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

Replication of Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes (LEADER trial)
NCT03936049
May 27, 2021

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 
Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes (LEADER trial) 
 
1.2 Intended aim(s) 
 
The primary hypothesis was that liraglutide would be noninferior to placebo (plus standard of care) with regard to the 
primary outcome, with a margin of 1.30 for the upper boundary of the 95% confidence interval of the hazard ratio. 
 
1.3 Primary endpoint for replication and RCT finding 
Composite of Cardiovascular Death, Non-fatal Myocardial Infarction, or Non-fatal Stroke 
 
1.4 Required power for primary endpoint and noninferiority margin (if applicable) 
90% power and noninferiority margin of hazard ratio of 1.30 
 
1.5 Primary trial estimate targeted for replication 
 
HR = 0.87 (95% CI 0.78-0.97) comparing liraglutide to placebo (Marso et al.) 
 
 
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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4. Study Design Diagram 
The study design diagram visualizes key aspects of the longitudinal study design for expedited review. 
 

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 liraglutide to the DPP4 inhibitor (DPP4i) antidiabetic 
class as a proxy for placebo. Both 2nd generation sulfonylureas (SUs) and DPP4is are not known to have an impact on the outcome of 
interest. The comparison against DPP4i is the primary comparison. Initiators of 2nd generation SUs are used as a secondary 
comparator group. The patients will be required to have continuous enrollment during the baseline period of 180 days before 
initiation of liraglutide 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 liraglutide in the U.S. started on January 20, 2010. 
• For Marketscan: January 20, 2010-Dec 31, 2017 (end of data availability).  
• For Medicare: Jan 1, 2012-Dec 31, 2017 (start- end of data availability). 
• For Optum: January 20, 2010-March 31, 2019 (end of data availability). 
 
5.2.2 Specify inclusion/exclusion criteria for cohort entry and define the index date 
 
Inclusion and exclusion criteria were adapted from the trial as closely as possible. Definitions for all inclusion/exclusion are provided 
in Appendix A and are summarized in the flowcharts below.   
 
5.3 Flowchart of the study cohort assembly 
 
• For Liraglutide vs DPP4i 
  
Optum 
Marketscan 
Medicare* 
  
Less 
Excluded 
Patients 
Remaining 
Patients 
Less 
Excluded 
Patients 
Remaining 
Patients 
Less 
Excluded 
Patients 
Remaining 
Patients 

Effectiveness research with Real World Data to support FDA’s regulatory decision making: Protocol Template 
 
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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 
-74,012,464 
852,420 
-
190,638,745 
1,351,290 
-21,492,649 
1,973,526 
Patients who have continuous 6 months registration in the database  
-111,929 
740,491 
-134,586 
1,216,704 
-516,146 
1,457,380 
Patients without prior use of reference 
-394,596 
345,895 
-710,577 
506,127 
-754,558 
702,822 
Patients without prior use of exposure 
-112,350 
233,545 
-193,164 
312,963 
-102,088 
600,734 
Excluded because patient qualified in >1 exposure category 
-75 
233,470 
-138 
312,825 
-48 
600,686 
Patients who did not have missing age information 
-10 
233,460 
0 
312,825 
0 
600,686 
Patients who did not have missing gender information 
-16 
233,444 
0 
312,825 
0 
600,686 
Excluded based on Inclusion 1- DM Type 2 
-10,665 
222,779 
-29,308 
283,517 
-4,803 
595,883 
Excluded based on Inclusion 3- Either Prior cardiovascular disease cohort or No 
Prior cardiovascular disease group 
-42,768 
180,011 
-98,418 
185,099 
-17,351 
578,532 
Excluded based on Exclusion 1- Type 1 diabetes 
-3,952 
176,059 
-4,538 
180,561 
-14,315 
564,217 
Excluded based on Exclusion 2- Use of GLP1 or Pramlintide or DPP4i within 3 
months prior to index 
-953 
175,106 
-963 
179,598 
-1,652 
562,565 
Excluded based on Exclusion 3-Long Acting Insulin in prior 90 days 
-7,143 
167,963 
-5,629 
173,969 
-21,421 
541,144 
Excluded based on Exclusion 4-Diabetic ketoacidosis in prior 90 days 
-112 
167,851 
-84 
173,885 
-359 
540,785 
Excluded based on Exclusion 5- An acute coronary or cerebrovascular event in 
the previous 14 days 
-546 
167,305 
-720 
173,165 
-1,764 
539,021 
Excluded based on Exclusion 7- Oxygen canister use as a proxy for NYHA class 
IV 
-286 
167,019 
-297 
172,868 
-1,919 
537,102 
Excluded based on Exclusion 8- Current continuous renal replacement 
therapy/ESRD 
-437 
166,582 
-333 
172,535 
-2,110 
534,992 
Excluded based on Exclusion 10- Liver disease 
-2,572 
164,010 
-1,845 
170,690 
-7,745 
527,247 
Excluded based on Exclusion 11- Organ Transplant 
-83 
163,927 
-107 
170,583 
-188 
527,059 
Excluded based on Exclusion 12- History of Malignant Neoplasm in previous 5 
years and Exclusion 13- Family or personal history of multiple endocrine 
neoplasia type 2 (MEN2) or familial medullary thyroid carcinoma (FMTC) 
-5,878 
158,049 
-5,403 
165,180 
-24,286 
502,773 
Excluded based on Exclusion 14- Personal history of non-familial medullary 
thyroid carcinoma 
0 
158,049 
0 
165,180 
0 
502,773 
Excluded based on Exclusion 17- Drug abuse or dependence 
-450 
157,599 
-164 
165,016 
-878 
501,895 
Excluded based on Exclusion 20- Contraception or pregnancy 
-357 
157,242 
-511 
164,505 
-1002 
500,893 

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Final cohort 
  
157,242 
  
164,505 
  
500,893 
* Medicare database includes only patients with at least one diagnosis for diabetes, heart failure, or cerebrovascular disease. 
 
 
• For Liraglutide vs 2nd Gen. SUs 
  
Optum 
Marketscan 
Medicare* 
  
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 
-73,337,305 
1,527,579 
-
189,889,741 
2,100,294 
-19,968,954 
3,497,221 
Patients who have continuous 6 months registration in the database  
-204,156 
1,323,423 
-233,189 
1,867,105 
-952,050 
2,545,171 
Patients without prior use of reference 
-888,112 
435,311 
-1,294,078 
573,027 
-1,703,970 
841,201 
Patients without prior use of exposure 
-103,834 
331,477 
-177,643 
395,384 
-95,982 
745,219 
Excluded because patient qualified in >1 exposure category 
-138 
331,339 
-236 
395,148 
-85 
745,134 
Patients who did not have missing age information 
-14 
331,325 
0 
395,148 
0 
745,134 
Patients who did not have missing gender information 
-26 
331,299 
0 
395,148 
0 
745,134 
Excluded based on Inclusion 1- DM Type 2 
-24,242 
307,057 
-58,280 
336,868 
-10,070 
735,064 
Excluded based on Inclusion 3- Either Prior cardiovascular disease cohort or No 
Prior cardiovascular disease group 
-62,008 
245,049 
-130,017 
206,851 
-24,553 
710,511 
Excluded based on Exclusion 1- Type 1 diabetes 
-4,763 
240,286 
-5,243 
201,608 
-15,909 
694,602 
Excluded based on Exclusion 2- Use of GLP1 or Pramlintide or DPP4i within 3 
months prior to index 
-7,666 
232,620 
-8,727 
192,881 
-23,001 
671,601 
Excluded based on Exclusion 3-Long Acting Insulin in prior 90 days 
-6,604 
226,016 
-5,151 
187,730 
-19,399 
652,202 
Excluded based on Exclusion 4-Diabetic ketoacidosis in prior 90 days 
-169 
225,847 
-151 
187,579 
-442 
651,760 
Excluded based on Exclusion 5- An acute coronary or cerebrovascular event in 
the previous 14 days 
-806 
225,041 
-1,218 
186,361 
-2,112 
649,648 
Excluded based on Exclusion 7- Oxygen canister use as a proxy for NYHA class 
IV 
-3,508 
221,533 
-2,257 
184,104 
-3,451 
646,197 

Effectiveness research with Real World Data to support FDA’s regulatory decision making: Protocol Template 
 
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Excluded based on Exclusion 8- Current continuous renal replacement 
therapy/ESRD 
-710 
220,823 
-674 
183,430 
-3,666 
642,531 
Excluded based on Exclusion 10- Liver disease 
-3,303 
217,520 
-2,124 
181,306 
-9,653 
632,878 
Excluded based on Exclusion 11- Organ Transplant 
-105 
217,415 
-143 
181,163 
-263 
632,615 
Excluded based on Exclusion 12- History of Malignant Neoplasm in previous 5 
years and Exclusion 13- Family or personal history of multiple endocrine 
neoplasia type 2 (MEN2) or familial medullary thyroid carcinoma (FMTC) 
-7,050 
210,365 
-6,342 
174,821 
-28,690 
603,925 
Excluded based on Exclusion 14- Personal history of non-familial medullary 
thyroid carcinoma 
0 
210,365 
0 
174,821 
0 
603,925 
Excluded based on Exclusion 17- Drug abuse or dependence 
-638 
209,727 
-226 
174,595 
-1119 
602,806 
Excluded based on Exclusion 20- Contraception or pregnancy 
-371 
209,356 
-453 
174,142 
-967 
601,839 
Final cohort 
  
209,356 
  
174,142 
  
601,839 
* 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 liraglutide. Initiation will be defined by no use of liraglutide or a comparator in the prior 
6 months before treatment initiation (washout period).  
 
Comparator agents: 
• Initiators of liraglutide will be compared to initiators of- 
o DPP4i (primary) 
o 2nd generation sulfonylureas 
 
Because liraglutide and comparators are frequently used as second or third line treatments of T2DM, we expect it to be unlikely that 
liraglutide and comparators are initiated in patients with substantially different baseline risk for proposed outcomes.  
 
