,091 (0.6%)
562 (1.9%)
5,382 (0.6%)
801 (1.9%)
8,680 (0.6%)
1,603 (1.8%)
-0.11
Concomitant initiation or current use of Metformin; n (%)
176,567 (54.1%)
12,740 (61.3%)
193,813 (54.7%)
18,432 (63.2%)
434,419 (52.1%)
23,283 (56.6%)
804,799 (53.1%)
54,455 (59.8%)
-0.14
Past use of SGLT2i; n (%)
1,845 (0.6%)
234 (1.1%)
1,223 (0.3%)
119 (0.4%)
3,419 (0.4%)
197 (0.5%)
6,487 (0.4%)
550 (0.6%)
-0.03
Past use of AGIs; n (%)
262 (0.1%)
20 (0.1%)
272 (0.1%)
31 (0.1%)
816 (0.1%)
68 (0.2%)
1,350 (0.1%)
119 (0.1%)
0.00
Past use of Glitazones; n (%)
6,931 (2.1%)
1,127 (5.4%)
9,754 (2.8%)
2,355 (8.1%)
12,381 (1.5%)
1,761 (4.3%)
29,066 (1.9%)
5,243 (5.8%)
-0.20
Past use of GLP-1 RA; n (%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
#VALUE!
000 (0.0%)
#VALUE!
Past use of Insulin; n (%)
12,612 (3.9%)
832 (4.0%)
12,290 (3.5%)
967 (3.3%)
37,375 (4.5%)
1,832 (4.5%)
62,277 (4.1%)
3,631 (4.0%)
0.01
Past use of Meglitinides; n (%)
899 (0.3%)
98 (0.5%)
1,267 (0.4%)
216 (0.7%)
3,141 (0.4%)
330 (0.8%)
5,307 (0.4%)
644 (0.7%)
-0.04
Past use of metformin (final); n (%)
31,257 (9.6%)
1,937 (9.3%)
33,134 (9.4%)
2,694 (9.2%)
79,531 (9.5%)
4,119 (10.0%)
143,922 (9.5%)
8,750 (9.6%)
0.00
Other Medications
Use of ACE inhibitors; n (%)
155,292 (47.6%)
8,589 (41.3%)
168,841 (47.7%)
12,185 (41.8%)
380,058 (45.6%)
16,298 (39.6%)
704,191 (46.5%)
37,072 (40.7%)
0.12
Use of ARBs; n (%)
74,753 (22.9%)
6,018 (29.0%)
85,503 (24.1%)
9,060 (31.1%)
213,647 (25.6%)
13,949 (33.9%)
373,903 (24.7%)
29,027 (31.9%)
-0.16
Use of Loop Diuretics ; n (%)
45,732 (14.0%)
2,095 (10.1%)
47,287 (13.3%)
2,970 (10.2%)
163,097 (19.6%)
7,190 (17.5%)
256,116 (16.9%)
12,255 (13.5%)
0.09
Use of other diuretics; n (%)
9,584 (2.9%)
491 (2.4%)
10,328 (2.9%)
707 (2.4%)
30,836 (3.7%)
1,357 (3.3%)
50,748 (3.4%)
2,555 (2.8%)
0.03
Use of nitrates-United; n (%)
19,150 (5.9%)
970 (4.7%)
22,344 (6.3%)
1,429 (4.9%)
67,077 (8.0%)
3,287 (8.0%)
108,571 (7.2%)
5,686 (6.2%)
0.04
Use of other hypertension drugs; n (%)
25,970 (8.0%)
1,250 (6.0%)
26,097 (7.4%)
1,535 (5.3%)
75,683 (9.1%)
3,334 (8.1%)
127,750 (8.4%)
6,119 (6.7%)
0.06
Use of digoxin; n (%)
7,924 (2.4%)
368 (1.8%)
9,532 (2.7%)
605 (2.1%)
30,623 (3.7%)
1,512 (3.7%)
48,079 (3.2%)
2,485 (2.7%)
0.03
Use of Anti-arrhythmics; n (%)
5,069 (1.6%)
211 (1.0%)
6,091 (1.7%)
348 (1.2%)
19,073 (2.3%)
819 (2.0%)
30,233 (2.0%)
1,378 (1.5%)
0.04
Use of COPD/asthma meds; n (%)
40,979 (12.6%)
2,796 (13.5%)
46,482 (13.1%)
4,170 (14.3%)
129,633 (15.5%)
7,675 (18.7%)
217,094 (14.3%)
14,641 (16.1%)
-0.05
Use of statins; n (%)
206,872 (63.4%)
13,609 (65.5%)
220,717 (62.3%)
18,979 (65.1%)
541,625 (65.0%)
28,292 (68.8%)
969,214 (64.0%)
60,880 (66.8%)
-0.06
Use of other lipid-lowering drugs; n (%)
34,054 (10.4%)
2,947 (14.2%)
47,664 (13.5%)
4,901 (16.8%)
90,399 (10.8%)
5,974 (14.5%)
172,117 (11.4%)
13,822 (15.2%)
-0.11
Use of antiplatelet agents; n (%)
39,164 (12.0%)
2,606 (12.5%)
49,626 (14.0%)
4,089 (14.0%)
120,312 (14.4%)
6,953 (16.9%)
209,102 (13.8%)
13,648 (15.0%)
-0.03
Use of oral anticoagulants (Dabigatran, Rivaroxaban, Apixa
22,175 (6.8%)
1,078 (5.2%)
23,822 (6.7%)
1,445 (5.0%)
84,094 (10.1%)
3,537 (8.6%)
130,091 (8.6%)
6,060 (6.7%)
0.07
Use of heparin and other low-molecular weight heparins; n
1,612 (0.5%)
90 (0.4%)
105 (0.0%)
1 (0.0%)
4,807 (0.6%)
169 (0.4%)
6,524 (0.4%)
260 (0.3%)
0.02
Use of NSAIDs; n (%)
45,323 (13.9%)
3,100 (14.9%)
48,638 (13.7%)
4,344 (14.9%)
125,605 (15.1%)
7,302 (17.7%)
219,566 (14.5%)
14,746 (16.2%)
-0.05
Use of oral corticosteroids; n (%)
43,644 (13.4%)
2,665 (12.8%)
46,469 (13.1%)
3,678 (12.6%)
134,781 (16.2%)
6,572 (16.0%)
224,894 (14.9%)
12,915 (14.2%)
0.02
Use of bisphosphonate (United); n (%)
8,508 (2.6%)
603 (2.9%)
7,182 (2.0%)
637 (2.2%)
25,961 (3.1%)
1,971 (4.8%)
41,651 (2.8%)
3,211 (3.5%)
-0.04
Use of opioids; n (%)
78,095 (23.9%)
4,736 (22.8%)
88,854 (25.1%)
6,978 (23.9%)
219,576 (26.3%)
10,565 (25.7%)
386,525 (25.5%)
22,279 (24.5%)
0.02
Use of antidepressants; n (%)
67,097 (20.6%)
4,035 (19.4%)
69,354 (19.6%)
5,621 (19.3%)
205,107 (24.6%)
10,384 (25.2%)
341,558 (22.6%)
20,040 (22.0%)
0.01
Use of antipsychotics; n (%)
7,040 (2.2%)
369 (1.8%)
6,306 (1.8%)
432 (1.5%)
29,618 (3.6%)
1,457 (3.5%)
42,964 (2.8%)
2,258 (2.5%)
0.02
Use of anticonvulsants; n (%)
44,305 (13.6%)
2,376 (11.4%)
37,580 (10.6%)
2,730 (9.4%)
135,780 (16.3%)
6,460 (15.7%)
217,665 (14.4%)
11,566 (12.7%)
0.05
Use of lithium; n (%)
406 (0.1%)
23 (0.1%)
511 (0.1%)
26 (0.1%)
1,154 (0.1%)
44 (0.1%)
2,071 (0.1%)
093 (0.1%)
0.00
Use of Benzos; n (%)
25,438 (7.8%)
1,649 (7.9%)
36,367 (10.3%)
2,964 (10.2%)
81,585 (9.8%)
3,787 (9.2%)
143,390 (9.5%)
8,400 (9.2%)
0.01
Use of anxiolytics/hypnotics; n (%)
17,416 (5.3%)
1,301 (6.3%)
21,131 (6.0%)
1,988 (6.8%)
51,549 (6.2%)
3,336 (8.1%)
90,096 (5.9%)
6,625 (7.3%)
-0.06
Use of dementia meds; n (%)
8,507 (2.6%)
361 (1.7%)
7,359 (2.1%)
365 (1.3%)
42,615 (5.1%)
2,350 (5.7%)
58,481 (3.9%)
3,076 (3.4%)
0.03
Use of antiparkinsonian meds; n (%)
7,238 (2.2%)
410 (2.0%)
7,186 (2.0%)
556 (1.9%)
27,741 (3.3%)
1,332 (3.2%)
42,165 (2.8%)
2,298 (2.5%)
0.02
Any use of pramlintide; n (%)
32 (0.0%)
11 (0.1%)
139 (0.0%)
38 (0.1%)
64 (0.0%)
12 (0.0%)
235 (0.0%)
061 (0.1%)
-0.04
Any use of 1st generation sulfonylureas; n (%)
133 (0.0%)
5 (0.0%)
465 (0.1%)
8 (0.0%)
538 (0.1%)
19 (0.0%)
1,136 (0.1%)
032 (0.0%)
0.00
Entresto (sacubitril/valsartan); n (%)
250 (0.1%)
16 (0.1%)
58 (0.0%)
1 (0.0%)
320 (0.0%)
11 (0.0%)
628 (0.0%)
028 (0.0%)
0.00
Initiation as monotherapy ; n (%)
58,625 (18.0%)
4,352 (20.9%)
57,540 (16.2%)
5,432 (18.6%)
121,960 (14.6%)
6,427 (15.6%)
238,125 (15.7%)
16,211 (17.8%)
-0.06
Labs
                                       680,475                                           49,938 
Lab values- HbA1c (%) ; n (%)
100,016 (30.7%)
7,392 (35.6%)
21,446 (6.1%)
1,595 (5.5%)
N/A
N/A
121,462 (17.8%)
8,987 (18.0%)
-0.01
Lab values- HbA1c (%) (within 3 months) ; n (%)
77,689 (23.8%)
5,930 (28.5%)
16,948 (4.8%)
1,266 (4.3%)
N/A
N/A
94,637 (13.9%)
7,196 (14.4%)
-0.01
Lab values- HbA1c (%) (within 6 months) ; n (%)
100,016 (30.7%)
7,392 (35.6%)
21,446 (6.1%)
1,595 (5.5%)
N/A
N/A
121,462 (17.8%)
8,987 (18.0%)
-0.01
Lab values- BNP; n (%)
1,893 (0.6%)
97 (0.5%)
259 (0.1%)
19 (0.1%)
N/A
N/A
2,152 (0.3%)
116 (0.2%)
0.02
Table 1: Saxagliptin vs 2nd Generation Sulfonylureas

Lab values- BNP (within 3 months); n (%)
1,190 (0.4%)
60 (0.3%)
174 (0.0%)
10 (0.0%)
N/A
N/A
1,364 (0.2%)
070 (0.1%)
0.03
Lab values- BNP (within 6 months); n (%)
1,893 (0.6%)
97 (0.5%)
259 (0.1%)
19 (0.1%)
N/A
N/A
2,152 (0.3%)
116 (0.2%)
0.02
Lab values- BUN (mg/dl); n (%)
102,893 (31.5%)
7,740 (37.2%)
15,379 (4.3%)
1,670 (5.7%)
N/A
N/A
118,272 (17.4%)
9,410 (18.8%)
-0.04
Lab values- BUN (mg/dl) (within 3 months); n (%)
79,292 (24.3%)
6,146 (29.6%)
11,735 (3.3%)
1,300 (4.5%)
N/A
N/A
91,027 (13.4%)
7,446 (14.9%)
-0.04
Lab values- BUN (mg/dl) (within 6 months); n (%)
102,893 (31.5%)
7,740 (37.2%)
15,379 (4.3%)
1,670 (5.7%)
N/A
N/A
118,272 (17.4%)
9,410 (18.8%)
-0.04
Lab values- Creatinine (mg/dl) ; n (%)
105,172 (32.2%)
7,907 (38.1%)
16,016 (4.5%)
1,728 (5.9%)
N/A
N/A
121,188 (17.8%)
9,635 (19.3%)
-0.04
Lab values- Creatinine (mg/dl) (within 3 months) ; n (%)
81,025 (24.8%)
6,286 (30.3%)
12,246 (3.5%)
1,342 (4.6%)
N/A
N/A
93,271 (13.7%)
7,628 (15.3%)
-0.05
Lab values- Creatinine (mg/dl) (within 6 months) ; n (%)
105,172 (32.2%)
7,907 (38.1%)
16,016 (4.5%)
1,728 (5.9%)
N/A
N/A
121,188 (17.8%)
9,635 (19.3%)
-0.04
Lab values- HDL level (mg/dl); n (%)
84,638 (25.9%)
6,626 (31.9%)
18,060 (5.1%)
1,484 (5.1%)
N/A
N/A
102,698 (15.1%)
8,110 (16.2%)
-0.03
Lab values- HDL level (mg/dl) (within 3 months); n (%)
61,783 (18.9%)
5,027 (24.2%)
13,316 (3.8%)
1,117 (3.8%)
N/A
N/A
75,099 (11.0%)
6,144 (12.3%)
-0.04
Lab values- HDL level (mg/dl) (within 6 months); n (%)
84,638 (25.9%)
6,626 (31.9%)
18,060 (5.1%)
1,484 (5.1%)
N/A
N/A
102,698 (15.1%)
8,110 (16.2%)
-0.03
Lab values- LDL level (mg/dl) ; n (%)
87,126 (26.7%)
6,698 (32.2%)
19,684 (5.6%)
1,508 (5.2%)
N/A
N/A
106,810 (15.7%)
8,206 (16.4%)
-0.02
Lab values- LDL level (mg/dl) (within 3 months) ; n (%)
63,562 (19.5%)
5,094 (24.5%)
14,509 (4.1%)
1,133 (3.9%)
N/A
N/A
78,071 (11.5%)
6,227 (12.5%)
-0.03
Lab values- LDL level (mg/dl) (within 6 months) ; n (%)
87,126 (26.7%)
6,698 (32.2%)
19,684 (5.6%)
1,508 (5.2%)
N/A
N/A
106,810 (15.7%)
8,206 (16.4%)
-0.02
Lab values- NT-proBNP; n (%)
260 (0.1%)
18 (0.1%)
20 (0.0%)
1 (0.0%)
N/A
N/A
280 (0.0%)
19 (0.0%)
#DIV/0!
Lab values- NT-proBNP (within 3 months); n (%)
161 (0.0%)
13 (0.1%)
12 (0.0%)
1 (0.0%)
N/A
N/A
173 (0.0%)
14 (0.0%)
-
Lab values- NT-proBNP (within 6 months); n (%)
260 (0.1%)
18 (0.1%)
20 (0.0%)
1 (0.0%)
N/A
N/A
280 (0.0%)
19 (0.0%)
-
Lab values- Total cholesterol (mg/dl) ; n (%)
85,810 (26.3%)
6,733 (32.4%)
18,318 (5.2%)
1,521 (5.2%)
N/A
N/A
104,128 (15.3%)
8,254 (16.5%)
-0.03
Lab values- Total cholesterol (mg/dl) (within 3 months) ; n (
62,648 (19.2%)
5,117 (24.6%)
13,460 (3.8%)
1,147 (3.9%)
N/A
N/A
76,108 (11.2%)
6,264 (12.5%)
-0.04
Lab values- Total cholesterol (mg/dl) (within 6 months) ; n (
85,810 (26.3%)
6,733 (32.4%)
18,318 (5.2%)
1,521 (5.2%)
N/A
N/A
104,128 (15.3%)
8,254 (16.5%)
-0.03
Lab values- Triglyceride level (mg/dl); n (%)
85,006 (26.1%)
6,707 (32.3%)
17,930 (5.1%)
1,485 (5.1%)
N/A
N/A
102,936 (15.1%)
8,192 (16.4%)
-0.04
Lab values- Triglyceride level (mg/dl) (within 3 months); n (%
62,117 (19.0%)
5,102 (24.6%)
13,198 (3.7%)
1,118 (3.8%)
N/A
N/A
75,315 (11.1%)
6,220 (12.5%)
-0.04
Lab values- Triglyceride level (mg/dl) (within 6 months); n (%
85,006 (26.1%)
6,707 (32.3%)
17,930 (5.1%)
1,485 (5.1%)
N/A
N/A
102,936 (15.1%)
8,192 (16.4%)
-0.04
Lab result number- HbA1c (%) mean (only 2 to 20 included)
99,508
                                         