6.2 Preliminary covariates: 

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• Age 
• Sex 
• Combined Comorbidity Index (CCI), measured over the default baseline covariate assessment period, defined as 180 days 
prior to and including index date 
 
Covariates listed above represent only a small subset of covariates that will ultimately be controlled for in the design and analysis. 
We use the covariates above only for initial feasibility analyses to judge whether there is likely to be sufficient overlap between 
treatment groups to proceed with the study. Remaining covariates are defined only after the study has passed the initial feasibility 
analysis and the initial power assessment and are listed in Table 1 (Appendix B). These covariates are based on those used by 
Patorno et al. (2019). 
 
6.3 Outcome variables and study follow-up:  
 
6.3.1 Outcome variables 
 
Effectiveness outcomes of interest (definitions provided in Appendix A):  
 
• 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 individual component, fatal MI is included) 
o Hospital admission for stroke (for purposes of 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. For comparison with 2nd Gen. SUs: Severe hypoglycemia (we expect to see protective effect; American Diabetes Association, 
2018) 

Effectiveness research with Real World Data to support FDA’s regulatory decision making 
 
 
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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 
liraglutide 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: 
• For Liraglutide vs 2nd generation SUs 
Optum: https://bwh-dope.aetion.com/#/projects/details/632/results/30594/result/0  
Marketscan: https://bwh-dope.aetion.com/#/projects/details/633/results/30595/result/0  
Medicare: https://bwh-dope.aetion.com/#/projects/details/634/results/30593/result/0  
 
• For Liraglutide vs DPP4i 
Optum: https://bwh-dope.aetion.com/#/projects/details/632/results/30606/result/0  
Marketscan: https://bwh-dope.aetion.com/#/projects/details/633/results/30607/result/0  
Medicare: https://bwh-dope.aetion.com/#/projects/details/634/results/30605/result/0  
 
Date conducted: rerun on Jan 27, 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 
 
 

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8. Initial Power Assessment 
 
Aetion report name: 
• For Liraglutide vs 2nd SUs 
Optum: https://bwh-dope.aetion.com/#/projects/details/632/results/30597/result/1  
Marketscan: https://bwh-dope.aetion.com/#/projects/details/633/results/30596/result/1  
Medicare: https://bwh-dope.aetion.com/#/projects/details/634/results/30598/result/1  
 
• For Liraglutide vs DPP4i 
Optum: https://bwh-dope.aetion.com/#/projects/details/632/results/30608/result/1  
Marketscan: https://bwh-dope.aetion.com/#/projects/details/633/results/30609/result/1    
Medicare: https://bwh-dope.aetion.com/#/projects/details/634/results/30610/result/1  
 
Date conducted: rerun on Jan 27, 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: 
David Martin 
Date reviewed: 
1/10/19 
Reasons for stopping 
analysis (if required): 
 
 
 
9. Balance Assessment after PS matching 
 

Effectiveness research with Real World Data to support FDA’s regulatory decision making 
 
 
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Aetion report name: 
• For Liraglutide vs 2nd Gen. SUs 
Optum: https://bwh-dope.aetion.com/projects/details/632/results/44783/result/0 
Marketscan: https://bwh-dope.aetion.com/projects/details/633/results/45436/result/0 
Medicare: https://bwh-dope.aetion.com/projects/details/634/results/45432/result/0 
 
• For Liraglutide vs DPP4i 
Optum: https://bwh-dope.aetion.com/projects/details/632/results/44786/result/0 
Marketscan: https://bwh-dope.aetion.com/projects/details/633/results/44787/result/0 
Medicare: https://bwh-dope.aetion.com/projects/details/634/results/45433/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. 
o For Liraglutide vs DPP4i 
  
Overall 
Referent 
Exposure 
Dummy Outcome 
0 (0.00%) 
0 (0.00%) 
0 (0.00%) 
Death 
1,271 (0.75%) 
827 (0.98%) 
444 (0.53%) 
Start of an additional exposure 
4,700 (2.79%) 
1,913 (2.27%) 
2,787 (3.30%) 

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End of index exposure 
99,981 (59.27%) 
45,078 (53.44%) 
54,903 (65.09%) 
Specified date reached 
29,951 (17.76%) 
16,708 (19.81%) 
13,243 (15.70%) 
End of patient enrollment 
22,798 (13.51%) 
12,483 (14.80%) 
10,315 (12.23%) 
Switch to other SUs (for censoring) + nursing home admission 
9,989 (5.92%) 
7,336 (8.70%) 
2,653 (3.15%) 
 
o For Liraglutide vs 2nd Gen. SUs 
  
Overall 
Referent 
Exposure 
Dummy Outcome 
0 (0.00%) 
0 (0.00%) 
0 (0.00%) 
Death 
858 (0.79%) 
595 (1.10%) 
263 (0.49%) 
Start of an additional exposure 
4,294 (3.96%) 
967 (1.78%) 
3,327 (6.14%) 
End of index exposure 
61,038 (56.33%) 
27,098 (50.01%) 
33,940 (62.64%) 
Specified date reached 
21,830 (20.15%) 
13,222 (24.40%) 
8,608 (15.89%) 
End of patient enrollment 
14,181 (13.09%) 
7,902 (14.58%) 
6,279 (11.59%) 
Switch to other SUs (for censoring) + nursing home admission 
6,163 (5.69%) 
4,398 (8.12%) 
1,765 (3.26%) 
 
• Report follow-up time by treatment group. 
o For Liraglutide vs DPP4i 
 
Median Follow-Up Time (Days) [IQR] 
Patient Group 
Optum 
Marketscan 
Medicare 
Overall Patient Population 
157 [88-334] 
185 [91-413] 
179 [92-381] 
Referent 
173 [88-368] 
209 [112-437] 
209 [112-437] 
Exposure 
148 [88-302] 
159 [88-331] 
159 [88-331] 
 
o For Liraglutide vs 2nd Gen. SUs 
 
Median Follow-Up Time (Days) [IQR] 
Patient Group 
Optum 
Marketscan 
Medicare 
Overall Patient Population 
154 [88-339] 
168 [88-379] 
179 [98-397] 
Referent 
181 [100-407] 
231 [128-500] 
231 [128-500] 
Exposure 
148 [88-279] 
148 [88-307] 
148 [88-307] 
 

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• Report risk per 1,000 patients 
o For Liraglutide vs DPP4i 
  
Optum 
Marketscan 
Medicare 
Risk per 1,000 patients 
14.30 
12.11 
38.60 
 
o For Liraglutide vs 2nd Gen. SUs 
  
Optum 
Marketscan 
Medicare 
Risk per 1,000 patients 
18.97 
22.54 
48.79 
 
Aetion report name: 
• For Liraglutide vs 2nd Gen. SUs 
Optum: https://bwh-dope.aetion.com/#/projects/details/632/results/34412/result/0 
Marketscan: https://bwh-dope.aetion.com/#/projects/details/633/results/34413/result/0 
Medicare: https://bwh-dope.aetion.com/#/projects/details/634/results/34414/result/0 
 
• For Liraglutide vs DPP4i 
Optum: https://bwh-dope.aetion.com/#/projects/details/632/results/34415/result/0 
Marketscan: https://bwh-dope.aetion.com/#/projects/details/633/results/34416/result/0 
Medicare: https://bwh-dope.aetion.com/#/projects/details/634/results/34417/result/0 
 
Date conducted: 04/25/2019 
 
 
 
10. Final Power Assessment 
 
Date conducted: 12/01/2019 
 
• Re-calculate power in the appropriate excel table, using the revised number of matched patients from the PS-match in Section 9. 
All other parameters in the table should be the same as in Section 8. If the study is to be implemented in more than one 
database, copy and paste excel sheet to report power for each database separately and for the pooled analysis that uses data 

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from all databases together. Power calculations are based on the formulas from Chow et al. (2008). 
 
o For Liraglutide vs DPP4i 
§ Pooled 
 
 
§ Optum 
Superiority Analysis
Number of patients matched
Reference
84,345
Exposed
84,345
Risk per 1,000 patients
21.67
Desired HR from RCT
0.87
Alpha (2-sided)
0.05
Number of events expected
3655.5123
Power
0.987775093
Non-inferiority Analysis
Number of patients matched
Reference
84,345
Exposed
84,345
Risk per 1,000 patients
21.67
Assumed HR from RCT
1
Alpha (2-sided)
0.05
Non-inferiority margin
1.3
Number of events expected
3655.5123
Power
0.999999999

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§ Marketscan 
 
 
§ Medicare 
Superiority Analysis
Number of patients matched
Reference
19,187
Exposed
19,187
Risk per 1,000 patients
14.30
Desired HR from RCT
0.87
Alpha (2-sided)
0.05
Number of events expected
548.7482
Power
0.371306397
Non-inferiority Analysis
Number of patients matched
Reference
19,187
Exposed
19,187
Risk per 1,000 patients
14.30
Assumed HR from RCT
1
Alpha (2-sided)
0.05
Non-inferiority margin
1.3
Number of events expected
548.7482
Power
0.867151513
Superiority Analysis
Number of patients matched
Reference
20,777
Exposed
20,777
Risk per 1,000 patients
12.11
Desired HR from RCT
0.87
Alpha (2-sided)
0.05
Number of events expected
503.21894
Power
0.345542948
Non-inferiority Analysis
Number of patients matched
Reference
20,777
Exposed
20,777
Risk per 1,000 patients
12.11
Assumed HR from RCT
1
Alpha (2-sided)
0.05
Non-inferiority margin
1.3
Number of events expected
503.21894
Power
0.837143294

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o For Liraglutide vs 2nd Gen. SUs 
§ Pooled 
 