7,371
                                            
16,692
                                         
1,504
                                            
N/A
N/A                                        116,200                                              8,875 
...mean (sd)
8.02 (1.79)
7.95 (1.71)
8.15 (1.89)
8.03 (1.81)
N/A
N/A
8.04 (1.80)
7.96 (1.73)
0.05
...median [IQR]
7.60 [6.80, 8.80]
7.50 [6.80, 8.65]
7.65 [6.90, 9.00]
7.50 [6.80, 8.70]
N/A
N/A
7.61 (1.80)
7.50 (1.73)
0.06
...Missing; n (%)
226,748 (69.5%)
13,408 (64.5%)
337,527 (95.3%)
27,655 (94.8%)
N/A
N/A
564,275 (82.9%)
41,063 (82.2%)
0.02
Lab result number- BNP mean 
1,893
                                            
97
                                                   
259
                                                
19
                                                   
N/A
N/A                                              2,152                                                  116 
...mean (sd)
225.59 (409.79)
152.44 (201.22)
261.61 (540.42)
238.55 (559.75)
N/A
N/A
229.93 (427.68)
166.54 (290.36)
0.17
...median [IQR]
90.90 [34.30, 241.75]
85.00 [32.40, 195.85]
74.00 [26.00, 230.00]
30.00 [17.00, 112.00]
N/A
N/A
#VALUE!
#VALUE!
#VALUE!
...Missing; n (%)
324,363 (99.4%)
20,682 (99.5%)
353,960 (99.9%)
29,140 (99.9%)
N/A
N/A
678,323 (99.7%)
49,822 (99.8%)
-0.02
Lab result number- BUN (mg/dl) mean 
                                       102,893                                              7,740                                           15,379                                              1,670 
N/A
N/A                                        118,272                                              9,410 
...mean (sd)
19.15 (8.38)
18.03 (7.12)
586.28 (9,772.52)
373.82 (7,794.27)
N/A
N/A
92.89 (3523.89)
81.17 (3283.06)
0.00
...median [IQR]
17.00 [14.00, 22.00]
16.50 [13.50, 21.00]
17.00 [14.00, 21.00]
17.00 [13.00, 20.00]
N/A
N/A
#VALUE!
#VALUE!
#VALUE!
...Missing; n (%)
223,363 (68.5%)
13,039 (62.8%)
338,840 (95.7%)
27,489 (94.3%)
N/A
N/A
562,203 (82.6%)
40,528 (81.2%)
0.04
Lab result number- Creatinine (mg/dl) mean (only 0.1 to 15                                        104,570                                              7,870                                           15,098                                              1,683 
N/A
N/A                                        119,668                                              9,553 
...mean (sd)
1.06 (0.42)
1.01 (0.35)
1.03 (0.38)
0.99 (0.33)
N/A
N/A
1.06 (0.42)
1.01 (0.35)
0.13
...median [IQR]
0.97 [0.81, 1.20]
0.95 [0.80, 1.13]
0.97 [0.81, 1.14]
0.93 [0.80, 1.10]
N/A
N/A
0.97 (0.42)
0.95 (0.35)
0.05
...Missing; n (%)
221,686 (67.9%)
12,909 (62.1%)
339,121 (95.7%)
27,476 (94.2%)
N/A
N/A
560,807 (82.4%)
40,385 (80.9%)
0.04
Lab result number- HDL level (mg/dl) mean (only =<5000 in                                           84,638                                              6,626                                           18,017                                              1,481 
N/A
N/A                                        102,655                                              8,107 
...mean (sd)
46.33 (13.72)
46.38 (13.32)
44.68 (13.73)
45.39 (13.98)
N/A
N/A
46.04 (13.72)
46.20 (13.44)
-0.01
...median [IQR]
44.00 [37.00, 53.50]
44.00 [37.00, 53.00]
43.00 [36.00, 52.00]
44.00 [37.00, 52.50]
N/A
N/A
43.82 (13.72)
44.00 (13.44)
-0.01
...Missing; n (%)
241,618 (74.1%)
14,153 (68.1%)
336,202 (94.9%)
27,678 (94.9%)
N/A
N/A
577,820 (84.9%)
41,831 (83.8%)
0.03
Lab result number- LDL level (mg/dl) mean (only =<5000 inc                                          85,353                                              6,598                                           17,773                                              1,436 
N/A
N/A                                        103,126                                              8,034 
...mean (sd)
88.53 (39.92)
87.43 (38.51)
88.95 (41.17)
89.25 (40.99)
N/A
N/A
88.60 (40.14)
87.76 (38.97)
0.02
...median [IQR]
85.00 [64.00, 111.50]
84.00 [64.00, 109.00]
86.00 [65.00, 112.00]
87.00 [65.00, 112.38]
N/A
N/A
85.17 (40.14)
84.54 (38.97)
0.02
...Missing; n (%)
240,903 (73.8%)
14,181 (68.2%)
336,446 (95.0%)
27,723 (95.1%)
N/A
N/A
577,349 (84.8%)
41,904 (83.9%)
0.02
Lab result number- Total cholesterol (mg/dl) mean (only =<                                           85,752                                              6,730                                           18,262                                              1,515 
N/A
N/A                                        104,014                                              8,245 
...mean (sd)
174.39 (46.55)
172.96 (46.08)
174.81 (49.91)
174.96 (49.83)
N/A
N/A
174.46 (47.16)
173.33 (46.79)
0.02
...median [IQR]
168.00 [143.00, 199.00]
166.00 [143.00, 197.00]
169.50 [144.00, 201.00]
169.50 [145.50, 201.00]
N/A
N/A
168.26 (47.16)
166.64 (46.79)
0.03
...Missing; n (%)
240,504 (73.7%)
14,049 (67.6%)
335,957 (94.8%)
27,644 (94.8%)
N/A
N/A
576,461 (84.7%)
41,693 (83.5%)
0.03
Lab result number- Triglyceride level (mg/dl) mean (only =<                                           85,000                                              6,706                                           17,886                                              1,482 
N/A
N/A                                        102,886                                              8,188 
Table 1: Saxagliptin vs 2nd Generation Sulfonylureas

...mean (sd)
182.88 (149.01)
179.77 (153.27)
191.33 (174.74)
188.19 (193.76)
N/A
N/A
184.35 (153.79)
181.29 (161.36)
0.02
...median [IQR]
150.00 [107.00, 214.33]
147.50 [105.00, 210.00]
153.00 [107.00, 222.00]
150.00 [103.00, 221.00]
N/A
N/A
150.52 (153.79)
147.95 (161.36)
0.02
...Missing; n (%)
241,256 (73.9%)
14,073 (67.7%)
336,333 (95.0%)
27,677 (94.9%)
N/A
N/A
577,589 (84.9%)
41,750 (83.6%)
0.04
Lab result number- Hemoglobin mean (only >0 included)
                                          72,386                                              5,292                                              9,854                                              1,027 
N/A
N/A                                           82,240                                              6,319 
...mean (sd)
13.46 (1.73)
13.72 (1.69)
4,136.65 (181,794.60)
522.41 (8,421.85)
N/A
N/A
507.50 (62926.21)
96.40 (3394.38)
0.01
...median [IQR]
13.50 [12.30, 14.60]
13.80 [12.60, 14.90]
13.80 [12.60, 14.90]
14.00 [12.90, 15.00]
N/A
N/A
#VALUE!
#VALUE!
#VALUE!
...Missing; n (%)
253,870 (77.8%)
15,487 (74.5%)
344,365 (97.2%)
28,132 (96.5%)
N/A
N/A
598,235 (87.9%)
43,619 (87.3%)
0.02
Lab result number- Serum sodium mean (only > 90 and < 19                                        102,168                                              7,735                                           14,001                                              1,597 
N/A
N/A                                        116,169                                              9,332 
...mean (sd)
139.32 (2.84)
139.38 (2.70)
138.77 (2.75)
138.94 (2.61)
N/A
N/A
139.25 (2.83)
139.30 (2.68)
-0.02
...median [IQR]
139.50 [138.00, 141.00]
139.50 [138.00, 141.00]
139.00 [137.00, 140.50]
139.00 [137.50, 141.00]
N/A
N/A
139.44 (2.83)
139.41 (2.68)
0.01
...Missing; n (%)
224,088 (68.7%)
13,044 (62.8%)
340,218 (96.0%)
27,562 (94.5%)
N/A
N/A
564,306 (82.9%)
40,606 (81.3%)
0.04
Lab result number- Albumin mean (only >0 and <=10 includ                                           94,681                                              7,310                                           12,437                                              1,463 
N/A
N/A                                        107,118                                              8,773 
...mean (sd)
4.23 (0.33)
4.28 (0.32)
4.18 (0.57)
4.24 (0.58)
N/A
N/A
4.22 (0.37)
4.27 (0.38)
-0.13
...median [IQR]
4.25 [4.03, 4.45]
4.30 [4.10, 4.50]
4.25 [4.00, 4.50]
4.30 [4.10, 4.50]
N/A
N/A
4.25 (0.37)
4.30 (0.38)
-0.13
...Missing; n (%)
231,575 (71.0%)
13,469 (64.8%)
341,782 (96.5%)
27,696 (95.0%)
N/A
N/A
573,357 (84.3%)
41,165 (82.4%)
0.05
Lab result number- Glucose (fasting or random) mean (only                                        102,043                                              7,747                                           13,741                                              1,522 
N/A
N/A                                        115,784                                              9,269 
...mean (sd)
168.63 (71.80)
163.00 (65.86)
176.14 (76.75)
164.90 (65.90)
N/A
N/A
169.52 (72.41)
163.31 (65.87)
0.09
...median [IQR]
151.00 [122.00, 195.00]
146.00 [120.00, 185.00]
156.00 [125.00, 206.83]
148.00 [121.38, 192.00]
N/A
N/A
151.59 (72.41)
146.33 (65.87)
0.08
...Missing; n (%)
224,213 (68.7%)
13,032 (62.7%)
340,478 (96.1%)
27,637 (94.8%)
N/A
N/A
564,691 (83.0%)
40,669 (81.4%)
0.04
Lab result number- Potassium mean (only 1-7 included)
                                       104,247                                              7,831                                           15,120                                              1,636 
N/A
N/A                                        119,367                                              9,467 
...mean (sd)
4.44 (0.44)
4.40 (0.42)
4.37 (0.44)
4.39 (0.41)
N/A
N/A
4.43 (0.44)
4.40 (0.42)
0.07
...median [IQR]
4.40 [4.15, 4.70]
4.40 [4.10, 4.65]
4.35 [4.10, 4.62]
4.40 [4.10, 4.60]
N/A
N/A
4.39 (0.44)
4.40 (0.42)
-0.02
...Missing; n (%)
222,009 (68.0%)
12,948 (62.3%)
339,099 (95.7%)
27,523 (94.4%)
N/A
N/A
561,108 (82.5%)
40,471 (81.0%)
0.04
Comorbidity Scores
CCI (180 days)- ICD9 and ICD10 
...mean (sd)
2.64 (2.03)
2.24 (1.79)
1.89 (1.77)
1.62 (1.50)
3.05 (2.19)
2.88 (2.07)
2.69 (2.06)
2.33 (1.84)
0.18
...median [IQR]
2.00 [1.00, 4.00]
2.00 [1.00, 3.00]
1.00 [1.00, 3.00]
1.00 [1.00, 2.00]
2.00 [1.00, 4.00]
2.00 [1.00, 4.00]
1.77 (2.06)
1.68 (1.84)
0.05
Frailty Score: Qualitative Version 365 days as Categories, 
...0; n (%)
144,570 (44.3%)
8,405 (40.4%)
130,992 (37.0%)
10,100 (34.6%)
243,493 (29.2%)
8,951 (21.8%)
519,055 (34.3%)
27,456 (30.1%)
0.09
...1 to 2; n (%)
109,279 (33.5%)
7,860 (37.8%)
142,156 (40.1%)
13,184 (45.2%)
280,929 (33.7%)
14,929 (36.3%)
532,364 (35.2%)
35,973 (39.5%)
-0.09
...3 or more; n (%)
72,407 (22.2%)
4,514 (21.7%)
81,071 (22.9%)
5,875 (20.1%)
309,408 (37.1%)
17,264 (42.0%)
462,886 (30.6%)
27,653 (30.4%)
0.00
Frailty Score: Empirical Version 365 days as Categories, 
...< 0.12908; n (%)
79,447 (24.4%)
6,187 (29.8%)
93,169 (26.3%)
8,684 (29.8%)
94,495 (11.3%)
4,810 (11.7%)
267,111 (17.6%)
19,681 (21.6%)
-0.10
...0.12908 - 0.1631167; n (%)
101,582 (31.1%)
6,793 (32.7%)
113,888 (32.2%)
9,961 (34.2%)
194,372 (23.3%)
9,685 (23.5%)
409,842 (27.1%)
26,439 (29.0%)
-0.04
...>= 0.1631167; n (%)
145,227 (44.5%)
7,799 (37.5%)
147,162 (41.5%)
10,514 (36.1%)
544,963 (65.4%)
26,649 (64.8%)
837,352 (55.3%)
44,962 (49.4%)
0.12
Non-Frailty; n (%)
182,262 (55.9%)
11,848 (57.0%)
175,584 (49.6%)
15,199 (52.1%)
37,855 (4.5%)
1,488 (3.6%)
395,701 (26.1%)
28,535 (31.3%)
-0.12
Frailty Score (mean): Qualitative Version 365 days, 
...mean (sd)
1.52 (2.10)
1.49 (1.90)
1.59 (1.95)
1.46 (1.68)
2.34 (2.51)
2.53 (2.36)
1.99 (2.30)
1.95 (2.06)
0.02
...median [IQR]
1.00 [0.00, 2.00]
1.00 [0.00, 2.00]
1.00 [0.00, 2.00]
1.00 [0.00, 2.00]
2.00 [0.00, 4.00]
2.00 [1.00, 4.00]
1.55 (2.30)
1.45 (2.06)
0.05
Frailty Score (mean): Empirical Version 365 days, 
...mean (sd)
0.15 (0.06)
0.15 (0.05)
0.16 (0.05)
0.15 (0.05)
0.20 (0.07)
0.19 (0.07)
0.18 (0.06)
0.17 (0.06)
0.17
...median [IQR]
0.13 [0.10, 0.17]
0.13 [0.11, 0.17]
0.15 [0.12, 0.18]
0.14 [0.12, 0.17]
0.18 [0.15, 0.23]
0.18 [0.15, 0.23]
0.16 (0.06)
0.16 (0.06)
0.00
Healthcare Utilization
Any hospitalization; n (%)
35,287 (10.8%)
1,425 (6.9%)
43,063 (12.2%)
2,073 (7.1%)
115,570 (13.9%)
3,921 (9.5%)
193,920 (12.8%)
7,419 (8.1%)
0.15
Any hospitalization within prior 30 days; n (%)
14,867 (4.6%)
352 (1.7%)
16,930 (4.8%)
428 (1.5%)
42,910 (5.1%)
1,044 (2.5%)
74,707 (4.9%)
1,824 (2.0%)
0.16
Any hospitalization during prior 31-180 days; n (%)
22,672 (6.9%)
1,121 (5.4%)
28,419 (8.0%)
1,706 (5.9%)
80,929 (9.7%)
3,095 (7.5%)
132,020 (8.7%)
5,922 (6.5%)
0.08
Endocrinologist Visit; n (%)
18,976 (5.8%)
1,974 (9.5%)
20,447 (5.8%)
2,685 (9.2%)
64,972 (7.8%)
4,910 (11.9%)
104,395 (6.9%)
9,569 (10.5%)
-0.13
Endocrinologist Visit (30 days prior); n (%)
10,972 (3.4%)
1,271 (6.1%)
12,019 (3.4%)
1,888 (6.5%)
36,189 (4.3%)
3,019 (7.3%)
59,180 (3.9%)
6,178 (6.8%)
-0.13
Endocrinologist Visit (31 to 180 days prior); n (%)
13,157 (4.0%)
1,382 (6.7%)
14,187 (4.0%)
1,815 (6.2%)
48,466 (5.8%)
3,711 (9.0%)
75,810 (5.0%)
6,908 (7.6%)
-0.11
Internal medicine/family medicine visits; n (%)
279,476 (85.7%)
16,015 (77.1%)
290,157 (81.9%)
25,344 (86.9%)
698,850 (83.8%)
34,934 (84.9%)
1,268,483 (83.8%)
76,293 (83.8%)
0.00
Internal medicine/family medicine visits (30 days prior) ; n 
209,246 (64.1%)
11,953 (57.5%)
213,564 (60.3%)
19,663 (67.4%)
497,741 (59.7%)
25,429 (61.8%)
920,551 (60.8%)
57,045 (62.6%)
-0.04
Internal medicine/family medicine visits (31 to 180 days pr
238,305 (73.0%)
13,787 (66.4%)
238,819 (67.4%)
21,573 (74.0%)
601,665 (72.2%)
31,272 (76.0%)
1,078,789 (71.2%)
66,632 (73.2%)
-0.04
Cardiologist visit; n (%)
88,147 (27.0%)
5,475 (26.3%)
77,765 (22.0%)
6,761 (23.2%)
288,718 (34.6%)
14,709 (35.8%)
454,630 (30.0%)
26,945 (29.6%)
0.01
Number of Cardiologist visits (30 days prior); n (%)
34,095 (10.5%)
1,954 (9.4%)
28,267 (8.0%)
2,434 (8.3%)
106,572 (12.8%)
5,200 (12.6%)
168,934 (11.2%)
9,588 (10.5%)
0.02
Number of Cardiologist visits (31 to 180 days prior); n (%)
71,893 (22.0%)
4,633 (22.3%)
64,786 (18.3%)
5,657 (19.4%)
245,011 (29.4%)
12,880 (31.3%)
381,690 (25.2%)
23,170 (25.4%)
0.00
Electrocardiogram ; n (%)
100,694 (30.9%)
6,409 (30.8%)
106,524 (30.1%)
9,248 (31.7%)
297,892 (35.7%)
15,158 (36.8%)
505,110 (33.4%)
30,815 (33.8%)
-0.01
Table 1: Saxagliptin vs 2nd Generation Sulfonylureas

Use of glucose test strips; n (%)
11,797 (3.6%)
853 (4.1%)
12,023 (3.4%)
1,275 (4.4%)
29,191 (3.5%)
1,529 (3.7%)
53,011 (3.5%)
3,657 (4.0%)
-0.03
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 ; n (%)
100,125 (30.7%)
6,035 (29.0%)
104,280 (29.4%)
7,406 (25.4%)
215,694 (25.9%)
9,800 (23.8%)
420,099 (27.7%)
23,241 (25.5%)
0.05
N antidiabetic drugs at index date 
...mean (sd)
1.71 (0.63)
1.84 (0.66)
1.75 (0.65)
1.87 (0.67)
1.69 (0.63)
1.81 (0.66)
1.71 (0.63)
1.84 (0.66)
-0.20
...median [IQR]
2.00 [1.00, 2.00]
2.00 [1.00, 2.00]
2.00 [1.00, 2.00]
2.00 [1.00, 2.00]
2.00 [1.00, 2.00]
2.00 [1.00, 2.00]
2.00 (0.63)
2.00 (0.66)
0.00
number of different/distinct medication prescriptions
...mean (sd)
9.04 (4.55)
9.01 (4.67)
8.91 (4.49)
9.01 (4.53)
9.48 (4.52)
10.14 (5.03)
9.25 (4.52)
9.52 (4.79)
-0.06
...median [IQR]
8.00 [6.00, 12.00]
8.00 [6.00, 12.00]
8.00 [6.00, 11.00]
8.00 [6.00, 11.00]
9.00 [6.00, 12.00] 9.00 [7.00, 13.00]
8.55 (4.52)
8.45 (4.79)
0.02
Number of Hospitalizations
...mean (sd)
0.13 (0.43)
0.08 (0.33)
0.14 (0.43)
0.08 (0.32)
0.18 (0.52)
0.12 (0.42)
0.16 (0.48)
0.10 (0.37)
0.14
...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 (0.48)
0.00 (0.37)
0.00
Number of hospital days
...mean (sd)
0.78 (3.52)
0.44 (2.26)
0.87 (3.92)
0.43 (2.33)
1.16 (4.59)
0.72 (3.58)
1.01 (4.23)
0.56 (2.95)
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 (4.23)
0.00 (2.95)
0.00
Number of Emergency Department (ED) visits 
...mean (sd)
0.42 (1.21)
0.28 (0.89)
0.21 (1.40)
0.11 (1.03)
0.61 (1.48)
0.48 (1.27)
0.48 (1.41)
0.32 (1.12)
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 (1.41)
0.00 (1.12)
0.00
Number of Office visits
...mean (sd)
4.66 (3.91)
4.93 (3.87)
4.65 (4.13)
5.03 (3.99)
5.42 (4.50)
6.30 (4.81)
5.08 (4.29)
5.58 (4.35)
-0.12
...median [IQR]
4.00 [2.00, 6.00]
4.00 [2.00, 6.00]
4.00 [2.00, 6.00]
4.00 [2.00, 7.00]
4.00 [2.00, 7.00]
5.00 [3.00, 8.00]
4.00 (4.29)
4.45 (4.35)
-0.10
Number of Endocrinologist visits
...mean (sd)
0.26 (1.68)
0.49 (2.47)
0.25 (1.62)
0.52 (2.67)
0.43 (2.50)
0.81 (3.84)
0.35 (2.16)
0.64 (3.21)
-0.11
...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 (2.16)
0.00 (3.21)
0.00
Number of internal medicine/family medicine visits
...mean (sd)
9.90 (13.97)
7.91 (12.17)
6.53 (9.66)
7.35 (9.32)
8.17 (10.66)
9.17 (11.81)
8.16 (11.24)
8.30 (11.16)
-0.01
...median [IQR]
6.00 [2.00, 13.00]
5.00 [1.00, 11.00]
4.00 [1.00, 8.00]
5.00 [2.00, 10.00]
5.00 [2.00, 11.00] 6.00 [2.00, 12.00]
4.98 (11.24)
5.45 (11.16)
-0.04
Number of Cardiologist visits
...mean (sd)
1.38 (3.89)
1.35 (3.98)
0.98 (3.06)
1.07 (3.34)
1.85 (4.67)
2.03 (4.87)
1.55 (4.18)
1.57 (4.23)
0.00
...median [IQR]
0.00 [0.00, 1.00]
0.00 [0.00, 1.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 2.00]
0.00 [0.00, 2.00]
0.00 (4.18)
0.00 (4.23)
0.00
Number electrocardiograms received 
...mean (sd)
0.63 (1.46)
0.53 (1.15)
0.55 (1.21)
0.53 (1.08)
0.76 (1.46)
0.73 (1.35)
0.68 (1.41)
0.62 (1.22)
0.05
...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]
0.00 [0.00, 1.00]
0.00 [0.00, 1.00]
0.00 (1.41)
0.00 (1.22)
0.00
Number of HbA1c tests ordered
...mean (sd)
1.14 (0.89)
1.25 (0.87)
0.84 (0.86)
1.03 (0.90)
1.28 (0.88)
1.42 (0.90)
1.15 (0.88)
1.26 (0.89)
-0.12
...median [IQR]
1.00 [1.00, 2.00]
1.00 [1.00, 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 (0.88)
1.00 (0.89)
0.00
Number of glucose tests ordered
...mean (sd)
0.48 (2.98)
0.48 (1.61)
0.36 (1.34)
0.41 (1.05)
0.40 (1.06)
0.51 (1.25)
0.41 (1.72)
0.47 (1.28)
-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, 1.00]
0.00 (1.72)
0.00 (1.28)
0.00
Number of lipid tests ordered
...mean (sd)
0.91 (0.93)
1.09 (1.00)
0.72 (1.13)
0.97 (1.33)
0.93 (0.82)
1.14 (0.90)
0.88 (0.92)
1.07 (1.08)
-0.19
...median [IQR]
1.00 [0.00, 1.00]
1.00 [0.00, 2.00]
0.00 [0.00, 1.00]
1.00 [0.00, 1.00]
1.00 [0.00, 1.00]
1.00 [1.00, 2.00]
0.77 (0.92)
1.00 (1.08)
-0.23
Number of creatinine tests ordered
...mean (sd)
0.07 (0.37)
0.06 (0.33)
0.11 (0.51)
0.06 (0.32)
0.10 (0.44)
0.10 (0.41)
0.10 (0.44)
0.08 (0.37)
0.05
...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 (0.44)
0.00 (0.37)
0.00
Number of BUN tests ordered
...mean (sd)
0.04 (0.30)
0.04 (0.27)
0.06 (0.41)
0.04 (0.28)
0.06 (0.35)
0.06 (0.33)
0.06 (0.36)
0.05 (0.30)
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 (0.36)
0.00 (0.30)
0.00
Number of tests for microalbuminuria
...mean (sd)
0.67 (1.10)
0.72 (1.12)
0.44 (0.89)
0.53 (0.98)
0.41 (0.69)
0.48 (0.75)
0.47 (0.84)
0.55 (0.92)
-0.09
...median [IQR]
0.00 [0.00, 1.00]
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 [0.00, 1.00]
0.00 (0.84)
0.00 (0.92)
0.00
Total N distinct ICD9/ICD10 diagnoses at the 3rd digit level
...mean (sd)
4.73 (7.18)
3.43 (5.80)
1.90 (4.73)
1.08 (3.22)
5.66 (8.51)
4.01 (6.97)
4.58 (7.50)
2.94 (5.74)
0.25
...median [IQR]
1.00 [0.00, 7.00]
0.00 [0.00, 5.00]
0.00 [0.00, 2.00]
0.00 [0.00, 0.00]
2.00 [0.00, 8.00]
0.00 [0.00, 6.00]
1.32 (7.50)
0.00 (5.74)
0.20
Use of thiazide; n (%)
40,916 (12.5%)
2,098 (10.1%)
42,866 (12.1%)
2,950 (10.1%)
117,483 (14.1%)
4,979 (12.1%)
201,265 (13.3%)
10,027 (11.0%)
0.07
Use of beta blockers; n (%)
126,828 (38.9%)
7,225 (34.8%)
138,568 (39.1%)
10,503 (36.0%)
390,039 (46.8%)
18,959 (46.1%)
655,435 (43.3%)
36,687 (40.3%)
0.06
Use of calcium channel blockers; n (%)
94,025 (28.8%)
5,575 (26.8%)
99,484 (28.1%)
7,927 (27.2%)
273,482 (32.8%)
13,549 (32.9%)
466,991 (30.8%)
27,051 (29.7%)
0.02
Table 1: Saxagliptin vs 2nd Generation Sulfonylureas