 
§ Optum 
Superiority Analysis
Number of patients matched
Reference
44,381
Exposed
44,381
Risk per 1,000 patients
38.60
Desired HR from RCT
0.87
Alpha (2-sided)
0.05
Number of events expected
3426.2132
Power
0.982819492
Non-inferiority Analysis
Number of patients matched
Reference
44,381
Exposed
44,381
Risk per 1,000 patients
38.60
Assumed HR from RCT
1
Alpha (2-sided)
0.05
Non-inferiority margin
1.3
Number of events expected
3426.2132
Power
0.999999995
Superiority Analysis
Number of patients matched
Reference
54,182
Exposed
54,182
Risk per 1,000 patients
30.10
Desired HR from RCT
0.87
Alpha (2-sided)
0.05
Number of events expected
3261.7564
Power
0.978141227
Non-inferiority Analysis
Number of patients matched
Reference
54,182
Exposed
54,182
Risk per 1,000 patients
30.1
Assumed HR from RCT
1
Alpha (2-sided)
0.05
Non-inferiority margin
1.3
Number of events expected
3261.7564
Power
0.999999984

Effectiveness research with Real World Data to support FDA’s regulatory decision making 
 
 
17 
 
 
§ Marketscan 
 
 
 
§ Medicare 
Superiority Analysis
Number of patients matched
Reference
12,253
Exposed
12,253
Risk per 1,000 patients
18.97
Desired HR from RCT
0.87
Alpha (2-sided)
0.05
Number of events expected
464.87882
Power
0.323513047
Non-inferiority Analysis
Number of patients matched
Reference
12,253
Exposed
12,253
Risk per 1,000 patients
18.97
Assumed HR from RCT
1
Alpha (2-sided)
0.05
Non-inferiority margin
1.3
Number of events expected
464.87882
Power
0.807428816
Superiority Analysis
Number of patients matched
Reference
13,591
Exposed
13,591
Risk per 1,000 patients
22.54
Desired HR from RCT
0.87
Alpha (2-sided)
0.05
Number of events expected
612.68228
Power
0.406665538
Non-inferiority Analysis
Number of patients matched
Reference
13,591
Exposed
13,591
Risk per 1,000 patients
22.54
Assumed HR from RCT
1
Alpha (2-sided)
0.05
Non-inferiority margin
1.3
Number of events expected
612.68228
Power
0.900972235

Effectiveness research with Real World Data to support FDA’s regulatory decision making: Protocol Template 
 
18 
 
 
• Stop analyses until balance and final power assessment are reviewed by primary investigators, FDA, and assigned members of 
advisory board. Reviewers evaluate the results of the analyses described above in Sections 9 and 10, including numbers of 
patients, balance in patient characteristics, follow-up time, and reasons for censoring by treatment group, as well as overall rates 
of outcomes and study power. 
Reviewed by PI: 
Jessica Franklin 
Date reviewed: 
12/9/19 
Reviewed by FDA: 
David Martin 
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 
Superiority Analysis
Number of patients matched
Reference
28,338
Exposed
28,338
Risk per 1,000 patients
48.79
Desired HR from RCT
0.87
Alpha (2-sided)
0.05
Number of events expected
2765.22204
Power
0.955585785
Non-inferiority Analysis
Number of patients matched
Reference
28,338
Exposed
28,338
Risk per 1,000 patients
48.79
Assumed HR from RCT
1
Alpha (2-sided)
0.05
Non-inferiority margin
1.3
Number of events expected
2765.22204
Power
0.999999606

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

Effectiveness research with Real World Data to support FDA’s regulatory decision making: Protocol Template 
 
20 
14.1 
Results from primary and secondary analyses: 
 
Separately for each endpoint and each comparator group: 
Analysis 
No. exposed events 
No. referent events 
Exposed rate 
Referent rate 
HR (95% CI) 
Crude 
 
 
 
 
 
Primary analysis 
 
 
 
 
 
Analysis 2 
 
 
 
 
 
... 
 
 
 
 
 
HR, Hazard Ratio; CI, Confidence Interval. 
 
15. References 
 
 
American Diabetes Association. 8. Pharmacologic Approaches to Glycemic Treatment: Standards of Medical Care in Diabetes-2018. 
Diabetes Care. 2018;41(Suppl 1):S73-S85. doi:10.2337/dc18-S008. 
 
Chow S, Shao J, Wang H. 2008.  Sample Size Calculations in Clinical Research. 2nd Ed. Chapman & Hall/CRC Biostatistics Series. page 
177 
 
Marso SP, Daniels GH, Brown-Frandsen K, Kristensen P, Mann JF, Nauck MA, Nissen SE, Pocock S, Poulter NR, Ravn LS, Steinberg WM. 
Liraglutide and cardiovascular outcomes in type 2 diabetes. New England Journal of Medicine. 2016; 375(4):311-22. 
 
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)  
 
 

# 
LEADER trial definitions 
Implementation in routine care
References/Rationale
Color coding
Liraglutide versus placebo
Liraglutide vs. DPP4i or 2nd generation sulfonylurea 
Criteria
Adequate mapping in claims
The primary composite outcome in the time-to-event analysis was the first occurrence of death from cardiovascular causes, nonfatal 
myocardial infarction, or nonfatal stroke. HR = 0.87 (95% CI 0.78-0.97)
Measured 1 days after drug initiation in diagnosis position specified below and inpatient care 
setting:
Inpatient mortality/MI/Stroke --
For MI
Any diagnosis position in inpatient care setting
ICD-9 Dx 410.X (acute myocardial infarction) excluding 410.x2 (subsequent episode of care), 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.]
Intermediate mapping in 
claims
Poor mapping or cannot be 
measured in claims 
1 Men or women with type 2 diabetes
Measured 180 days prior to drug initiation in any diagnosis position and inpatient or outpatient 
care setting
 T2DM (ICD-9 Dx code of 250.x0 or 250.x2; ICD-10 Dx code of E11.x)
Patorno, Elisabetta et al. "Cardiovascular outcomes associated with canagliflozin 
versus other non-gliflozin antidiabetic drugs: population based cohort study." 
BMJ 2018;360:k119 http://dx.doi.org/10.1136/bmj.k119
Patorno, Elisabetta et al. "Empagliflozin and the Risk of Heart Failure 
Hospitalization in Routine Clinical Care: A First Analysis from the Empagliflozin 
Comparative Effectiveness and Safety (EMPRISE) Study."  Circulation. 2019 Apr 8. 
doi: 10.1161/CIRCULATIONAHA.118.039177
Can't be measured in claims 
but not important for the 
analysis
2 Anti-diabetic drug naïve or treated with one or more oral anti-diabetic drugs or treated with human NPH insulin or long-acting insulin 
analogue or premixed insulin, alone or in combination with OAD(s)
N/A (this is basically anyone)
3 Either of the following:
• Prior cardiovascular disease: Age ≥ 50 years at screening, AND at least one of the following:
 Age ≥ 50  at drug initiation AND
o Prior MI
Measured 180 days prior to drug initiation in any diagnosis position and inpatient or outpatient 
care setting
Acute MI: 410.xx, Old MI: 412.xx
o Prior stroke or TIA
Measured 180 days prior to drug initiation in any diagnosis position and inpatient or outpatient 
care setting
Stroke or TIA ICD-9 Dx: 430.xx, 431.xx, 433.xx, 434.xx, 435.xx, 436.xx
INCLUSION 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
Please see the following Google Drive for further details or any missing information: 
https://drive.google.com/drive/folders/1WD618wrywYjEaXzfLTcuK-VCcnb6b-gV?usp=sharing
PRIMARY OUTCOME
Trial details- Secondary indication, 4a- unintended superiority with label change 
EXPOSURE vs. COMPARISON
Appendix A

o Prior coronary, carotid or peripheral arterial revascularization
Measured 180 days prior to drug initiation in any diagnosis position and care setting as defined 
below:
Coronary revascularization (PTCA, stenting, CABG) 
PTCA:
Inpatient CPT-4: 92973, 92982, 92984, 92995, 92996, 92920 – 92921, 92924 – 92925, 92937, 
92938, 92941, 92943, 92944
OR –
Inpatient or outpatient ICD-9 procedure: 00.66, 36.01, 36.02, 36.03, 36.05, 36.09
Stenting:
Inpatient CPT-4:  92980, 92981, 92928 – 92929, 92933 - 92934
OR –
Inpatient or outpatient ICD-9 procedure: 36.06, 36.07
CABG:
Inpatient CPT-4: 33510 – 33536, 33545, 33572. 
       OR – 
Inpatient or outpatient ICD-9 procedure: 36.1x, 36.2x
Transmyocardial revascularization: Inpatient CPT-4: 33140, 33141 OR - Inpatient ICD-9 
procedure: 36.31-36.34
o >50% stenosis of coronary, carotid, or lower extremity arteries
Measured 180 days prior to drug initiation in any diagnosis position and inpatient or outpatient 
care setting
414.x ,
Peripheral vascular disease
ICD9 diagnosis:
440.20 – 440.24, 440.29 – 440.32,  440.3, 440.4, 443.9  
o History of symptomatic CHD documented by positive exercise stress test or any cardiac imaging or unstable angina with ECG changes
N/A
o Asymptomatic cardiac ischemia documented by positive nuclear imaging test, exercise test or dobutamine stress echo
N/A
o Chronic heart failure NYHA class II-III
Measured 180 days prior to drug initiation in any diagnosis position and inpatient or outpatient 
care setting
 ICD-9 diagnosis 
428.x, 398.91, 402.01, 402.11, 402.91, 404.01, 404.11, 404.91, 404.03, 404.13, 404.93
o Chronic renal failure:
– eGFR <60 mL/min/1.73m2 (Modification of Diet in Renal Disease formula)
– eGFR <60 mL/min (Cockcroft-Gault formula)
• No Prior cardiovascular disease: Age ≥ 60 years at screening, AND at least one of the following:
 Age ≥ 60  at drug initiation AND
o Microalbuminuria or proteinuria
Measured 180 days prior to drug initiation in any diagnosis position and inpatient or outpatient 
care setting
Proteinuria ICD 9 DX
791.0
ICD10 DX
R80.X
Albumin abnormality ICD9 Dx- 790.99
ICD10 Dx - R77.0 
o Hypertension and left ventricular hypertrophy by ECG or imaging
Measured 180 days prior to drug initiation in any diagnosis position and with 1 inpatient care 
setting claim AND 2 outpatient care setting claims:
Hypertension  any ICD-9 code from 401.x – 405.x 
o Left ventricular systolic or diastolic dysfunction by imaging
N/A
o Ankle-brachial index <0.9
Measured 180 days prior to drug initiation in any diagnosis position and inpatient or outpatient 
care setting
ICD-9 440.21
4 HbA1c ≥ 7.0% at screening
N/A
1
Type 1 diabetes
Measured 180 days prior to drug initiation in any diagnosis position and inpatient or outpatient 
care setting
DM type 1- At least 1 inpatient or outpatient ICD-9 Dx code of 250.x1 or 250.x3 or ICD-10 Dx 
code of E10.x in the 6 months prior to drug initiation. 
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 Use of a GLP-1 receptor agonist (exenatide, liraglutide or other) or pramlintide or any (dipeptidyl peptidase 4 (DPP-4) inhibitor within the 3 
months prior to screening
Dispensing of at least one of the following medications in the 90 days prior to drug initiation:
Use of a GLP-1 receptor agonist (exenatide, liraglutide or other) or pramlintide or any (dipeptidyl 
peptidase 4 (DPP-4) inhibitor within the 3 months prior to index date (Please see AHA therapy 
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
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
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
Measured 180 days prior to drug initiation in any diagnosis position and inpatient or outpatient 
care setting
CKD stage 3-6
585.3x-585.6x
3a
3b
EXCLUSION CRITERIA
Appendix A

3 Use of insulin other than human neutral protamine hagedorn (NPH) insulin or long-acting insulin analogue within 3 months prior to 
screening. Short-term use of other insulin during this period in connection with intercurrent illness is allowed at Investigator’s discretion
Use of long-term insulin in 90 days prior to drug initiation defined as a claim for dispensing of 
insulin (Please see AHA therapy sheet for insulin).
4
Acute decompensation of glycemic control requiring immediate intensification of treatment to prevent acute complications of diabetes 
(e.g., diabetic ketoacidosis) in the previous 3 months
Measured 90 days prior to drug initiation in any diagnosis position and inpatient or outpatient 
care setting
Diabetic ketoacidosis ICD-9 Diagnosis 250.1x
Bobo WV, Cooper WO, Epstein RA, Jr., Arbogast PG, Mounsey J, Ray WA. Positive 
predictive value of automated database records for diabetic ketoacidosis (DKA) 
in children and youth exposed to antipsychotic drugs or control medications: a 
Tennessee Medicaid Study. BMC medical research methodology 2011;11:157
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
An acute coronary or cerebrovascular event in the previous 14 days
Measured 14 days prior to drug initiation in any diagnosis/procedure position and inpatient 
care setting
MI, stroke, revascularization, PTCA, CABG:
Acute MI  ICD-9  diagnosis 410.xx 
Coronary revascularization- PTCA:
Inpatient CPT-4: 92973, 92982, 92984, 92995, 92996, 92920 – 92921, 92924 – 92925, 92937, 
92938, 92941, 92943, 92944 – OR – Inpatient ICD-9 procedure: 00.66, 36.01, 36.02, 36.03, 
36.05, 36.09
Stenting:
Inpatient CPT-4:  92980, 92981, 92928 – 92929, 92933 - 92934 –  OR – Inpatient ICD-9 
procedure: 36.06, 36.07
Transmyocardial revascularization
CPT-4: 33140, 33141 –  OR – Inpatient ICD-9 procedure: 36.31-36.34
CABG:
Inpatient CPT-4: 33510 – 33536, 33545, 33572 –  OR –  Inpatient ICD-9 procedure: 36.1x, 36.2x
Stroke ICD-9 diagnosis :
430.xx  Subarachnoid hemorrhage (SAH)
431.xx  Intracerebral hemorrhage (ICH)
433.x1  Occlusion and stenosis of precerebral arteries with cerebral infarction
434.x1  Occlusion and stenosis of cerebral arteries with cerebral infarction
436.x  Acute, but ill-defined cerebrovascular events
6 Currently planned coronary, carotid or peripheral artery revascularization
N/A
7
Chronic heart failure NYHA class IV
Measured 180  days prior to drug initiation in any diagnosis/procedure position and inpatient 
or outpatient care setting
Oxygen use codes: 
HCPCS: E0424 E0425 E0430 E0431 E0433 E0434 E0435 E0439 E0440 E0441 E0442 E0443 E0444 
E0447 E1390 E1391 E1392 E1405 E1406 K0738 S8120 S8121
or
ICD-10 : Dependence on Supplemental oxygen Z99.81
ICD-9: Other dependence on machines, supplemental oxygen V46.2
ORIGINAL DEFINITION: Inpatient Heart failure (CHF) in prior 60 days
Any of ICD-9 codes : 428.x, 398.91, 402.01, 402.11, 402.91, 404.01, 404.11, 
404.91, 404.03, 404.13, 404.93
NEW DEFINITION 4/22/2019:
Inpatient diagnosis may not be specific enough for including severe 
symptomatic class IV patients.  Therefore, we decided to incorporate the use of 
oxygen therapy (not limited to inpatient setting). 
8
Current continuous renal replacement therapy
Measured 180 days prior to drug initiation in any procedure position and inpatient or 
outpatient care setting:
ESRD (Please see ESRD codes tab for codes and algorithm used to define ESRD and Renal 
Transplant)
Patorno, Elisabetta et al. "Cardiovascular outcomes associated with canagliflozin 
versus other non-gliflozin antidiabetic drugs: population based cohort study." 
BMJ 2018;360:k119 http://dx.doi.org/10.1136/bmj.k119
Patorno, Elisabetta et al. "Empagliflozin and the Risk of Heart Failure 
Hospitalization in Routine Clinical Care: A First Analysis from the Empagliflozin 
Comparative Effectiveness and Safety (EMPRISE) Study."  Circulation. 2019 Apr 8. 
doi: 10.1161/CIRCULATIONAHA.118.039177
9
Estimated glomerular filtration rate (eGFR) (as per MDRD) < 30 mL/min/1.73m2 at
screening. The criterion is applicable after a target number of 220 subjects with eGFR < 30
mL/min are randomized
N/A
10
End stage liver disease, defined as the presence of acute or chronic liver disease and recent
history of one or more of the following: ascites, encephalopathy, variceal bleeding, bilirubin ≥
2.0 mg/dL, albumin level ≤ 3.5 g/dL, prothrombin time ≥ 4 seconds prolonged, international
normalized ratio (INR) ≥1.7 or prior liver transplant
Measured 180  days prior to drug initiation in any diagnosis position and inpatient or outpatient 
care setting
Liver disease- ICD-9 diagnosis:
070.xx, 570.xx- 573.xx 
456.0x-456.2x, 576.8x, 782.4x, 789.5x 
ICD-9 procedure codes:
39.1x, 42.91 
Patorno, Elisabetta et al. "Cardiovascular outcomes associated with canagliflozin 
versus other non-gliflozin antidiabetic drugs: population based cohort study." 
BMJ 2018;360:k119 http://dx.doi.org/10.1136/bmj.k119
Patorno, Elisabetta et al. "Empagliflozin and the Risk of Heart Failure 
Hospitalization in Routine Clinical Care: A First Analysis from the Empagliflozin 
Comparative Effectiveness and Safety (EMPRISE) Study."  Circulation. 2019 Apr 8. 
doi: 10.1161/CIRCULATIONAHA.118.039177
Appendix A