Variable
Reference- 2nd 
Generation SUs
Exposure- Saxagliptin
Reference- 2nd 
Generation SUs
Exposure- Saxagliptin
Reference- 2nd 
Generation SUs
Exposure- Saxagliptin
Reference- 2nd 
Generation SUs
Exposure- Saxagliptin
St. Diff.
Number of patients
20772
20772
29150
29150
41141
41141                                           91,063                                           91,063 
Age
...mean (sd)
65.97 (8.35)
66.00 (8.42)
64.00 (8.47)
64.01 (8.25)
73.91 (6.97)
73.88 (6.93)
68.93 (7.80)
68.92 (7.72)
0.00
...median [IQR]
66.00 [60.00, 71.00]
65.00 [60.00, 71.00]
62.00 [59.00, 68.00]
62.00 [59.00, 68.00]
73.00 [68.00, 78.00]
73.00 [68.00, 78.00]
67.88 (7.80)
67.65 (7.72)
0.03
Age categories 
...18 - 54; n (%)
1,121 (5.4%)
921 (4.4%)
1,719 (5.9%)
1,526 (5.2%)
0 (0.0%)
0 (0.0%)
2,840 (3.1%)
2,447 (2.7%)
0.02
...55 - 64; n (%)
7,765 (37.4%)
8,841 (42.6%)
17,220 (59.1%)
17,419 (59.8%)
868 (2.1%)
757 (1.8%)
25,853 (28.4%)
27,017 (29.7%)
-0.03
...65 - 74; n (%)
8,652 (41.7%)
7,471 (36.0%)
6,470 (22.2%)
6,582 (22.6%)
23,506 (57.1%)
23,714 (57.6%)
38,628 (42.4%)
37,767 (41.5%)
0.02
...>= 75; n (%)
3,234 (15.6%)
3,539 (17.0%)
3,741 (12.8%)
3,623 (12.4%)
16,767 (40.8%)
16,670 (40.5%)
23,742 (26.1%)
23,832 (26.2%)
0.00
Gender 
...Males; n (%)
12,157 (58.5%)
12,147 (58.5%)
17,924 (61.5%)
18,048 (61.9%)
18,432 (44.8%)
18,280 (44.4%)
48,513 (53.3%)
48,475 (53.2%)
0.00
...Females; n (%)
8,615 (41.5%)
8,625 (41.5%)
11,226 (38.5%)
11,102 (38.1%)
22,709 (55.2%)
22,861 (55.6%)
42,550 (46.7%)
42,588 (46.8%)
0.00
Race 
...White; n (%)
N/A
N/A
N/A
N/A
30,779 (74.8%)
30,782 (74.8%)
30,779 (74.8%)
30,782 (74.8%)
0.00
...Black; n (%)
N/A
N/A
N/A
N/A
4,533 (11.0%)
4,513 (11.0%)
4,533 (11.0%)
4,513 (11.0%)
0.00
...Asian; n (%)
N/A
N/A
N/A
N/A
1,883 (4.6%)
1,951 (4.7%)
1,883 (4.6%)
1,951 (4.7%)
0.00
...Hispanic; n (%)
N/A
N/A
N/A
N/A
1,960 (4.8%)
1,895 (4.6%)
1,960 (4.8%)
1,895 (4.6%)
0.01
...North American Native; n (%)
N/A
N/A
N/A
N/A
575 (1.4%)
540 (1.3%)
575 (1.4%)
540 (1.3%)
0.01
...Other/Unknown; n (%)
N/A
N/A
N/A
N/A
1,411 (3.4%)
1,460 (3.5%)
1,411 (3.4%)
1,460 (3.5%)
-0.01
Region   (lumping missing&other category with 
West)
...Northeast; n (%)
2,316 (11.1%)
2,359 (11.4%)
6,104 (20.9%)
5,957 (20.4%)
8,132 (19.8%)
8,083 (19.6%)
16,552 (18.2%)
16,399 (18.0%)
0.01
...South; n (%)
11,440 (55.1%)
11,446 (55.1%)
5,868 (20.1%)
6,007 (20.6%)
19,036 (46.3%)
18,936 (46.0%)
36,344 (39.9%)
36,389 (40.0%)
0.00
...Midwest; n (%)
3,778 (18.2%)
3,701 (17.8%)
14,089 (48.3%)
14,091 (48.3%)
7,077 (17.2%)
7,132 (17.3%)
24,944 (27.4%)
24,924 (27.4%)
0.00
...West; n (%)
3,238 (15.6%)
3,266 (15.7%)
2,716 (9.3%)
2,738 (9.4%)
6,896 (16.8%)
6,990 (17.0%)
12,850 (14.1%)
12,994 (14.3%)
-0.01
...Unknown+missing; n (%)
N/A
N/A
373 (1.3%)
357 (1.2%)
N/A
N/A
373 (1.3%)
357 (1.2%)
0.01
CV Covariates
Ischemic heart disease; n (%)
4,667 (22.5%)
4,615 (22.2%)
6,088 (20.9%)
6,045 (20.7%)
12,003 (29.2%)
11,984 (29.1%)
22,758 (25.0%)
22,644 (24.9%)
0.00
Acute MI; n (%)
233 (1.1%)
244 (1.2%)
282 (1.0%)
300 (1.0%)
483 (1.2%)
471 (1.1%)
998 (1.1%)
1,015 (1.1%)
0.00
ACS/unstable angina; n (%)
320 (1.5%)
311 (1.5%)
384 (1.3%)
374 (1.3%)
626 (1.5%)
589 (1.4%)
1,330 (1.5%)
1,274 (1.4%)
0.01
Old MI; n (%)
514 (2.5%)
524 (2.5%)
443 (1.5%)
415 (1.4%)
1,241 (3.0%)
1,318 (3.2%)
2,198 (2.4%)
2,257 (2.5%)
-0.01
Stable angina; n (%)
691 (3.3%)
662 (3.2%)
739 (2.5%)
729 (2.5%)
1,473 (3.6%)
1,494 (3.6%)
2,903 (3.2%)
2,885 (3.2%)
0.00
Coronary atherosclerosis and other forms of chronic 
ischemic heart disease; n (%)
4,278 (20.6%)
4,251 (20.5%)
5,578 (19.1%)
5,543 (19.0%)
11,376 (27.7%)
11,360 (27.6%)
21,232 (23.3%)
21,154 (23.2%)
0.00
Other atherosclerosis with ICD10 ; n (%)
222 (1.1%)
253 (1.2%)
319 (1.1%)
366 (1.3%)
835 (2.0%)
937 (2.3%)
1,376 (1.5%)
1,556 (1.7%)
-0.02
Previous cardiac procedure (CABG or PTCA or Stent) ; 
n (%)
157 (0.8%)
166 (0.8%)
201 (0.7%)
199 (0.7%)
244 (0.6%)
233 (0.6%)
602 (0.7%)
598 (0.7%)
0.00
History of CABG or PTCA; n (%)
942 (4.5%)
932 (4.5%)
665 (2.3%)
693 (2.4%)
2,928 (7.1%)
2,852 (6.9%)
4,535 (5.0%)
4,477 (4.9%)
0.00
Any stroke; n (%)
1,315 (6.3%)
1,284 (6.2%)
1,559 (5.3%)
1,582 (5.4%)
3,796 (9.2%)
3,882 (9.4%)
6,670 (7.3%)
6,748 (7.4%)
0.00
Ischemic stroke (w and w/o mention of cerebral 
infarction); n (%)
1,300 (6.3%)
1,269 (6.1%)
1,551 (5.3%)
1,568 (5.4%)
3,760 (9.1%)
3,839 (9.3%)
6,611 (7.3%)
6,676 (7.3%)
0.00
Hemorrhagic stroke; n (%)
31 (0.1%)
30 (0.1%)
22 (0.1%)
33 (0.1%)
65 (0.2%)
90 (0.2%)
118 (0.1%)
153 (0.2%)
-0.03
TIA; n (%)
312 (1.5%)
289 (1.4%)
346 (1.2%)
335 (1.1%)
872 (2.1%)
873 (2.1%)
1,530 (1.7%)
1,497 (1.6%)
0.01
Other cerebrovascular disease; n (%)
300 (1.4%)
298 (1.4%)
299 (1.0%)
289 (1.0%)
994 (2.4%)
984 (2.4%)
1,593 (1.7%)
1,571 (1.7%)
0.00
Late effects of cerebrovascular disease; n (%)
305 (1.5%)
291 (1.4%)
225 (0.8%)
220 (0.8%)
837 (2.0%)
826 (2.0%)
1,367 (1.5%)
1,337 (1.5%)
0.00
Cerebrovascular procedure; n (%)
18 (0.1%)
15 (0.1%)
28 (0.1%)
29 (0.1%)
40 (0.1%)
26 (0.1%)
086 (0.1%)
070 (0.1%)
0.00
Heart failure (CHF); n (%)
1,274 (6.1%)
1,229 (5.9%)
1,275 (4.4%)
1,274 (4.4%)
4,225 (10.3%)
4,239 (10.3%)
6,774 (7.4%)
6,742 (7.4%)
0.00
Peripheral Vascular Disease (PVD) or PVD Surgery ; n 
(%)
1,525 (7.3%)
1,479 (7.1%)
1,776 (6.1%)
1,702 (5.8%)
4,754 (11.6%)
4,859 (11.8%)
8,055 (8.8%)
8,040 (8.8%)
0.00
Atrial fibrillation; n (%)
1,271 (6.1%)
1,217 (5.9%)
1,377 (4.7%)
1,393 (4.8%)
4,481 (10.9%)
4,452 (10.8%)
7,129 (7.8%)
7,062 (7.8%)
0.00
Other cardiac dysrhythmia; n (%)
1,384 (6.7%)
1,327 (6.4%)
1,407 (4.8%)
1,413 (4.8%)
4,462 (10.8%)
4,442 (10.8%)
7,253 (8.0%)
7,182 (7.9%)
0.00
Cardiac conduction disorders; n (%)
415 (2.0%)
406 (2.0%)
431 (1.5%)
396 (1.4%)
1,446 (3.5%)
1,404 (3.4%)
2,292 (2.5%)
2,206 (2.4%)
0.01
Other CVD; n (%)
2,080 (10.0%)
1,991 (9.6%)
2,434 (8.3%)
2,357 (8.1%)
6,289 (15.3%)
6,323 (15.4%)
10,803 (11.9%)
10,671 (11.7%)
0.01
Diabetes-related complications
Diabetic retinopathy; n (%)
1,011 (4.9%)
1,005 (4.8%)
1,031 (3.5%)
1,018 (3.5%)
2,947 (7.2%)
2,806 (6.8%)
4,989 (5.5%)
4,829 (5.3%)
0.01
Diabetes with other ophthalmic manifestations; n 
(%)
82 (0.4%)
75 (0.4%)
921 (3.2%)
927 (3.2%)
1,297 (3.2%)
1,319 (3.2%)
2,300 (2.5%)
2,321 (2.5%)
0.00
Retinal detachment, vitreous hemorrhage, 
vitrectomy; n (%)
66 (0.3%)
81 (0.4%)
63 (0.2%)
86 (0.3%)
159 (0.4%)
146 (0.4%)
288 (0.3%)
313 (0.3%)
0.00
Retinal laser coagulation therapy; n (%)
112 (0.5%)
105 (0.5%)
154 (0.5%)
164 (0.6%)
261 (0.6%)
275 (0.7%)
527 (0.6%)
544 (0.6%)
0.00
Occurrence of Diabetic Neuropathy ; n (%)
2,892 (13.9%)
2,857 (13.8%)
2,320 (8.0%)
2,352 (8.1%)
7,189 (17.5%)
7,056 (17.2%)
12,401 (13.6%)
12,265 (13.5%)
0.00
Occurrence of diabetic nephropathy  with ICD10; n 
(%)
1,950 (9.4%)
1,930 (9.3%)
1,006 (3.5%)
1,037 (3.6%)
3,194 (7.8%)
3,131 (7.6%)
6,150 (6.8%)
6,098 (6.7%)
0.00
Optum
 PS-matched
MarketScan
Medicare
POOLED
Table 1: Saxagliptin vs 2nd Generation Sulfonylureas

Hypoglycemia ; n (%)
534 (2.6%)
520 (2.5%)
708 (2.4%)
710 (2.4%)
1,293 (3.1%)
1,309 (3.2%)
2,535 (2.8%)
2,539 (2.8%)
0.00
Hyperglycemia; n (%)
913 (4.4%)
914 (4.4%)
950 (3.3%)
933 (3.2%)
1,892 (4.6%)
1,907 (4.6%)
3,755 (4.1%)
3,754 (4.1%)
0.00
Disorders of fluid electrolyte and acid-base balance; n 
(%)
1,200 (5.8%)
1,202 (5.8%)
1,102 (3.8%)
1,090 (3.7%)
3,357 (8.2%)
3,443 (8.4%)
5,659 (6.2%)
5,735 (6.3%)
0.00
Diabetic ketoacidosis; n (%)
88 (0.4%)
80 (0.4%)
128 (0.4%)
97 (0.3%)
178 (0.4%)
185 (0.4%)
394 (0.4%)
362 (0.4%)
0.00
Hyperosmolar hyperglycemic nonketotic syndrome 
(HONK); n (%)
84 (0.4%)
98 (0.5%)
85 (0.3%)
88 (0.3%)
199 (0.5%)
190 (0.5%)
368 (0.4%)
376 (0.4%)
0.00
Diabetes with peripheral circulatory disorders with 
ICD-10 ; n (%)
1,044 (5.0%)
1,120 (5.4%)
865 (3.0%)
836 (2.9%)
2,944 (7.2%)
2,985 (7.3%)
4,853 (5.3%)
4,941 (5.4%)
0.00
Diabetic Foot; n (%)
335 (1.6%)
325 (1.6%)
428 (1.5%)
424 (1.5%)
1,008 (2.5%)
1,019 (2.5%)
1,771 (1.9%)
1,768 (1.9%)
0.00
Gangrene ; n (%)
44 (0.2%)
38 (0.2%)
45 (0.2%)
41 (0.1%)
52 (0.1%)
65 (0.2%)
141 (0.2%)
144 (0.2%)
0.00
Lower extremity amputation; n (%)
71 (0.3%)
72 (0.3%)
57 (0.2%)
53 (0.2%)
192 (0.5%)
177 (0.4%)
320 (0.4%)
302 (0.3%)
0.02
Osteomyelitis; n (%)
92 (0.4%)
90 (0.4%)
129 (0.4%)
123 (0.4%)
201 (0.5%)
192 (0.5%)
422 (0.5%)
405 (0.4%)
0.01
Skin infections ; n (%)
989 (4.8%)
971 (4.7%)
1,415 (4.9%)
1,382 (4.7%)
2,761 (6.7%)
2,771 (6.7%)
5,165 (5.7%)
5,124 (5.6%)
0.00
Erectile dysfunction; n (%)
787 (3.8%)
765 (3.7%)
710 (2.4%)
705 (2.4%)
1,077 (2.6%)
1,044 (2.5%)
2,574 (2.8%)
2,514 (2.8%)
0.00
Diabetes with unspecified complication; n (%)
806 (3.9%)
811 (3.9%)
803 (2.8%)
799 (2.7%)
1,639 (4.0%)
1,619 (3.9%)
3,248 (3.6%)
3,229 (3.5%)
0.01
Diabetes mellitus without mention of complications; 
n (%)
19,200 (92.4%)
19,171 (92.3%)
28,205 (96.8%)
28,166 (96.6%)
39,638 (96.3%)
39,582 (96.2%)
87,043 (95.6%)
86,919 (95.4%)
0.01
Hypertension: 1 inpatient or 2 outpatient claims 
within 365 days; n (%)
17,011 (81.9%)
16,976 (81.7%)
19,581 (67.2%)
19,540 (67.0%)
36,783 (89.4%)
36,792 (89.4%)
73,375 (80.6%)
73,308 (80.5%)
0.00
Hyperlipidemia ; n (%)
16,365 (78.8%)
16,344 (78.7%)
18,229 (62.5%)
18,157 (62.3%)
33,577 (81.6%)
33,568 (81.6%)
68,171 (74.9%)
68,069 (74.7%)
0.00
Edema; n (%)
1,188 (5.7%)
1,153 (5.6%)
1,155 (4.0%)
1,142 (3.9%)
3,729 (9.1%)
3,622 (8.8%)
6,072 (6.7%)
5,917 (6.5%)
0.01
Renal Dysfunction (non-diabetic) ; n (%)
3,426 (16.5%)
3,335 (16.1%)
2,700 (9.3%)
2,665 (9.1%)
8,387 (20.4%)
8,461 (20.6%)
14,513 (15.9%)
14,461 (15.9%)
0.00
Occurrence of acute renal disease ; n (%)
517 (2.5%)
473 (2.3%)
477 (1.6%)
435 (1.5%)
1,256 (3.1%)
1,234 (3.0%)
2,250 (2.5%)
2,142 (2.4%)
0.01
Occurrence of chronic renal insufficiency; n (%)
2,611 (12.6%)
2,601 (12.5%)
1,723 (5.9%)
1,713 (5.9%)
6,558 (15.9%)
6,642 (16.1%)
10,892 (12.0%)
10,956 (12.0%)
0.00
Chronic kidney disease ; n (%)
2,470 (11.9%)
2,480 (11.9%)
1,614 (5.5%)
1,643 (5.6%)
6,118 (14.9%)
6,213 (15.1%)
10,202 (11.2%)
10,336 (11.4%)
-0.01
CKD Stage 3-4; n (%)
1,612 (7.8%)
1,589 (7.6%)
995 (3.4%)
993 (3.4%)
4,059 (9.9%)
4,042 (9.8%)
6,666 (7.3%)
6,624 (7.3%)
0.00
Occurrence of hypertensive nephropathy; n (%)
1,054 (5.1%)
1,007 (4.8%)
637 (2.2%)
634 (2.2%)
2,624 (6.4%)
2,658 (6.5%)
4,315 (4.7%)
4,299 (4.7%)
0.00
Occurrence of miscellaneous renal insufficiency ; n 
(%)
1,124 (5.4%)
1,039 (5.0%)
1,050 (3.6%)
974 (3.3%)
3,066 (7.5%)
3,095 (7.5%)
5,240 (5.8%)
5,108 (5.6%)
0.01
Glaucoma or cataracts ; n (%)
3,957 (19.0%)
3,868 (18.6%)
4,501 (15.4%)
4,474 (15.3%)
11,477 (27.9%)
11,808 (28.7%)
19,935 (21.9%)
20,150 (22.1%)
0.00
Cellulitis or abscess of toe; n (%)
192 (0.9%)
184 (0.9%)
183 (0.6%)
184 (0.6%)
387 (0.9%)
352 (0.9%)
762 (0.8%)
720 (0.8%)
0.00
Foot ulcer; n (%)
332 (1.6%)
320 (1.5%)
444 (1.5%)
438 (1.5%)
1,033 (2.5%)
1,031 (2.5%)
1,809 (2.0%)
1,789 (2.0%)
0.00
Bladder stones; n (%)
37 (0.2%)
33 (0.2%)
32 (0.1%)
33 (0.1%)
97 (0.2%)
75 (0.2%)
166 (0.2%)
141 (0.2%)
0.00
Kidney stones; n (%)
557 (2.7%)
502 (2.4%)
689 (2.4%)
627 (2.2%)
1,207 (2.9%)
1,198 (2.9%)
2,453 (2.7%)
2,327 (2.6%)
0.01
Urinary tract infections (UTIs); n (%)
1,686 (8.1%)
1,703 (8.2%)
1,779 (6.1%)
1,725 (5.9%)
6,277 (15.3%)
6,276 (15.3%)
9,742 (10.7%)
9,704 (10.7%)
0.00
Dipstick urinalysis; n (%)
7,535 (36.3%)
7,904 (38.1%)
9,562 (32.8%)
9,919 (34.0%)
17,882 (43.5%)
18,912 (46.0%)
34,979 (38.4%)
36,735 (40.3%)
-0.04
Non-dipstick urinalysis; n (%)
8,224 (39.6%)
8,380 (40.3%)
9,173 (31.5%)
9,298 (31.9%)
16,448 (40.0%)
16,601 (40.4%)
33,845 (37.2%)
34,279 (37.6%)
-0.01
Urine function test; n (%)
541 (2.6%)
522 (2.5%)
797 (2.7%)
798 (2.7%)
1,782 (4.3%)
1,710 (4.2%)
3,120 (3.4%)
3,030 (3.3%)
0.01
Cytology; n (%)
227 (1.1%)
221 (1.1%)
393 (1.3%)
393 (1.3%)
740 (1.8%)
757 (1.8%)
1,360 (1.5%)
1,371 (1.5%)
0.00
Cystos; n (%)
350 (1.7%)
351 (1.7%)
516 (1.8%)
535 (1.8%)
969 (2.4%)
979 (2.4%)
1,835 (2.0%)
1,865 (2.0%)
0.00
Other Covariates
Liver disease; n (%)
1,041 (5.0%)
1,007 (4.8%)
964 (3.3%)
951 (3.3%)
2,109 (5.1%)
2,120 (5.2%)
4,114 (4.5%)
4,078 (4.5%)
0.00
Osteoarthritis; n (%)
2,964 (14.3%)
2,939 (14.1%)
3,120 (10.7%)
3,066 (10.5%)
9,491 (23.1%)
9,594 (23.3%)
15,575 (17.1%)
15,599 (17.1%)
0.00
Other arthritis, arthropathies and musculoskeletal 
pain; n (%)
6,815 (32.8%)
6,756 (32.5%)
8,386 (28.8%)
8,254 (28.3%)
18,345 (44.6%)
18,289 (44.5%)
33,546 (36.8%)
33,299 (36.6%)
0.00
Dorsopathies; n (%)
4,125 (19.9%)
4,111 (19.8%)
5,015 (17.2%)
4,993 (17.1%)
11,187 (27.2%)
11,235 (27.3%)
20,327 (22.3%)
20,339 (22.3%)
0.00
Fractures; n (%)
473 (2.3%)
464 (2.2%)
630 (2.2%)
623 (2.1%)
1,539 (3.7%)
1,478 (3.6%)
2,642 (2.9%)
2,565 (2.8%)
0.01
Falls ; n (%)
400 (1.9%)
421 (2.0%)
175 (0.6%)
172 (0.6%)
1,378 (3.3%)
1,361 (3.3%)
1,953 (2.1%)
1,954 (2.1%)
0.00
Osteoporosis; n (%)
1,213 (5.8%)
1,166 (5.6%)
1,066 (3.7%)
1,105 (3.8%)
4,387 (10.7%)
4,452 (10.8%)
6,666 (7.3%)
6,723 (7.4%)
0.00
Hyperthyroidism; n (%)
141 (0.7%)
142 (0.7%)
154 (0.5%)
145 (0.5%)
484 (1.2%)
456 (1.1%)
779 (0.9%)
743 (0.8%)
0.01
Hypothyroidism ; n (%)
3,175 (15.3%)
3,119 (15.0%)
3,017 (10.3%)
2,931 (10.1%)
8,320 (20.2%)
8,090 (19.7%)
14,512 (15.9%)
14,140 (15.5%)
0.01
Other disorders of thyroid gland ; n (%)
691 (3.3%)
730 (3.5%)
868 (3.0%)
889 (3.0%)
2,014 (4.9%)
2,248 (5.5%)
3,573 (3.9%)
3,867 (4.2%)
-0.02
Depression; n (%)
1,417 (6.8%)
1,395 (6.7%)
1,524 (5.2%)
1,455 (5.0%)
4,115 (10.0%)
4,149 (10.1%)
7,056 (7.7%)
6,999 (7.7%)
0.00
Anxiety; n (%)
1,150 (5.5%)
1,110 (5.3%)
1,033 (3.5%)
976 (3.3%)
3,117 (7.6%)
3,190 (7.8%)
5,300 (5.8%)
5,276 (5.8%)
0.00
Sleep_Disorder; n (%)
1,846 (8.9%)
1,817 (8.7%)
2,953 (10.1%)
2,943 (10.1%)
3,774 (9.2%)
3,794 (9.2%)
8,573 (9.4%)
8,554 (9.4%)
0.00
Dementia; n (%)
520 (2.5%)
513 (2.5%)
436 (1.5%)
417 (1.4%)
2,620 (6.4%)
2,659 (6.5%)
3,576 (3.9%)
3,589 (3.9%)
0.00
Delirium; n (%)
139 (0.7%)
127 (0.6%)
150 (0.5%)
136 (0.5%)
569 (1.4%)
577 (1.4%)
858 (0.9%)
840 (0.9%)
0.00
Psychosis; n (%)
116 (0.6%)
125 (0.6%)
149 (0.5%)
139 (0.5%)
704 (1.7%)
696 (1.7%)
969 (1.1%)
960 (1.1%)
0.00
Obesity; n (%)
2,583 (12.4%)
2,589 (12.5%)
1,765 (6.1%)
1,801 (6.2%)
4,272 (10.4%)
4,255 (10.3%)
8,620 (9.5%)
8,645 (9.5%)
0.00
Overweight; n (%)
752 (3.6%)
748 (3.6%)
279 (1.0%)
279 (1.0%)
1,140 (2.8%)
1,164 (2.8%)
2,171 (2.4%)
2,191 (2.4%)
0.00
Smoking; n (%)
1,718 (8.3%)
1,667 (8.0%)
1,199 (4.1%)
1,207 (4.1%)
4,251 (10.3%)
4,199 (10.2%)
7,168 (7.9%)
7,073 (7.8%)
0.00
Alcohol abuse or dependence; n (%)
155 (0.7%)
152 (0.7%)
157 (0.5%)
134 (0.5%)
244 (0.6%)
249 (0.6%)
556 (0.6%)
535 (0.6%)
0.00
Drug abuse or dependence; n (%)
169 (0.8%)
169 (0.8%)
102 (0.3%)
101 (0.3%)
287 (0.7%)
280 (0.7%)
558 (0.6%)
550 (0.6%)
0.00
COPD; n (%)
1,529 (7.4%)
1,480 (7.1%)
1,507 (5.2%)
1,500 (5.1%)
4,727 (11.5%)
4,617 (11.2%)
7,763 (8.5%)
7,597 (8.3%)
0.01
Asthma; n (%)
979 (4.7%)
1,013 (4.9%)
1,122 (3.8%)
1,110 (3.8%)
2,606 (6.3%)
2,618 (6.4%)
4,707 (5.2%)
4,741 (5.2%)
0.00
Obstructive sleep apnea; n (%)
1,620 (7.8%)
1,611 (7.8%)
2,321 (8.0%)
2,286 (7.8%)
2,171 (5.3%)
2,191 (5.3%)
6,112 (6.7%)
6,088 (6.7%)
0.00
Table 1: Saxagliptin vs 2nd Generation Sulfonylureas