11
A prior solid organ transplant or awaiting solid organ transplant
Measured 180 days prior to drug initiation in any diagnosis/procedure position and inpatient or 
outpatient care setting
Please see Organ transplant sheet for ICD-9 Diagnosis codes  and ICD-9 and CPT procedure 
codes.
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
12
Malignant neoplasm requiring chemotherapy, surgery, radiation or palliative therapy in the previous 5 years. Subjects with intraepithelial 
squamous cell carcinoma of the skin (Bowen’s disease) treated with topical 5-fluorouracil (5FU) and subjects with basal cell skin cancer are 
allowed to enter the trial
Measured 1825 days prior to drug initiation in any procedure position and inpatient or 
outpatient care setting
History of malignant neoplasm in previous 5 years
 140.xx-208.xx (except 173.xx, non-melanoma skin cancer)
Patorno, Elisabetta et al. "Cardiovascular outcomes associated with canagliflozin 
versus other non-gliflozin antidiabetic drugs: population based cohort study." 
BMJ 2018;360:k119 http://dx.doi.org/10.1136/bmj.k119
Patorno, Elisabetta et al. "Empagliflozin and the Risk of Heart Failure 
Hospitalization in Routine Clinical Care: A First Analysis from the Empagliflozin 
Comparative Effectiveness and Safety (EMPRISE) Study."  Circulation. 2019 Apr 8. 
doi: 10.1161/CIRCULATIONAHA.118.039177
13
Family or personal history of multiple endocrine neoplasia type 2 (MEN2) or familial
medullary thyroid carcinoma (FMTC)
Measured 180  days prior to drug initiation in any diagnosis position and inpatient or outpatient 
care setting
ICD-9:
MEN Type I: 258.01
MEN Type IIA: 258.02
MEN Type IIB: 258.03
ICD-10: 
MEN, unspecified: E31.20
MEN, Type I: E31.21
MEN Type IIA: E31.22
MEN, Type IIB: E31.23
14
Personal history of non-familial medullary thyroid carcinoma
Measured 180  days prior to drug initiation in any diagnosis position and inpatient or outpatient 
care setting:
ICD9:
193 - MALIGNANT NEOPLASM OF THYROID GLAND
194.1 - MALIGNANT NEOPLASM OF PARATHYROID GLAND
ICD10: C73
(This is already covered in exclusion criteria #12, but measured and applied 
again)
15 Any acute condition or exacerbation of chronic condition that would in the Investigator's
opinion interfere with the initial trial visit schedule and procedures
N/A
16 Known or suspected hypersensitivity to trial product(s) or related products
N/A
17
Known use of non prescribed narcotics or illicit drugs
Measured 180  days prior to drug initiation in any diagnosis position and inpatient or outpatient 
care setting
Drug abuse or dependence
ICD-9: 292.xx, 304.xx, 305.2x-305.9x, 648.3x
Patorno, Elisabetta et al. "Cardiovascular outcomes associated with canagliflozin 
versus other non-gliflozin antidiabetic drugs: population based cohort study." 
BMJ 2018;360:k119 http://dx.doi.org/10.1136/bmj.k119
Patorno, Elisabetta et al. "Empagliflozin and the Risk of Heart Failure 
Hospitalization in Routine Clinical Care: A First Analysis from the Empagliflozin 
Comparative Effectiveness and Safety (EMPRISE) Study."  Circulation. 2019 Apr 8. 
doi: 10.1161/CIRCULATIONAHA.118.039177
18 Simultaneous participation in any other clinical trial of an investigational agent. Participation
in a clinical trial with investigational stent(s) is allowed
N/A
19 Previous participation in this trial. Participation is defined as randomized
N/A
20
Females of childbearing potential who are pregnant, breast-feeding or intend to become
pregnant or are not using adequate contraceptive methods (adequate contraceptive measures as
required by local law or practice)
Measured 180  days prior to drug initiation in any diagnosis position and inpatient or outpatient 
care setting or any drug dispensing prior to drug initiation:
i) Encounter for contraceptive management
V25
OR
Non-oral contraceptives (brand names)-
Depo-subQ
Provera 104
Depo-Provera, generic
Mirena
Ortho Evra
NuvaRing
Implanon
Oral contraceptives (generic names)-  See "oral contraceptives - generic" sheet.
Oral contraceptives (brand names)- See "oral contraceptives 
iii) plus pregnancy
Measured 180 days prior to drug initiation in any diagnosis position and inpatient or outpatient 
care setting- 
Refer to Pregnancy Sheet.
Krumme, Alexis A, et. al. “Study protocol for the dabigatran, apixaban, 
rivaroxaban, edoxaban, warfarin comparative effectiveness research study.” J. 
Comp. Eff. Res. (2018):7(1), 57–66. doi: 10.2217/cer-2017-0053.
We excluded patients using contraceptives because this trial includes non-
pregnant women, patients without childbearing potential, and patients who 
have childbearing potential but are taking precautions such as oral 
contraceptives (among many other ways) to avoid pregnancy during the trial 
period. It is impossible to implement such inclusion in real-world data, as 
childbearing potential is not recorded in claims. In this trials setting, this 
limitation to implement as an inclusion criteria is due to the following: i) lack of 
recording of contraceptives and other precautions to avoid pregnancy and ii) 
patients with diabetes and baseline CV tend to be older and are not likely to be at 
childbearing age. Therefore, we assumed that patients taking oral contraceptives 
have childbearing potential, so if they were to stop contraceptive use during 
follow-up, they could then become pregnant. Also, just to note, this exclusion of 
contraceptives use excludes very few patients (typically less than 0.1% of 
patients).
21 Receipt of any investigational medicinal product (IMP) within 30 days prior to this trial.
N/A
Appendix A

Trial ID 
Trial Name (with web links)
LEADER
Trial Name (with pdf links)
NCT
NCT01179048
Trial category
Secondary indication
Therapeutic Area
Endocrinology
RCT Category  
4a- Unintended S with label change
Brand Name
Generic Name
Liraglutide
Sponsor
Novo Nordisk A/S
Year
2016
Measurable endpoint
Composite of Cardiovascular Death, Non-fatal Myocardial Infarction, or Non-fatal Stroke
Exposure
Liraglutide
Comparator
Placebo
Population
Trial finding
HR = 0.87 (95% CI 0.78-0.97)
Notes
No. of Patients
Non-inferiority margin
HR = 1.30
Assay Sens. Endpoint
Assay Sens. Finding
Power
90% power to detect non-inferiority
Blinding
Statistical Method
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)
Appendix A

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

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

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

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 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

Organ Transplant
ICD-9 diagnoses:
V42.0 Kidney
V42.1 Heart
V42.6 Lung
V42.7 Liver
V42.8x Other specified organ or tissue
V42.81 Bone marrow 
V42.83 Pancreas 
V42.84 Intestines 
V42.89 Other
V42.9x Unspecified organ or tissue
V58.44 Aftercare following organ transplant
E878.0x Surgical operation with transplant of whole organ
996.8x Complications of transplanted organ
ICD-9 procedures:
33.5x Lung transplant
33.6x Combined heart-lung transplantation
37.51 Heart transplantation
41.0x Bone marrow 
46.97 Transplant of intestine
50.5x Liver transplant
52.8x Transplant of pancreas
55.6x Transplant of kidney
CPT4 codes
32851 LUNG TRANSPLANT, SINGLE; W/O CARDIOPULMONARY BYPASS
32852 LUNG TRANSPLANT, SINGLE; W/CARDIOPULMONARY BYPASS
32853 LUNG TRANSPLANT, DOUBLE (BILAT SEQUENTIAL/EN BLOC); W/O CARDIOPULMONARY BYPASS
32854 LUNG TRANSPLANT, DOUBLE (BILAT SEQUENTIAL/EN BLOC); W/CARDIOPULMONARY BYPASS
33935 HEART-LUNG TRANSPLANT W/RECIPIENT CARDIECTOMY-PNEUMONECTOMY
33945 HEART TRANSPLANT, W/WO RECIPIENT CARDIECTOMY
38240 BONE MARROW/BLOOD-DERIVED PERIPHERAL STEM CELL TRANSPLANTATION; ALLOGENIC
38241 BONE MARROW/BLOOD-DERIVED PERIPHERAL STEM CELL TRANSPLANTATION; AUTOLOGOUS
44135 INTESTINAL ALLOTRANSPLANTATION; FROM CADAVER DONOR
Appendix A

44136 INTESTINAL ALLOTRANSPLANTATION; FROM LIVING DONOR
47135 LIVER ALLOTRANSPLANTATION; ORTHOTOPIC, PARTIAL/WHOLE, FROM CADAVER/LIVING DONOR, 
ANY AGE
47136 LIVER ALLOTRANSPLANTATION; HETEROTOPIC, PARTIAL/WHOLE, FROM CADAVER/LIVING DONOR, 
ANY AGE
48554 TRANSPLANTATION, PANCREATIC ALLOGRAFT
48556 REMOVAL, TRANSPLANTED PANCREATIC ALLOGRAFT
50360 RENAL ALLOTRANSPLANTATION, IMPLANTATION, GRAFT; W/O DONOR & RECIPIENT NEPHRECTOMY
50365 RENAL ALLOTRANSPLANTATION, IMPLANTATION, GRAFT; W/RECIPIENT NEPHRECTOMY
50370 REMOVAL, TRANSPLANTED RENAL ALLOGRAFT
50380 RENAL AUTOTRANSPLANTATION, REIMPLANTATION, KIDNEY
Appendix A

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

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

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

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

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

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

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

oral contraceptive
norethindrone
norethindrone-mestranol
oral contraceptive
norgestrel
norgestrel
oral contraceptive
norgestrel
norgestrel-ethinyl estradiol
oral contraceptive
polyestradiol phosphate
polyestradiol phosphate
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

72.39   OTHER HIGH FORCEPS OPERATION
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

74.2   EXTRAPERITONEAL CESAREAN SECTION
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
Optum
MarketScan
Medicare
BEFORE PS MATCHING
The c-statistics for the propensity score model, pre-matching was 0.763. The post-matching c-statistic 
was 0.528.
The c-statistics for the propensity score model, pre-matching was 0.749. The post-matching 
c-statistic was 0.523.
The c-statistics for the propensity score model, pre-matching was 0.788. The post-matching c-statistic 
was 0.52.
Appendix B: Liraglutide vs DPP4i

Variable
Reference- DPP4i
Exposure- Liraglutide
St. Diff.
Reference- DPP4i
Exposure- Liraglutide
St. Diff.
Reference- DPP4i
Exposure- 
Liraglutide
St. Diff.
Reference- DPP4i
Exposure- Liraglutide
St. Diff.
Number of patients
                                       137,649                                           19,460 
143,337
                                      