Pneumonia; n (%)
379 (1.8%)
378 (1.8%)
460 (1.6%)
466 (1.6%)
1,272 (3.1%)
1,258 (3.1%)
2,111 (2.3%)
2,102 (2.3%)
0.00
Imaging; n (%)
34 (0.2%)
19 (0.1%)
16 (0.1%)
17 (0.1%)
54 (0.1%)
51 (0.1%)
104 (0.1%)
87 (0.1%)
0.00
Diabetes Medications
DM Medications - AGIs; n (%)
63 (0.3%)
65 (0.3%)
93 (0.3%)
80 (0.3%)
179 (0.4%)
192 (0.5%)
335 (0.4%)
337 (0.4%)
0.00
DM Medications - Glitazones; n (%)
2,628 (12.7%)
2,617 (12.6%)
5,543 (19.0%)
5,541 (19.0%)
4,414 (10.7%)
4,429 (10.8%)
12,585 (13.8%)
12,587 (13.8%)
0.00
DM Medications - GLP-1 RA; n (%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
#VALUE!
#VALUE!
#VALUE!
DM Medications - Insulin; n (%)
3,259 (15.7%)
3,169 (15.3%)
3,930 (13.5%)
3,878 (13.3%)
7,703 (18.7%)
7,651 (18.6%)
14,892 (16.4%)
14,698 (16.1%)
0.01
DM Medications - Meglitinides; n (%)
334 (1.6%)
334 (1.6%)
752 (2.6%)
774 (2.7%)
1,119 (2.7%)
1,129 (2.7%)
2,205 (2.4%)
2,237 (2.5%)
-0.01
DM Medications - Metformin; n (%)
14,469 (69.7%)
14,670 (70.6%)
21,163 (72.6%)
21,117 (72.4%)
27,388 (66.6%)
27,400 (66.6%)
63,020 (69.2%)
63,187 (69.4%)
0.00
Concomitant initiation or current use of SGLT2i; n 
(%)
569 (2.7%)
540 (2.6%)
344 (1.2%)
349 (1.2%)
508 (1.2%)
516 (1.3%)
1,421 (1.6%)
1,405 (1.5%)
0.01
Concomitant initiation or current use of AGIs; n (%)
55 (0.3%)
45 (0.2%)
64 (0.2%)
49 (0.2%)
121 (0.3%)
125 (0.3%)
240 (0.3%)
219 (0.2%)
0.02
Concomitant initiation or current use of Glitazones; 
n (%)
1,515 (7.3%)
1,495 (7.2%)
3,216 (11.0%)
3,195 (11.0%)
2,710 (6.6%)
2,669 (6.5%)
7,441 (8.2%)
7,359 (8.1%)
0.00
Concomitant initiation or current use of GLP-1 RA; 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!
Concomitant initiation or current use of Insulin; n 
(%)
2,393 (11.5%)
2,338 (11.3%)
2,955 (10.1%)
2,911 (10.0%)
5,862 (14.2%)
5,819 (14.1%)
11,210 (12.3%)
11,068 (12.2%)
0.00
Concomitant initiation or current use of 
Meglitinides; n (%)
234 (1.1%)
236 (1.1%)
501 (1.7%)
559 (1.9%)
790 (1.9%)
800 (1.9%)
1,525 (1.7%)
1,595 (1.8%)
-0.01
Concomitant initiation or current use of Metformin; 
n (%)
12,550 (60.4%)
12,734 (61.3%)
18,351 (63.0%)
18,424 (63.2%)
23,232 (56.5%)
23,281 (56.6%)
54,133 (59.4%)
54,439 (59.8%)
-0.01
Past use of SGLT2i; n (%)
232 (1.1%)
234 (1.1%)
108 (0.4%)
119 (0.4%)
203 (0.5%)
197 (0.5%)
543 (0.6%)
550 (0.6%)
0.00
Past use of AGIs; n (%)
8 (0.0%)
20 (0.1%)
29 (0.1%)
31 (0.1%)
58 (0.1%)
67 (0.2%)
095 (0.1%)
118 (0.1%)
0.00
Past use of Glitazones; n (%)
1,113 (5.4%)
1,122 (5.4%)
2,328 (8.0%)
2,346 (8.0%)
1,704 (4.1%)
1,760 (4.3%)
5,145 (5.6%)
5,228 (5.7%)
0.00
Past use of GLP-1 RA; 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!
Past use of Insulin; n (%)
866 (4.2%)
831 (4.0%)
975 (3.3%)
967 (3.3%)
1,841 (4.5%)
1,832 (4.5%)
3,682 (4.0%)
3,630 (4.0%)
0.00
Past use of Meglitinides; n (%)
100 (0.5%)
98 (0.5%)
251 (0.9%)
215 (0.7%)
329 (0.8%)
329 (0.8%)
680 (0.7%)
642 (0.7%)
0.00
Past use of metformin (final); n (%)
1,919 (9.2%)
1,936 (9.3%)
2,812 (9.6%)
2,693 (9.2%)
4,156 (10.1%)
4,119 (10.0%)
8,887 (9.8%)
8,748 (9.6%)
0.01
Other Medications
Use of ACE inhibitors; n (%)
8,548 (41.2%)
8,588 (41.3%)
12,091 (41.5%)
12,183 (41.8%)
16,283 (39.6%)
16,298 (39.6%)
36,922 (40.5%)
37,069 (40.7%)
0.00
Use of ARBs; n (%)
6,027 (29.0%)
6,014 (29.0%)
9,104 (31.2%)
9,054 (31.1%)
13,919 (33.8%)
13,948 (33.9%)
29,050 (31.9%)
29,016 (31.9%)
0.00
Use of Loop Diuretics ; n (%)
2,050 (9.9%)
2,094 (10.1%)
3,016 (10.3%)
2,970 (10.2%)
7,243 (17.6%)
7,190 (17.5%)
12,309 (13.5%)
12,254 (13.5%)
0.00
Use of other diuretics; n (%)
487 (2.3%)
491 (2.4%)
679 (2.3%)
707 (2.4%)
1,337 (3.2%)
1,357 (3.3%)
2,503 (2.7%)
2,555 (2.8%)
-0.01
Use of nitrates-United; n (%)
972 (4.7%)
970 (4.7%)
1,432 (4.9%)
1,429 (4.9%)
3,294 (8.0%)
3,287 (8.0%)
5,698 (6.3%)
5,686 (6.2%)
0.00
Use of other hypertension drugs; n (%)
1,261 (6.1%)
1,250 (6.0%)
1,563 (5.4%)
1,535 (5.3%)
3,298 (8.0%)
3,334 (8.1%)
6,122 (6.7%)
6,119 (6.7%)
0.00
Use of digoxin; n (%)
412 (2.0%)
368 (1.8%)
600 (2.1%)
605 (2.1%)
1,533 (3.7%)
1,512 (3.7%)
2,545 (2.8%)
2,485 (2.7%)
0.01
Use of Anti-arrhythmics; n (%)
213 (1.0%)
211 (1.0%)
332 (1.1%)
348 (1.2%)
836 (2.0%)
819 (2.0%)
1,381 (1.5%)
1,378 (1.5%)
0.00
Use of COPD/asthma meds; n (%)
2,785 (13.4%)
2,794 (13.5%)
4,169 (14.3%)
4,167 (14.3%)
7,710 (18.7%)
7,674 (18.7%)
14,664 (16.1%)
14,635 (16.1%)
0.00
Use of statins; n (%)
13,588 (65.4%)
13,603 (65.5%)
19,039 (65.3%)
18,973 (65.1%)
28,374 (69.0%)
28,291 (68.8%)
61,001 (67.0%)
60,867 (66.8%)
0.00
Use of other lipid-lowering drugs; n (%)
3,030 (14.6%)
2,944 (14.2%)
5,019 (17.2%)
4,897 (16.8%)
5,994 (14.6%)
5,973 (14.5%)
14,043 (15.4%)
13,814 (15.2%)
0.01
Use of antiplatelet agents; n (%)
2,640 (12.7%)
2,605 (12.5%)
4,128 (14.2%)
4,089 (14.0%)
6,851 (16.7%)
6,953 (16.9%)
13,619 (15.0%)
13,647 (15.0%)
0.00
Use of oral anticoagulants (Dabigatran, Rivaroxaban, 
Apixaban, Warfarin); n (%)
1,112 (5.4%)
1,077 (5.2%)
1,464 (5.0%)
1,445 (5.0%)
3,637 (8.8%)
3,537 (8.6%)
6,213 (6.8%)
6,059 (6.7%)
0.00
Use of heparin and other low-molecular weight 
heparins; n (%)
94 (0.5%)
90 (0.4%)
0 (0.0%)
1 (0.0%)
177 (0.4%)
169 (0.4%)
271 (0.3%)
260 (0.3%)
0.00
Use of NSAIDs; n (%)
3,123 (15.0%)
3,100 (14.9%)
4,272 (14.7%)
4,343 (14.9%)
7,170 (17.4%)
7,301 (17.7%)
14,565 (16.0%)
14,744 (16.2%)
-0.01
Use of oral corticosteroids; n (%)
2,722 (13.1%)
2,663 (12.8%)
3,635 (12.5%)
3,677 (12.6%)
6,754 (16.4%)
6,571 (16.0%)
13,111 (14.4%)
12,911 (14.2%)
0.01
Use of bisphosphonate (United); n (%)
628 (3.0%)
603 (2.9%)
612 (2.1%)
637 (2.2%)
1,921 (4.7%)
1,970 (4.8%)
3,161 (3.5%)
3,210 (3.5%)
0.00
Use of opioids; n (%)
4,763 (22.9%)
4,735 (22.8%)
7,046 (24.2%)
6,977 (23.9%)
10,491 (25.5%)
10,563 (25.7%)
22,300 (24.5%)
22,275 (24.5%)
0.00
Use of antidepressants; n (%)
4,125 (19.9%)
4,035 (19.4%)
5,686 (19.5%)
5,621 (19.3%)
10,351 (25.2%)
10,384 (25.2%)
20,162 (22.1%)
20,040 (22.0%)
0.00
Use of antipsychotics; n (%)
358 (1.7%)
369 (1.8%)
454 (1.6%)
432 (1.5%)
1,440 (3.5%)
1,456 (3.5%)
2,252 (2.5%)
2,257 (2.5%)
0.00
Use of anticonvulsants; n (%)
2,400 (11.6%)
2,374 (11.4%)
2,784 (9.6%)
2,730 (9.4%)
6,445 (15.7%)
6,460 (15.7%)
11,629 (12.8%)
11,564 (12.7%)
0.00
Use of lithium; n (%)
22 (0.1%)
23 (0.1%)
45 (0.2%)
26 (0.1%)
66 (0.2%)
43 (0.1%)
133 (0.1%)
092 (0.1%)
0.00
Use of Benzos; n (%)
1,724 (8.3%)
1,648 (7.9%)
2,989 (10.3%)
2,963 (10.2%)
3,802 (9.2%)
3,787 (9.2%)
8,515 (9.4%)
8,398 (9.2%)
0.01
Use of anxiolytics/hypnotics; n (%)
1,306 (6.3%)
1,300 (6.3%)
2,107 (7.2%)
1,988 (6.8%)
3,334 (8.1%)
3,334 (8.1%)
6,747 (7.4%)
6,622 (7.3%)
0.00
Use of dementia meds; n (%)
360 (1.7%)
361 (1.7%)
378 (1.3%)
365 (1.3%)
2,292 (5.6%)
2,350 (5.7%)
3,030 (3.3%)
3,076 (3.4%)
-0.01
Use of antiparkinsonian meds; n (%)
401 (1.9%)
410 (2.0%)
571 (2.0%)
556 (1.9%)
1,325 (3.2%)
1,332 (3.2%)
2,297 (2.5%)
2,298 (2.5%)
0.00
Any use of pramlintide; n (%)
8 (0.0%)
11 (0.1%)
20 (0.1%)
38 (0.1%)
5 (0.0%)
12 (0.0%)
033 (0.0%)
061 (0.1%)
-0.04
Any use of 1st generation sulfonylureas; n (%)
3 (0.0%)
5 (0.0%)
21 (0.1%)
8 (0.0%)
31 (0.1%)
19 (0.0%)
055 (0.1%)
032 (0.0%)
0.00
Entresto (sacubitril/valsartan); n (%)
9 (0.0%)
16 (0.1%)
1 (0.0%)
1 (0.0%)
6 (0.0%)
11 (0.0%)
016 (0.0%)
028 (0.0%)
0.00
Initiation as monotherapy ; n (%)
4,379 (21.1%)
4,352 (21.0%)
5,359 (18.4%)
5,432 (18.6%)
6,352 (15.4%)
6,427 (15.6%)
16,090 (17.7%)
16,211 (17.8%)
0.00
Labs
                                          49,922                                           49,922 
Lab values- HbA1c (%) ; n (%)
6,855 (33.0%)
7,389 (35.6%)
1,708 (5.9%)
1,595 (5.5%)
N/A
N/A
8,563 (17.2%)
8,984 (18.0%)
-0.02
Lab values- HbA1c (%) (within 3 months) ; n (%)
5,387 (25.9%)
5,927 (28.5%)
1,324 (4.5%)
1,266 (4.3%)
N/A
N/A
6,711 (13.4%)
7,193 (14.4%)
-0.03
Lab values- HbA1c (%) (within 6 months) ; n (%)
6,855 (33.0%)
7,389 (35.6%)
1,708 (5.9%)
1,595 (5.5%)
N/A
N/A
8,563 (17.2%)
8,984 (18.0%)
-0.02
Lab values- BNP; n (%)
95 (0.5%)
97 (0.5%)
13 (0.0%)
19 (0.1%)
N/A
N/A
108 (0.2%)
116 (0.2%)
0.00
Table 1: Saxagliptin vs 2nd Generation Sulfonylureas

Lab values- BNP (within 3 months); n (%)
54 (0.3%)
60 (0.3%)
5 (0.0%)
10 (0.0%)
N/A
N/A
059 (0.1%)
070 (0.1%)
0.00
Lab values- BNP (within 6 months); n (%)
95 (0.5%)
97 (0.5%)
13 (0.0%)
19 (0.1%)
N/A
N/A
108 (0.2%)
116 (0.2%)
0.00
Lab values- BUN (mg/dl); n (%)
7,159 (34.5%)
7,737 (37.2%)
1,493 (5.1%)
1,670 (5.7%)
N/A
N/A
8,652 (17.3%)
9,407 (18.8%)
-0.04
Lab values- BUN (mg/dl) (within 3 months); n (%)
5,533 (26.6%)
6,143 (29.6%)
1,160 (4.0%)
1,300 (4.5%)
N/A
N/A
6,693 (13.4%)
7,443 (14.9%)
-0.04
Lab values- BUN (mg/dl) (within 6 months); n (%)
7,159 (34.5%)
7,737 (37.2%)
1,493 (5.1%)
1,670 (5.7%)
N/A
N/A
8,652 (17.3%)
9,407 (18.8%)
-0.04
Lab values- Creatinine (mg/dl) ; n (%)
7,273 (35.0%)
7,904 (38.1%)
1,541 (5.3%)
1,728 (5.9%)
N/A
N/A
8,814 (17.7%)
9,632 (19.3%)
-0.04
Lab values- Creatinine (mg/dl) (within 3 months) ; n 
(%)
5,629 (27.1%)
6,283 (30.2%)
1,192 (4.1%)
1,342 (4.6%)
N/A
N/A
6,821 (13.7%)
7,625 (15.3%)
-0.05
Lab values- Creatinine (mg/dl) (within 6 months) ; n 
(%)
7,273 (35.0%)
7,904 (38.1%)
1,541 (5.3%)
1,728 (5.9%)
N/A
N/A
8,814 (17.7%)
9,632 (19.3%)
-0.04
Lab values- HDL level (mg/dl); n (%)
6,230 (30.0%)
6,623 (31.9%)
1,540 (5.3%)
1,484 (5.1%)
N/A
N/A
7,770 (15.6%)
8,107 (16.2%)
-0.02
Lab values- HDL level (mg/dl) (within 3 months); n (%)
4,634 (22.3%)
5,024 (24.2%)
1,143 (3.9%)
1,117 (3.8%)
N/A
N/A
5,777 (11.6%)
6,141 (12.3%)
-0.02
Lab values- HDL level (mg/dl) (within 6 months); n (%)
6,230 (30.0%)
6,623 (31.9%)
1,540 (5.3%)
1,484 (5.1%)
N/A
N/A
7,770 (15.6%)
8,107 (16.2%)
-0.02
Lab values- LDL level (mg/dl) ; n (%)
6,312 (30.4%)
6,695 (32.2%)
1,631 (5.6%)
1,508 (5.2%)
N/A
N/A
7,943 (15.9%)
8,203 (16.4%)
-0.01
Lab values- LDL level (mg/dl) (within 3 months) ; n (%)
4,683 (22.5%)
5,091 (24.5%)
1,211 (4.2%)
1,133 (3.9%)
N/A
N/A
5,894 (11.8%)
6,224 (12.5%)
-0.02
Lab values- LDL level (mg/dl) (within 6 months) ; n (%)
6,312 (30.4%)
6,695 (32.2%)
1,631 (5.6%)
1,508 (5.2%)
N/A
N/A
7,943 (15.9%)
8,203 (16.4%)
-0.01
Lab values- NT-proBNP; n (%)
6 (0.0%)
18 (0.1%)
0 (0.0%)
1 (0.0%)
N/A
N/A
06 (0.0%)
0 (0.0%)
-
Lab values- NT-proBNP (within 3 months); n (%)
5 (0.0%)
13 (0.1%)
0 (0.0%)
1 (0.0%)
N/A
N/A
05 (0.0%)
0 (0.0%)
-
Lab values- NT-proBNP (within 6 months); n (%)
6 (0.0%)
18 (0.1%)
0 (0.0%)
1 (0.0%)
N/A
N/A
06 (0.0%)
19 (0.0%)
-
Lab values- Total cholesterol (mg/dl) ; n (%)
6,283 (30.2%)
6,730 (32.4%)
1,564 (5.4%)
1,521 (5.2%)
N/A
N/A
7,847 (15.7%)
8,251 (16.5%)
-0.02
Lab values- Total cholesterol (mg/dl) (within 3 
months) ; n (%)
4,661 (22.4%)
5,114 (24.6%)
1,155 (4.0%)
1,147 (3.9%)
N/A
N/A
5,816 (11.7%)
6,261 (12.5%)
-0.02
Lab values- Total cholesterol (mg/dl) (within 6 
months) ; n (%)
6,283 (30.2%)
6,730 (32.4%)
1,564 (5.4%)
1,521 (5.2%)
N/A
N/A
7,847 (15.7%)
8,251 (16.5%)
-0.02
Lab values- Triglyceride level (mg/dl); n (%)
6,237 (30.0%)
6,704 (32.3%)
1,531 (5.3%)
1,485 (5.1%)
N/A
N/A
7,768 (15.6%)
8,189 (16.4%)
-0.02
Lab values- Triglyceride level (mg/dl) (within 3 
months); n (%)
4,640 (22.3%)
5,099 (24.5%)
1,134 (3.9%)
1,118 (3.8%)
N/A
N/A
5,774 (11.6%)
6,217 (12.5%)
-0.03
Lab values- Triglyceride level (mg/dl) (within 6 
months); n (%)
6,237 (30.0%)
6,704 (32.3%)
1,531 (5.3%)
1,485 (5.1%)
N/A
N/A
7,768 (15.6%)
8,189 (16.4%)
-0.02
Lab result number- HbA1c (%) mean (only 2 to 20 
included) 
6,825
                                            
7,368
                                            
1,534
                                            
1,504
                                            
N/A
N/A                                              8,359                                              8,872 
...mean (sd)
8.18 (1.81)
7.95 (1.71)
8.20 (1.81)
8.03 (1.81)
N/A
N/A
8.18 (1.81)
7.96 (1.73)
0.12
...median [IQR]
7.70 [6.95, 9.00]
7.50 [6.80, 8.65]
7.70 [7.00, 9.00]
7.50 [6.80, 8.70]
N/A
N/A
7.70 (1.81)
7.50 (1.73)
0.11
...Missing; n (%)
13,947 (67.1%)
13,404 (64.5%)
27,616 (94.7%)
27,646 (94.8%)
N/A
N/A
41,563 (83.3%)
41,050 (82.2%)
0.03
Lab result number- BNP mean 
95
                                                   
97
                                                   
13
                                                   
19
                                                   
N/A
N/A                                                  108                                                  116 
...mean (sd)
164.54 (440.30)
152.44 (201.22)
116.99 (165.82)
238.55 (559.75)
N/A
N/A
158.82 (420.35)
166.54 (290.36)
-0.02
...median [IQR]
72.10 [21.70, 154.80]
85.00 [32.40, 195.85]
46.40 [21.45, 142.90]
30.00 [17.00, 112.00]
N/A
N/A
#VALUE!
#VALUE!
#VALUE!
...Missing; n (%)
20,677 (99.5%)
20,675 (99.5%)
29,137 (100.0%)
29,131 (99.9%)
N/A
N/A
49,814 (99.8%)
49,806 (99.8%)
0.00
Lab result number- BUN (mg/dl) mean 
                                             7,159                                              7,737                                              1,493                                              1,670 
N/A
N/A                                              8,652                                              9,407 
...mean (sd)
18.18 (7.32)
18.03 (7.12)
472.97 (9,177.52)
373.82 (7,794.27)
N/A
N/A
96.66 (3811.78)
81.19 (3283.58)
0.00
...median [IQR]
17.00 [13.50, 21.00]
16.50 [13.50, 21.00]
17.00 [14.00, 20.50]
17.00 [13.00, 20.00]
N/A
N/A
#VALUE!
#VALUE!
#VALUE!
...Missing; n (%)
13,613 (65.5%)
13,035 (62.8%)
27,657 (94.9%)
27,480 (94.3%)
N/A
N/A
41,270 (82.7%)
40,515 (81.2%)
0.04
Lab result number- Creatinine (mg/dl) mean (only 0.1 
to 15 included) 
                                             7,235                                              7,867                                              1,505                                              1,683 
N/A
N/A                                              8,740                                              9,550 
...mean (sd)
1.01 (0.36)
1.01 (0.35)
0.97 (0.29)
0.99 (0.33)
N/A
N/A
1.00 (0.35)
1.01 (0.35)
-0.03
...median [IQR]
0.94 [0.79, 1.14]
0.95 [0.80, 1.13]
0.93 [0.79, 1.09]
0.93 [0.80, 1.10]
N/A
N/A
0.94 (0.35)
0.95 (0.35)
-0.03
...Missing; n (%)
13,537 (65.2%)
12,905 (62.1%)
27,645 (94.8%)
27,467 (94.2%)
N/A
N/A
41,182 (82.5%)
40,372 (80.9%)
0.04
Lab result number- HDL level (mg/dl) mean (only 
=<5000 included) 
                                             6,230                                              6,623                                              1,539                                              1,481 
N/A
N/A                                              7,769                                              8,104 
...mean (sd)
45.66 (13.30)
46.38 (13.32)
44.68 (13.91)
45.39 (13.98)
N/A
N/A
45.47 (13.42)
46.20 (13.44)
-0.05
...median [IQR]
44.00 [37.00, 53.00]
44.00 [37.00, 53.00]
43.00 [36.00, 52.00]
44.00 [37.00, 52.50]
N/A
N/A
43.80 (13.42)
44.00 (13.44)
-0.01
...Missing; n (%)
14,542 (70.0%)
14,149 (68.1%)
27,611 (94.7%)
27,669 (94.9%)
N/A
N/A
42,153 (84.4%)
41,818 (83.8%)
0.02
Lab result number- LDL level (mg/dl) mean (only 
=<5000 included) 
                                             6,194                                              6,595                                              1,490                                              1,436 
N/A
N/A                                              7,684                                              8,031 
...mean (sd)
87.61 (40.85)
87.44 (38.52)
87.29 (41.68)
89.25 (40.99)
N/A
N/A
87.55 (41.01)
87.76 (38.98)
-0.01
...median [IQR]
85.00 [63.00, 112.00]
84.00 [64.00, 109.00]
86.00 [63.44, 113.00]
87.00 [65.00, 112.38]
N/A
N/A
85.19 (41.01)
84.54 (38.98)
0.02
...Missing; n (%)
14,578 (70.2%)
14,177 (68.3%)
27,660 (94.9%)
27,714 (95.1%)
N/A
N/A
42,238 (84.6%)
41,891 (83.9%)
0.02
Lab result number- Total cholesterol (mg/dl) mean 
(only =<5000 included) 
                                             6,281                                              6,727                                              1,562                                              1,515 
N/A
N/A                                              7,843                                              8,242 
...mean (sd)
176.40 (48.75)
172.97 (46.09)
176.21 (49.12)
174.96 (49.83)
N/A
N/A
176.36 (48.83)
173.34 (46.80)
0.06
...median [IQR]
170.00 [144.00, 201.00]
166.00 [143.00, 197.00]
172.00 [145.50, 203.00]
169.50 [145.50, 201.00]
N/A
N/A
170.40 (48.83)
166.64 (46.80)
0.08
...Missing; n (%)
14,491 (69.8%)
14,045 (67.6%)
27,588 (94.6%)
27,635 (94.8%)
N/A
N/A
42,079 (84.3%)
41,680 (83.5%)
0.02
Lab result number- Triglyceride level (mg/dl) mean 
(only =<5000 included) 
                                             6,236                                              6,703                                              1,530                                              1,482 
N/A
N/A                                              7,766                                              8,185 
Table 1: Saxagliptin vs 2nd Generation Sulfonylureas