21,041
                                         
454,700
                                    
44,778
                       
                                       735,686                                           85,279 
Age
...mean (sd)
70.07 (8.03)
66.00 (6.84)
0.55
66.74 (8.79)
63.07 (6.32)
0.48
74.48 (7.29)
70.59 (5.00)
0.62
72.15 (7.74)
67.69 (5.80)
0.65
...median [IQR]
69.00 [65.00, 76.00]
66.00 [61.00, 70.00]
0.40
64.00 [61.00, 72.00]
62.00 [60.00, 66.00]
0.26
73.00 [69.00, 79.00]9.00 [67.00, 73.00]
0.64
70.50 (7.74)
66.59 (5.80)
0.57
Age categories 
...18 - 54; n (%)
3,645 (2.6%)
1,088 (5.6%)
-0.15
7,490 (5.2%)
1,773 (8.4%)
-0.13
0 (0.0%)
0 (0.0%)
#DIV/0!
11,135 (1.5%)
2,861 (3.4%)
-0.12
...55 - 64; n (%)
30,092 (21.9%)
6,913 (35.5%)
-0.30
68,184 (47.6%)
12,865 (61.1%)
-0.27
7,142 (1.6%)
1,114 (2.5%)
-0.06
105,418 (14.3%)
20,892 (24.5%)
-0.26
...65 - 74; n (%)
64,422 (46.8%)
9,363 (48.1%)
-0.03
39,328 (27.4%)
5,193 (24.7%)
0.06
250,319 (55.1%)
34,945 (78.0%)
-0.50
354,069 (48.1%)
49,501 (58.0%)
-0.20
...>= 75; n (%)
39,490 (28.7%)
2,096 (10.8%)
0.46
28,335 (19.8%)
1,210 (5.8%)
0.43
197,239 (43.4%)
8,719 (19.5%)
0.53
265,064 (36.0%)
12,025 (14.1%)
0.52
Gender - United
...Males; n (%)
68,305 (49.6%)
9,191 (47.2%)
0.05
80,527 (56.2%)
10,789 (51.3%)
0.10
197,449 (43.4%)
19,778 (44.2%)
-0.02
346,281 (47.1%)
39,758 (46.6%)
0.01
...Females; n (%)
69,344 (50.4%)
10,269 (52.8%)
-0.05
62,810 (43.8%)
10,252 (48.7%)
-0.10
257,251 (56.6%)
25,000 (55.8%)
0.02
389,405 (52.9%)
45,521 (53.4%)
-0.01
Race 
...White; n (%)
N/A
N/A
N/A
N/A
337,843 (74.3%)
38,225 (85.4%)
-0.28
337,843 (74.3%)
38,225 (85.4%)
-0.28
...Black; n (%)
N/A
N/A
N/A
N/A
52,880 (11.6%)
3,806 (8.5%)
0.10
52,880 (11.6%)
3,806 (8.5%)
0.10
...Asian; n (%)
N/A
N/A
N/A
N/A
23,337 (5.1%)
531 (1.2%)
0.22
23,337 (5.1%)
531 (1.2%)
0.22
...Hispanic; n (%)
N/A
N/A
N/A
N/A
21,402 (4.7%)
801 (1.8%)
0.16
21,402 (4.7%)
801 (1.8%)
0.16
...North American Native; n (%)
N/A
N/A
N/A
N/A
2,392 (0.5%)
177 (0.4%)
0.01
2,392 (0.5%)
177 (0.4%)
0.01
...Other/Unknown; n (%)
N/A
N/A
N/A
N/A
16,846 (3.7%)
1,238 (2.8%)
0.05
16,846 (3.7%)
1,238 (2.8%)
0.05
Region - United  (lumping missing&other category with 
West)
...Northeast; n (%)
17,444 (12.7%)
1,756 (9.0%)
0.12
32,182 (22.5%)
3,998 (19.0%)
0.09
90,962 (20.0%)
7,000 (15.6%)
0.12
140,588 (19.1%)
12,754 (15.0%)
0.11
...South; n (%)
67,640 (49.1%)
10,375 (53.3%)
-0.08
34,576 (24.1%)
4,549 (21.6%)
0.06
193,181 (42.5%)
20,663 (46.1%)
-0.07
295,397 (40.2%)
35,587 (41.7%)
-0.03
...Midwest; n (%)
23,768 (17.3%)
3,839 (19.7%)
-0.06
59,121 (41.2%)
9,927 (47.2%)
-0.12
92,885 (20.4%)
10,345 (23.1%)
-0.07
175,774 (23.9%)
24,111 (28.3%)
-0.10
...West; n (%)
28,797 (20.9%)
3,490 (17.9%)
0.08
16,027 (11.2%)
2,339 (11.1%)
0.00
77,672 (17.1%)
6,770 (15.1%)
0.05
122,496 (16.7%)
12,599 (14.8%)
0.05
...Unknown+missing; n (%)
N/A
N/A
#VALUE!
1,431 (1.0%)
228 (1.1%)
-0.01
N/A
N/A
#VALUE!
1,431 (1.0%)
228 (1.1%)
-0.01
CV Covariates
Ischemic heart disease; n (%)
39,052 (28.4%)
5,847 (30.0%)
46,475 (32.4%)
6,900 (32.8%)
148,750 (32.7%)
13,938 (31.1%)
234,277 (31.8%)
26,685 (31.3%)
0.01
Acute MI; n (%)
2,315 (1.7%)
293 (1.5%)
2,658 (1.9%)
311 (1.5%)
8,356 (1.8%)
541 (1.2%)
13,329 (1.8%)
1,145 (1.3%)
0.04
ACS/unstable angina; n (%)
2,694 (2.0%)
397 (2.0%)
3,152 (2.2%)
438 (2.1%)
9,368 (2.1%)
748 (1.7%)
15,214 (2.1%)
1,583 (1.9%)
0.01
Old MI; n (%)
5,390 (3.9%)
786 (4.0%)
3,482 (2.4%)
438 (2.1%)
19,366 (4.3%)
1,616 (3.6%)
28,238 (3.8%)
2,840 (3.3%)
0.03
Stable angina; n (%)
5,780 (4.2%)
956 (4.9%)
4,996 (3.5%)
757 (3.6%)
18,469 (4.1%)
1,724 (3.9%)
29,245 (4.0%)
3,437 (4.0%)
0.00
Coronary atherosclerosis and other forms of chronic 
ischemic heart disease; n (%)
36,533 (26.5%)
5,496 (28.2%)
44,110 (30.8%)
6,595 (31.3%)
141,426 (31.1%)
13,340 (29.8%)
222,069 (30.2%)
25,431 (29.8%)
0.01
Other atherosclerosis with ICD10  ; n (%)
1,696 (1.2%)
203 (1.0%)
2,017 (1.4%)
241 (1.1%)
9,310 (2.0%)
763 (1.7%)
13,023 (1.8%)
1,207 (1.4%)
0.03
Previous cardiac procedure (CABG or PTCA or Stent) ; n (%)
1,201 (0.9%)
173 (0.9%)
1,786 (1.2%)
215 (1.0%)
3,709 (0.8%)
238 (0.5%)
6,696 (0.9%)
626 (0.7%)
0.02
History of CABG or PTCA; n (%)
9,173 (6.7%)
1,426 (7.3%)
5,910 (4.1%)
847 (4.0%)
40,580 (8.9%)
3,742 (8.4%)
55,663 (7.6%)
6,015 (7.1%)
0.02
Any stroke; n (%)
11,660 (8.5%)
1,418 (7.3%)
13,094 (9.1%)
1,523 (7.2%)
50,128 (11.0%)
3,815 (8.5%)
74,882 (10.2%)
6,756 (7.9%)
0.08
Ischemic stroke (w and w/o mention of cerebral 
infarction); n (%)
11,493 (8.3%)
1,407 (7.2%)
12,931 (9.0%)
1,502 (7.1%)
49,540 (10.9%)
3,782 (8.4%)
73,964 (10.1%)
6,691 (7.8%)
0.08
Hemorrhagic stroke; n (%)
380 (0.3%)
31 (0.2%)
374 (0.3%)
36 (0.2%)
1,464 (0.3%)
62 (0.1%)
2,218 (0.3%)
129 (0.2%)
0.02
TIA; n (%)
2,932 (2.1%)
331 (1.7%)
3,274 (2.3%)
368 (1.7%)
11,914 (2.6%)
775 (1.7%)
18,120 (2.5%)
1,474 (1.7%)
0.06
Other cerebrovascular disease; n (%)
3,355 (2.4%)
336 (1.7%)
2,664 (1.9%)
239 (1.1%)
15,532 (3.4%)
900 (2.0%)
21,551 (2.9%)
1,475 (1.7%)
0.08
Late effects of cerebrovascular disease; n (%)
3,094 (2.2%)
249 (1.3%)
2,107 (1.5%)
151 (0.7%)
13,901 (3.1%)
635 (1.4%)
19,102 (2.6%)
1,035 (1.2%)
0.10
Cerebrovascular procedure; n (%)
152 (0.1%)
21 (0.1%)
223 (0.2%)
24 (0.1%)
649 (0.1%)
45 (0.1%)
1,024 (0.1%)
90 (0.1%)
0.00
Heart failure (CHF); n (%)
15,587 (11.3%)
2,094 (10.8%)
13,361 (9.3%)
1,604 (7.6%)
66,067 (14.5%)
4,972 (11.1%)
95,015 (12.9%)
8,670 (10.2%)
0.08
Peripheral Vascular Disease (PVD) or PVD Surgery ; n (%)
13,999 (10.2%)
1,740 (8.9%)
12,644 (8.8%)
1,696 (8.1%)
61,829 (13.6%)
4,595 (10.3%)
88,472 (12.0%)
8,031 (9.4%)
0.08
Atrial fibrillation; n (%)
12,890 (9.4%)
1,576 (8.1%)
11,832 (8.3%)
1,252 (6.0%)
61,761 (13.6%)
4,822 (10.8%)
86,483 (11.8%)
7,650 (9.0%)
0.09
Other cardiac dysrhythmia; n (%)
15,067 (10.9%)
2,040 (10.5%)
12,311 (8.6%)
1,494 (7.1%)
65,098 (14.3%)
5,160 (11.5%)
92,476 (12.6%)
8,694 (10.2%)
0.08
Cardiac conduction disorders; n (%)
4,626 (3.4%)
552 (2.8%)
3,820 (2.7%)
436 (2.1%)
21,875 (4.8%)
1,645 (3.7%)
30,321 (4.1%)
2,633 (3.1%)
0.05
Other CVD; n (%)
18,872 (13.7%)
2,321 (11.9%)
18,649 (13.0%)
2,291 (10.9%)
80,263 (17.7%)
6,364 (14.2%)
117,784 (16.0%)
10,976 (12.9%)
0.09
Diabetes-related complications
Diabetic retinopathy; n (%)
9,042 (6.6%)
1,525 (7.8%)
6,336 (4.4%)
1,047 (5.0%)
31,125 (6.8%)
3,764 (8.4%)
46,503 (6.3%)
6,336 (7.4%)
-0.04
Diabetes with other ophthalmic manifestations; n (%)
1,130 (0.8%)
141 (0.7%)
4,518 (3.2%)
737 (3.5%)
12,856 (2.8%)
1,482 (3.3%)
18,504 (2.5%)
2,360 (2.8%)
-0.02
Retinal detachment, vitreous hemorrhage, vitrectomy; n 
(%)
545 (0.4%)
86 (0.4%)
493 (0.3%)
72 (0.3%)
1,742 (0.4%)
199 (0.4%)
2,780 (0.4%)
357 (0.4%)
0.00
Retinal laser coagulation therapy; n (%)
788 (0.6%)
123 (0.6%)
860 (0.6%)
140 (0.7%)
2,635 (0.6%)
299 (0.7%)
4,283 (0.6%)
562 (0.7%)
-0.01
Occurrence of Diabetic Neuropathy  ; n (%)
26,233 (19.1%)
4,774 (24.5%)
16,101 (11.2%)
3,065 (14.6%)
85,054 (18.7%)
10,489 (23.4%)
127,388 (17.3%)
18,328 (21.5%)
-0.11
Occurrence of diabetic nephropathy  with ICD10 ; n (%)
24,423 (17.7%)
3,525 (18.1%)
10,351 (7.2%)
1,700 (8.1%)
51,602 (11.3%)
5,673 (12.7%)
86,376 (11.7%)
10,898 (12.8%)
-0.03
Hypoglycemia ; n (%)
4,226 (3.1%)
479 (2.5%)
4,131 (2.9%)
640 (3.0%)
16,613 (3.7%)
1,391 (3.1%)
24,970 (3.4%)
2,510 (2.9%)
0.03
Hyperglycemia; n (%)
5,948 (4.3%)
763 (3.9%)
4,259 (3.0%)
551 (2.6%)
22,441 (4.9%)
1,684 (3.8%)
32,648 (4.4%)
2,998 (3.5%)
0.05
Disorders of fluid electrolyte and acid-base balance; n (%)
13,161 (9.6%)
1,370 (7.0%)
9,325 (6.5%)
966 (4.6%)
54,745 (12.0%)
3,370 (7.5%)
77,231 (10.5%)
5,706 (6.7%)
0.14
Diabetic ketoacidosis; n (%)
154 (0.1%)
21 (0.1%)
131 (0.1%)
23 (0.1%)
600 (0.1%)
53 (0.1%)
885 (0.1%)
97 (0.1%)
0.00
Hyperosmolar hyperglycemic nonketotic syndrome 
(HONK); n (%)
771 (0.6%)
97 (0.5%)
554 (0.4%)
74 (0.4%)
2,583 (0.6%)
198 (0.4%)
3,908 (0.5%)
369 (0.4%)
0.01
Diabetes with peripheral circulatory disorders with ICD-
10  ; n (%)
11,656 (8.5%)
1,552 (8.0%)
6,329 (4.4%)
895 (4.3%)
37,479 (8.2%)
3,252 (7.3%)
55,464 (7.5%)
5,699 (6.7%)
0.03
Diabetic Foot; n (%)
3,308 (2.4%)
511 (2.6%)
3,247 (2.3%)
499 (2.4%)
14,118 (3.1%)
1,392 (3.1%)
20,673 (2.8%)
2,402 (2.8%)
0.00
Gangrene ; n (%)
454 (0.3%)
52 (0.3%)
349 (0.2%)
34 (0.2%)
1,484 (0.3%)
86 (0.2%)
2,287 (0.3%)
172 (0.2%)
0.02
Unmatched
Optum
MarketScan
Medicare
POOLED
Table 1: Liraglutide vs DPP4i