...mean (sd)
198.52 (201.95)
179.80 (153.29)
201.91 (196.77)
188.19 (193.76)
N/A
N/A
199.19 (200.95)
181.32 (161.38)
0.10
...median [IQR]
155.00 [109.00, 225.88]
147.50 [105.00, 210.00]
157.00 [109.00, 231.00]
150.00 [103.00, 221.00]
N/A
N/A
155.39 (200.95)
147.95 (161.38)
0.04
...Missing; n (%)
14,536 (70.0%)
14,069 (67.7%)
27,620 (94.8%)
27,668 (94.9%)
N/A
N/A
42,156 (84.4%)
41,737 (83.6%)
0.02
Lab result number- Hemoglobin mean (only >0 
included)
                                             5,023                                              5,290                                                  944                                              1,027 
N/A
N/A                                              5,967                                              6,317 
...mean (sd)
13.70 (1.67)
13.72 (1.69)
11,075.13 (325,562.43)
522.41 (8,421.85)
N/A
N/A
1763.66 (129455.74)
96.42 (3394.92)
0.02
...median [IQR]
13.80 [12.60, 14.80]
13.80 [12.60, 14.90]
13.90 [12.80, 15.00]
14.00 [12.90, 15.00]
N/A
N/A
#VALUE!
#VALUE!
#VALUE!
...Missing; n (%)
15,749 (75.8%)
15,482 (74.5%)
28,206 (96.8%)
28,123 (96.5%)
N/A
N/A
43,955 (88.0%)
43,605 (87.3%)
0.02
Lab result number- Serum sodium mean (only > 90 
and < 190 included)
                                             7,115                                              7,732                                              1,415                                              1,597 
N/A
N/A                                              8,530                                              9,329 
...mean (sd)
139.13 (2.80)
139.38 (2.70)
138.84 (2.60)
138.94 (2.61)
N/A
N/A
139.08 (2.77)
139.30 (2.68)
-0.08
...median [IQR]
139.00 [137.67, 141.00]
139.50 [138.00, 141.00]
139.00 [137.00, 140.50]
139.00 [137.50, 141.00]
N/A
N/A
139.00 (2.77)
139.41 (2.68)
-0.15
...Missing; n (%)
13,657 (65.7%)
13,040 (62.8%)
27,735 (95.1%)
27,553 (94.5%)
N/A
N/A
41,392 (82.9%)
40,593 (81.3%)
0.04
Lab result number- Albumin mean (only >0 and <=10 
included)
                                             6,700                                              7,308                                              1,299                                              1,463 
N/A
N/A                                              7,999                                              8,771 
...mean (sd)
4.27 (0.32)
4.28 (0.32)
4.25 (0.46)
4.24 (0.58)
N/A
N/A
4.27 (0.35)
4.27 (0.38)
0.00
...median [IQR]
4.30 [4.10, 4.50]
4.30 [4.10, 4.50]
4.30 [4.10, 4.50]
4.30 [4.10, 4.50]
N/A
N/A
4.30 (0.35)
4.30 (0.38)
0.00
...Missing; n (%)
14,072 (67.7%)
13,464 (64.8%)
27,851 (95.5%)
27,687 (95.0%)
N/A
N/A
41,923 (84.0%)
41,151 (82.4%)
0.04
Lab result number- Glucose (fasting or random) mean 
(only 10-1000 included)
                                             7,121                                              7,744                                              1,371                                              1,522 
N/A
N/A                                              8,492                                              9,266 
...mean (sd)
170.54 (71.23)
163.02 (65.86)
172.40 (71.73)
164.90 (65.90)
N/A
N/A
170.84 (71.32)
163.33 (65.87)
0.11
...median [IQR]
152.00 [123.75, 198.33]
146.00 [120.00, 185.00]
156.00 [125.00, 200.50]
148.00 [121.38, 192.00]
N/A
N/A
152.65 (71.32)
146.33 (65.87)
0.09
...Missing; n (%)
13,651 (65.7%)
13,028 (62.7%)
27,779 (95.3%)
27,628 (94.8%)
N/A
N/A
41,430 (83.0%)
40,656 (81.4%)
0.04
Lab result number- Potassium mean (only 1-7 
included)
                                             7,219                                              7,828                                              1,482                                              1,636 
N/A
N/A                                              8,701                                              9,464 
...mean (sd)
4.42 (0.43)
4.40 (0.42)
4.38 (0.40)
4.39 (0.41)
N/A
N/A
4.41 (0.43)
4.40 (0.42)
0.02
...median [IQR]
4.40 [4.13, 4.70]
4.40 [4.10, 4.65]
4.40 [4.10, 4.60]
4.40 [4.10, 4.60]
N/A
N/A
4.40 (0.43)
4.40 (0.42)
0.00
...Missing; n (%)
13,553 (65.2%)
12,944 (62.3%)
27,668 (94.9%)
27,514 (94.4%)
N/A
N/A
41,221 (82.6%)
40,458 (81.0%)
0.04
Comorbidity Scores
CCI (180 days)- ICD9 and ICD10 
...mean (sd)
2.25 (1.79)
2.24 (1.79)
1.62 (1.51)
1.62 (1.50)
2.87 (2.04)
2.88 (2.07)
2.33 (1.83)
2.33 (1.84)
0.00
...median [IQR]
2.00 [1.00, 3.00]
2.00 [1.00, 3.00]
1.00 [1.00, 2.00]
1.00 [1.00, 2.00]
2.00 [1.00, 4.00]
2.00 [1.00, 4.00]
1.68 (1.83)
1.68 (1.84)
0.00
Frailty Score: Qualitative Version 365 days as 
Categories, 
...0; n (%)
8,392 (40.4%)
8,404 (40.5%)
10,050 (34.5%)
10,096 (34.6%)
9,086 (22.1%)
8,951 (21.8%)
27,528 (30.2%)
27,451 (30.1%)
0.00
...1 to 2; n (%)
7,972 (38.4%)
7,860 (37.8%)
13,116 (45.0%)
13,180 (45.2%)
15,015 (36.5%)
14,927 (36.3%)
36,103 (39.6%)
35,967 (39.5%)
0.00
...3 or more; n (%)
4,408 (21.2%)
4,508 (21.7%)
5,984 (20.5%)
5,874 (20.2%)
17,040 (41.4%)
17,263 (42.0%)
27,432 (30.1%)
27,645 (30.4%)
-0.01
Frailty Score: Empirical Version 365 days as 
Categories, 
...< 0.12908; n (%)
5,862 (28.2%)
6,186 (29.8%)
8,421 (28.9%)
8,678 (29.8%)
4,443 (10.8%)
4,810 (11.7%)
18,726 (20.6%)
19,674 (21.6%)
-0.02
...0.12908 - 0.1631167; n (%)
6,990 (33.7%)
6,791 (32.7%)
10,018 (34.4%)
9,960 (34.2%)
9,817 (23.9%)
9,685 (23.5%)
26,825 (29.5%)
26,436 (29.0%)
0.01
...>= 0.1631167; n (%)
7,920 (38.1%)
7,795 (37.5%)
10,711 (36.7%)
10,512 (36.1%)
26,881 (65.3%)
26,646 (64.8%)
45,512 (50.0%)
44,953 (49.4%)
0.01
Non-Frailty; n (%)
11,629 (56.0%)
11,843 (57.0%)
15,184 (52.1%)
15,193 (52.1%)
1,784 (4.3%)
1,488 (3.6%)
28,597 (31.4%)
28,524 (31.3%)
0.00
Frailty Score (mean): Qualitative Version 365 days, 
...mean (sd)
1.47 (1.87)
1.49 (1.90)
1.48 (1.71)
1.47 (1.68)
2.50 (2.34)
2.53 (2.36)
1.94 (2.05)
1.95 (2.06)
0.00
...median [IQR]
1.00 [0.00, 2.00]
1.00 [0.00, 2.00]
1.00 [0.00, 2.00]
1.00 [0.00, 2.00]
2.00 [1.00, 4.00]
2.00 [1.00, 4.00]
1.45 (2.05)
1.45 (2.06)
0.00
Frailty Score (mean): Empirical Version 365 days, 
...mean (sd)
0.15 (0.05)
0.15 (0.05)
0.15 (0.05)
0.15 (0.05)
0.19 (0.07)
0.19 (0.07)
0.17 (0.06)
0.17 (0.06)
0.00
...median [IQR]
0.14 [0.11, 0.17]
0.13 [0.11, 0.17]
0.14 [0.12, 0.17]
0.14 [0.12, 0.17]
0.18 [0.15, 0.23]
0.18 [0.15, 0.23]
0.16 (0.06)
0.16 (0.06)
0.00
Healthcare Utilization
Any hospitalization; n (%)
1,502 (7.2%)
1,425 (6.9%)
2,187 (7.5%)
2,073 (7.1%)
3,930 (9.6%)
3,921 (9.5%)
7,619 (8.4%)
7,419 (8.1%)
0.01
Any hospitalization within prior 30 days; n (%)
374 (1.8%)
352 (1.7%)
471 (1.6%)
428 (1.5%)
1,064 (2.6%)
1,044 (2.5%)
1,909 (2.1%)
1,824 (2.0%)
0.01
Any hospitalization during prior 31-180 days; n (%)
1,167 (5.6%)
1,121 (5.4%)
1,765 (6.1%)
1,706 (5.9%)
3,034 (7.4%)
3,095 (7.5%)
5,966 (6.6%)
5,922 (6.5%)
0.00
Endocrinologist Visit; n (%)
2,056 (9.9%)
1,969 (9.5%)
2,764 (9.5%)
2,681 (9.2%)
4,912 (11.9%)
4,908 (11.9%)
9,732 (10.7%)
9,558 (10.5%)
0.01
Endocrinologist Visit (30 days prior); n (%)
1,317 (6.3%)
1,266 (6.1%)
1,957 (6.7%)
1,885 (6.5%)
3,127 (7.6%)
3,017 (7.3%)
6,401 (7.0%)
6,168 (6.8%)
0.01
Endocrinologist Visit (31 to 180 days prior); n (%)
1,458 (7.0%)
1,377 (6.6%)
1,868 (6.4%)
1,813 (6.2%)
3,777 (9.2%)
3,709 (9.0%)
7,103 (7.8%)
6,899 (7.6%)
0.01
Internal medicine/family medicine visits; n (%)
16,288 (78.4%)
16,010 (77.1%)
25,399 (87.1%)
25,335 (86.9%)
35,174 (85.5%)
34,931 (84.9%)
76,861 (84.4%)
76,276 (83.8%)
0.02
Internal medicine/family medicine visits (30 days 
prior) ; n (%)
11,885 (57.2%)
11,951 (57.5%)
19,584 (67.2%)
19,656 (67.4%)
25,464 (61.9%)
25,427 (61.8%)
56,933 (62.5%)
57,034 (62.6%)
0.00
Internal medicine/family medicine visits (31 to 180 
days prior) ; n (%)
13,833 (66.6%)
13,782 (66.3%)
21,677 (74.4%)
21,565 (74.0%)
31,293 (76.1%)
31,269 (76.0%)
66,803 (73.4%)
66,616 (73.2%)
0.00
Cardiologist visit; n (%)
5,579 (26.9%)
5,471 (26.3%)
6,873 (23.6%)
6,760 (23.2%)
14,871 (36.1%)
14,709 (35.8%)
27,323 (30.0%)
26,940 (29.6%)
0.01
Number of Cardiologist visits (30 days prior); n (%)
1,938 (9.3%)
1,952 (9.4%)
2,477 (8.5%)
2,433 (8.3%)
5,195 (12.6%)
5,200 (12.6%)
9,610 (10.6%)
9,585 (10.5%)
0.00
Number of Cardiologist visits (31 to 180 days prior); 
n (%)
4,732 (22.8%)
4,630 (22.3%)
5,725 (19.6%)
5,657 (19.4%)
12,978 (31.5%)
12,880 (31.3%)
23,435 (25.7%)
23,167 (25.4%)
0.01
Electrocardiogram ; n (%)
6,245 (30.1%)
6,406 (30.8%)
8,940 (30.7%)
9,246 (31.7%)
14,823 (36.0%)
15,158 (36.8%)
30,008 (33.0%)
30,810 (33.8%)
-0.02
Table 1: Saxagliptin vs 2nd Generation Sulfonylureas

Use of glucose test strips; n (%)
876 (4.2%)
852 (4.1%)
1,297 (4.4%)
1,275 (4.4%)
1,535 (3.7%)
1,529 (3.7%)
3,708 (4.1%)
3,656 (4.0%)
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 ; n (%)
6,124 (29.5%)
6,035 (29.1%)
7,314 (25.1%)
7,406 (25.4%)
9,743 (23.7%)
9,800 (23.8%)
23,181 (25.5%)
23,241 (25.5%)
0.00
N antidiabetic drugs at index date 
...mean (sd)
1.83 (0.69)
1.84 (0.66)
1.87 (0.70)
1.87 (0.67)
1.81 (0.69)
1.81 (0.66)
1.83 (0.69)
1.84 (0.66)
-0.01
...median [IQR]
2.00 [1.00, 2.00]
2.00 [1.00, 2.00]
2.00 [1.00, 2.00]
2.00 [1.00, 2.00]
2.00 [1.00, 2.00]
2.00 [1.00, 2.00]
2.00 (0.69)
2.00 (0.66)
0.00
number of different/distinct medication 
prescriptions
...mean (sd)
9.09 (4.65)
9.01 (4.67)
9.07 (4.49)
9.01 (4.54)
10.17 (4.92)
10.14 (5.03)
9.57 (4.72)
9.52 (4.80)
0.01
...median [IQR]
8.00 [6.00, 12.00]
8.00 [6.00, 12.00]
8.00 [6.00, 11.00]
8.00 [6.00, 11.00]
9.00 [7.00, 13.00]
9.00 [7.00, 13.00]
8.45 (4.72)
8.45 (4.80)
0.00
Number of Hospitalizations
...mean (sd)
0.08 (0.33)
0.08 (0.33)
0.09 (0.33)
0.08 (0.32)
0.12 (0.43)
0.12 (0.42)
0.10 (0.38)
0.10 (0.37)
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 (0.38)
0.00 (0.37)
0.00
Number of hospital days
...mean (sd)
0.44 (2.40)
0.44 (2.26)
0.45 (2.24)
0.43 (2.33)
0.74 (3.54)
0.72 (3.58)
0.58 (2.93)
0.56 (2.95)
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 (2.93)
0.00 (2.95)
0.00
Number of Emergency Department (ED) visits 
...mean (sd)
0.30 (0.92)
0.28 (0.89)
0.12 (1.08)
0.11 (1.03)
0.49 (1.25)
0.48 (1.27)
0.33 (1.13)
0.32 (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 (1.13)
0.00 (1.12)
0.00
Number of Office visits
...mean (sd)
5.00 (4.34)
4.92 (3.86)
5.09 (4.75)
5.03 (3.99)
6.36 (5.21)
6.30 (4.81)
5.64 (4.88)
5.58 (4.35)
0.01
...median [IQR]
4.00 [2.00, 7.00]
4.00 [2.00, 6.00]
4.00 [2.00, 7.00]
4.00 [2.00, 6.25]
5.00 [3.00, 8.00]
5.00 [3.00, 8.00]
4.45 (4.88)
4.45 (4.35)
0.00
Number of Endocrinologist visits
...mean (sd)
0.52 (2.53)
0.49 (2.46)
0.47 (2.21)
0.52 (2.67)
0.76 (3.62)
0.81 (3.84)
0.61 (2.99)
0.64 (3.21)
-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 (2.99)
0.00 (3.21)
0.00
Number of internal medicine/family medicine visits
...mean (sd)
8.48 (13.64)
7.91 (12.09)
7.23 (9.90)
7.35 (9.32)
8.91 (11.47)
9.17 (11.81)
8.27 (11.54)
8.30 (11.14)
0.00
...median [IQR]
5.00 [1.00, 11.00]
5.00 [1.00, 11.00]
5.00 [2.00, 9.00]
5.00 [2.00, 10.00]
5.00 [2.00, 12.00]
6.00 [2.00, 12.00]
5.00 (11.54)
5.45 (11.14)
-0.04
Number of Cardiologist visits
...mean (sd)
1.35 (3.78)
1.35 (3.98)
1.07 (3.16)
1.07 (3.34)
2.05 (5.09)
2.03 (4.87)
1.58 (4.26)
1.57 (4.23)
0.00
...median [IQR]
0.00 [0.00, 1.00]
0.00 [0.00, 1.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 2.00]
0.00 [0.00, 2.00]
0.00 (4.26)
0.00 (4.23)
0.00
Number electrocardiograms received 
...mean (sd)
0.54 (1.19)
0.53 (1.15)
0.53 (1.12)
0.53 (1.08)
0.72 (1.37)
0.73 (1.35)
0.62 (1.25)
0.62 (1.22)
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]
0.00 [0.00, 1.00]
0.00 [0.00, 1.00]
0.00 (1.25)
0.00 (1.22)
0.00
Number of HbA1c tests ordered
...mean (sd)
1.26 (0.93)
1.25 (0.87)
1.04 (0.93)
1.03 (0.90)
1.43 (0.97)
1.42 (0.90)
1.27 (0.95)
1.26 (0.89)
0.01
...median [IQR]
1.00 [1.00, 2.00]
1.00 [1.00, 2.00]
1.00 [0.00, 2.00]
1.00 [0.00, 2.00]
1.00 [1.00, 2.00]
1.00 [1.00, 2.00]
1.00 (0.95)
1.00 (0.89)
0.00
Number of glucose tests ordered
...mean (sd)
0.49 (2.88)
0.48 (1.61)
0.42 (1.29)
0.41 (1.05)
0.51 (1.40)
0.51 (1.25)
0.48 (1.82)
0.47 (1.28)
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 (1.82)
0.00 (1.28)
0.00
Number of lipid tests ordered
...mean (sd)
1.09 (1.05)
1.09 (1.00)
0.98 (1.50)
0.97 (1.33)
1.13 (0.92)
1.14 (0.90)
1.07 (1.16)
1.07 (1.08)
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 (1.16)
1.00 (1.08)
0.00
Number of creatinine tests ordered
...mean (sd)
0.06 (0.37)
0.06 (0.33)
0.06 (0.39)
0.06 (0.33)
0.10 (0.43)
0.10 (0.41)
0.08 (0.40)
0.08 (0.37)
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 (0.40)
0.00 (0.37)
0.00
Number of BUN tests ordered
...mean (sd)
0.03 (0.29)
0.04 (0.27)
0.03 (0.29)
0.04 (0.28)
0.06 (0.34)
0.06 (0.33)
0.04 (0.31)
0.05 (0.30)
-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 (0.31)
0.00 (0.30)
0.00
Number of tests for microalbuminuria
...mean (sd)
0.71 (1.13)
0.72 (1.12)
0.53 (0.97)
0.53 (0.98)
0.48 (0.77)
0.48 (0.75)
0.55 (0.93)
0.55 (0.92)
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]
0.00 [0.00, 1.00]
0.00 [0.00, 1.00]
0.00 (0.93)
0.00 (0.92)
0.00
Total N distinct ICD9/ICD10 diagnoses at the 3rd 
digit level
...mean (sd)
3.44 (5.93)
3.43 (5.80)
1.11 (3.31)
1.08 (3.22)
4.03 (6.95)
4.01 (6.97)
2.96 (5.78)
2.94 (5.74)
0.00
...median [IQR]
0.00 [0.00, 5.00]
0.00 [0.00, 5.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 6.00]
0.00 [0.00, 6.00]
0.00 (5.78)
0.00 (5.74)
0.00
Use of thiazide; n (%)
2,083 (10.0%)
2,098 (10.1%)
2,947 (10.1%)
2,950 (10.1%)
5,096 (12.4%)
4,979 (12.1%)
10,126 (11.1%)
10,027 (11.0%)
0.00
Use of beta blockers; n (%)
7,279 (35.0%)
7,224 (34.8%)
10,647 (36.5%)
10,502 (36.0%)
19,033 (46.3%)
18,957 (46.1%)
36,959 (40.6%)
36,683 (40.3%)
0.01
Use of calcium channel blockers; n (%)
5,503 (26.5%)
5,572 (26.8%)
8,041 (27.6%)
7,927 (27.2%)
13,451 (32.7%)
13,548 (32.9%)
26,995 (29.6%)
27,047 (29.7%)
0.00
Table 1: Saxagliptin vs 2nd Generation Sulfonylureas