Lower extremity amputation; n (%)
902 (0.7%)
151 (0.8%)
457 (0.3%)
72 (0.3%)
3,083 (0.7%)
234 (0.5%)
4,442 (0.6%)
457 (0.5%)
0.01
Osteomyelitis; n (%)
868 (0.6%)
113 (0.6%)
820 (0.6%)
123 (0.6%)
3,123 (0.7%)
230 (0.5%)
4,811 (0.7%)
466 (0.5%)
0.03
Skin infections ; n (%)
7,852 (5.7%)
1,189 (6.1%)
8,388 (5.9%)
1,314 (6.2%)
34,416 (7.6%)
3,405 (7.6%)
50,656 (6.9%)
5,908 (6.9%)
0.00
Erectile dysfunction; n (%)
3,529 (2.6%)
598 (3.1%)
3,240 (2.3%)
533 (2.5%)
9,341 (2.1%)
1,329 (3.0%)
16,110 (2.2%)
2,460 (2.9%)
-0.04
Diabetes with unspecified complication; n (%)
7,318 (5.3%)
1,250 (6.4%)
5,581 (3.9%)
1,021 (4.9%)
22,683 (5.0%)
2,517 (5.6%)
35,582 (4.8%)
4,788 (5.6%)
-0.04
Diabetes mellitus without mention of complications; n 
(%)
123,499 (89.7%)
16,933 (87.0%)
135,666 (94.6%)
19,693 (93.6%)
431,062 (94.8%)
41,725 (93.2%)
690,227 (93.8%)
78,351 (91.9%)
0.07
Hypertension: 1 inpatient or 2 outpatient claims within 
365 days; n (%)
131,194 (95.3%)
18,548 (95.3%)
126,524 (88.3%)
18,623 (88.5%)
440,639 (96.9%)
43,436 (97.0%)
698,357 (94.9%)
80,607 (94.5%)
0.02
Hyperlipidemia ; n (%)
107,176 (77.9%)
15,367 (79.0%)
96,564 (67.4%)
14,951 (71.1%)
366,495 (80.6%)
37,204 (83.1%)
570,235 (77.5%)
67,522 (79.2%)
-0.04
Edema; n (%)
11,564 (8.4%)
1,754 (9.0%)
8,574 (6.0%)
1,320 (6.3%)
51,918 (11.4%)
4,855 (10.8%)
72,056 (9.8%)
7,929 (9.3%)
0.02
Renal Dysfunction (non-diabetic) ; n (%)
38,064 (27.7%)
4,698 (24.1%)
25,130 (17.5%)
3,050 (14.5%)
122,954 (27.0%)
10,060 (22.5%)
186,148 (25.3%)
17,808 (20.9%)
0.10
Occurrence of acute renal disease ; n (%)
7,144 (5.2%)
626 (3.2%)
5,405 (3.8%)
390 (1.9%)
29,118 (6.4%)
1,432 (3.2%)
41,667 (5.7%)
2,448 (2.9%)
0.14
Occurrence of chronic renal insufficiency; n (%)
32,496 (23.6%)
4,049 (20.8%)
18,932 (13.2%)
2,380 (11.3%)
103,426 (22.7%)
8,660 (19.3%)
154,854 (21.0%)
15,089 (17.7%)
0.08
Chronic kidney disease ; n (%)
31,532 (22.9%)
3,938 (20.2%)
18,355 (12.8%)
2,295 (10.9%)
98,398 (21.6%)
8,194 (18.3%)
148,285 (20.2%)
14,427 (16.9%)
0.08
CKD Stage 3-4; n (%)
22,711 (16.5%)
2,899 (14.9%)
13,419 (9.4%)
1,727 (8.2%)
69,048 (15.2%)
5,916 (13.2%)
105,178 (14.3%)
10,542 (12.4%)
0.06
Occurrence of hypertensive nephropathy; n (%)
14,200 (10.3%)
1,746 (9.0%)
7,062 (4.9%)
877 (4.2%)
48,654 (10.7%)
3,522 (7.9%)
69,916 (9.5%)
6,145 (7.2%)
0.08
Occurrence of miscellaneous renal insufficiency ; n (%)
9,326 (6.8%)
1,025 (5.3%)
7,297 (5.1%)
794 (3.8%)
39,407 (8.7%)
2,911 (6.5%)
56,030 (7.6%)
4,730 (5.5%)
0.08
Glaucoma or cataracts ; n (%)
31,519 (22.9%)
4,099 (21.1%)
27,054 (18.9%)
3,736 (17.8%)
125,334 (27.6%)
12,591 (28.1%)
183,907 (25.0%)
20,426 (24.0%)
0.02
Cellulitis or abscess of toe; n (%)
1,938 (1.4%)
309 (1.6%)
1,442 (1.0%)
215 (1.0%)
7,035 (1.5%)
672 (1.5%)
10,415 (1.4%)
1,196 (1.4%)
0.00
Foot ulcer; n (%)
3,246 (2.4%)
492 (2.5%)
3,305 (2.3%)
501 (2.4%)
14,168 (3.1%)
1,370 (3.1%)
20,719 (2.8%)
2,363 (2.8%)
0.00
Bladder stones; n (%)
206 (0.1%)
14 (0.1%)
179 (0.1%)
22 (0.1%)
782 (0.2%)
73 (0.2%)
1,167 (0.2%)
109 (0.1%)
0.03
Kidney stones; n (%)
3,106 (2.3%)
470 (2.4%)
3,373 (2.4%)
521 (2.5%)
12,208 (2.7%)
1,306 (2.9%)
18,687 (2.5%)
2,297 (2.7%)
-0.01
Urinary tract infections (UTIs); n (%)
14,737 (10.7%)
1,747 (9.0%)
10,494 (7.3%)
1,378 (6.5%)
72,585 (16.0%)
5,522 (12.3%)
97,816 (13.3%)
8,647 (10.1%)
0.10
Dipstick urinalysis; n (%)
53,139 (38.6%)
7,035 (36.2%)
46,136 (32.2%)
6,828 (32.5%)
195,617 (43.0%)
17,919 (40.0%)
294,892 (40.1%)
31,782 (37.3%)
0.06
Non-dipstick urinalysis; n (%)
59,310 (43.1%)
8,756 (45.0%)
43,231 (30.2%)
7,574 (36.0%)
186,851 (41.1%)
20,869 (46.6%)
289,392 (39.3%)
37,199 (43.6%)
-0.09
Urine function test; n (%)
3,515 (2.6%)
470 (2.4%)
3,953 (2.8%)
508 (2.4%)
15,791 (3.5%)
1,537 (3.4%)
23,259 (3.2%)
2,515 (2.9%)
0.02
Cytology; n (%)
1,262 (0.9%)
129 (0.7%)
1,590 (1.1%)
181 (0.9%)
5,167 (1.1%)
408 (0.9%)
8,019 (1.1%)
718 (0.8%)
0.03
Cystos; n (%)
1,614 (1.2%)
241 (1.2%)
1,968 (1.4%)
261 (1.2%)
6,557 (1.4%)
662 (1.5%)
10,139 (1.4%)
1,164 (1.4%)
0.00
Other Covariates
Liver disease; n (%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
#VALUE!
000 (0.0%)
#VALUE!
Osteoarthritis; n (%)
24,718 (18.0%)
3,864 (19.9%)
19,572 (13.7%)
3,249 (15.4%)
113,591 (25.0%)
11,128 (24.9%)
157,881 (21.5%)
18,241 (21.4%)
0.00
Other arthritis, arthropathies and musculoskeletal pain; n 
(%)
51,843 (37.7%)
7,843 (40.3%)
48,371 (33.7%)
7,762 (36.9%)
213,921 (47.0%)
21,204 (47.4%)
314,135 (42.7%)
36,809 (43.2%)
-0.01
Dorsopathies; n (%)
29,810 (21.7%)
5,119 (26.3%)
26,948 (18.8%)
4,549 (21.6%)
122,994 (27.0%)
13,499 (30.1%)
179,752 (24.4%)
23,167 (27.2%)
-0.06
Fractures; n (%)
4,494 (3.3%)
551 (2.8%)
4,287 (3.0%)
536 (2.5%)
20,423 (4.5%)
1,579 (3.5%)
29,204 (4.0%)
2,666 (3.1%)
0.05
Falls ; n (%)
5,598 (4.1%)
619 (3.2%)
1,915 (1.3%)
186 (0.9%)
24,100 (5.3%)
1,497 (3.3%)
31,613 (4.3%)
2,302 (2.7%)
0.09
Osteoporosis; n (%)
8,985 (6.5%)
791 (4.1%)
5,336 (3.7%)
613 (2.9%)
45,290 (10.0%)
2,896 (6.5%)
59,611 (8.1%)
4,300 (5.0%)
0.13
Hyperthyroidism; n (%)
1,099 (0.8%)
129 (0.7%)
819 (0.6%)
109 (0.5%)
4,909 (1.1%)
417 (0.9%)
6,827 (0.9%)
655 (0.8%)
0.01
Hypothyroidism ; n (%)
22,924 (16.7%)
3,807 (19.6%)
16,633 (11.6%)
3,024 (14.4%)
73,337 (16.1%)
7,801 (17.4%)
112,894 (15.3%)
14,632 (17.2%)
-0.05
Other disorders of thyroid gland ; n (%)
5,049 (3.7%)
994 (5.1%)
4,703 (3.3%)
1,015 (4.8%)
20,113 (4.4%)
2,618 (5.8%)
29,865 (4.1%)
4,627 (5.4%)
-0.06
Depression; n (%)
11,373 (8.3%)
2,024 (10.4%)
8,745 (6.1%)
1,648 (7.8%)
52,459 (11.5%)
5,355 (12.0%)
72,577 (9.9%)
9,027 (10.6%)
-0.02
Anxiety; n (%)
9,539 (6.9%)
1,739 (8.9%)
6,316 (4.4%)
1,089 (5.2%)
40,669 (8.9%)
3,761 (8.4%)
56,524 (7.7%)
6,589 (7.7%)
0.00
Sleep_Disorder; n (%)
9,838 (7.1%)
2,106 (10.8%)
14,014 (9.8%)
3,538 (16.8%)
39,861 (8.8%)
5,970 (13.3%)
63,713 (8.7%)
11,614 (13.6%)
-0.16
Dementia; n (%)
7,136 (5.2%)
406 (2.1%)
4,259 (3.0%)
213 (1.0%)
43,046 (9.5%)
1,485 (3.3%)
54,441 (7.4%)
2,104 (2.5%)
0.23
Delirium; n (%)
2,267 (1.6%)
146 (0.8%)
1,699 (1.2%)
93 (0.4%)
13,093 (2.9%)
487 (1.1%)
17,059 (2.3%)
726 (0.9%)
0.11
Psychosis; n (%)
1,770 (1.3%)
132 (0.7%)
1,328 (0.9%)
80 (0.4%)
12,498 (2.7%)
410 (0.9%)
15,596 (2.1%)
622 (0.7%)
0.12
Obesity; n (%)
24,341 (17.7%)
6,527 (33.5%)
16,530 (11.5%)
4,589 (21.8%)
63,591 (14.0%)
11,795 (26.3%)
104,462 (14.2%)
22,911 (26.9%)
-0.32
Overweight; n (%)
7,251 (5.3%)
839 (4.3%)
2,562 (1.8%)
362 (1.7%)
15,407 (3.4%)
1,228 (2.7%)
25,220 (3.4%)
2,429 (2.8%)
0.03
Smoking; n (%)
14,135 (10.3%)
2,261 (11.6%)
7,307 (5.1%)
980 (4.7%)
55,934 (12.3%)
5,420 (12.1%)
77,376 (10.5%)
8,661 (10.2%)
0.01
Alcohol abuse or dependence; n (%)
870 (0.6%)
86 (0.4%)
555 (0.4%)
59 (0.3%)
2,506 (0.6%)
159 (0.4%)
3,931 (0.5%)
304 (0.4%)
0.01
Drug abuse or dependence; n (%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
#VALUE!
00 (0.0%)
#VALUE!
COPD; n (%)
14,198 (10.3%)
1,973 (10.1%)
10,318 (7.2%)
1,275 (6.1%)
56,882 (12.5%)
4,948 (11.1%)
81,398 (11.1%)
8,196 (9.6%)
0.05
Asthma; n (%)
7,979 (5.8%)
1,423 (7.3%)
6,641 (4.6%)
1,245 (5.9%)
30,514 (6.7%)
3,532 (7.9%)
45,134 (6.1%)
6,200 (7.3%)
-0.05
Obstructive sleep apnea; n (%)
11,663 (8.5%)
3,609 (18.5%)
13,366 (9.3%)
3,712 (17.6%)
29,991 (6.6%)
6,268 (14.0%)
55,020 (7.5%)
13,589 (15.9%)
-0.26
Pneumonia; n (%)
4,591 (3.3%)
441 (2.3%)
4,180 (2.9%)
411 (2.0%)
20,756 (4.6%)
1,181 (2.6%)
29,527 (4.0%)
2,033 (2.4%)
0.09
Imaging; n (%)
241 (0.2%)
26 (0.1%)
159 (0.1%)
15 (0.1%)
1,166 (0.3%)
50 (0.1%)
1,566 (0.2%)
91 (0.1%)
0.03
Diabetes Medications
DM Medications - AGIs; n (%)
786 (0.6%)
99 (0.5%)
633 (0.4%)
81 (0.4%)
2,985 (0.7%)
256 (0.6%)
4,404 (0.6%)
436 (0.5%)
0.01
DM Medications - Glitazones; n (%)
16,871 (12.3%)
2,269 (11.7%)
22,209 (15.5%)
3,302 (15.7%)
45,631 (10.0%)
4,744 (10.6%)
84,711 (11.5%)
10,315 (12.1%)
-0.02
DM Medications - Insulin; n (%)
8,831 (6.4%)
3,535 (18.2%)
8,235 (5.7%)
3,628 (17.2%)
34,893 (7.7%)
8,976 (20.0%)
51,959 (7.1%)
16,139 (18.9%)
-0.36
DM Medications - Meglitinides; n (%)
1,810 (1.3%)
216 (1.1%)
2,892 (2.0%)
362 (1.7%)
9,363 (2.1%)
694 (1.5%)
14,065 (1.9%)
1,272 (1.5%)
0.03
DM Medications - Metformin; n (%)
96,324 (70.0%)
12,338 (63.4%)
102,745 (71.7%)
13,977 (66.4%)
309,951 (68.2%)
29,057 (64.9%)
509,020 (69.2%)
55,372 (64.9%)
0.09
Concomitant initiation or current use of SGLT2i; n (%)
3,835 (2.8%)
1,082 (5.6%)
3,828 (2.7%)
1,012 (4.8%)
7,655 (1.7%)
1,707 (3.8%)
15,318 (2.1%)
3,801 (4.5%)
-0.13
Concomitant initiation or current use of AGIs; n (%)
545 (0.4%)
67 (0.3%)
447 (0.3%)
48 (0.2%)
2,115 (0.5%)
174 (0.4%)
3,107 (0.4%)
289 (0.3%)
0.02
Concomitant initiation or current use of Glitazones; n (%)
10,920 (7.9%)
1,656 (8.5%)
14,399 (10.0%)
2,407 (11.4%)
30,752 (6.8%)
3,542 (7.9%)
56,071 (7.6%)
7,605 (8.9%)
-0.05
Concomitant initiation or current use of 2nd Generation 
SUs; n (%)
51,739 (37.6%)
5,743 (29.5%)
49,362 (34.4%)
6,207 (29.5%)
174,253 (38.3%)
14,795 (33.0%)
275,354 (37.4%)
26,745 (31.4%)
0.13
Concomitant initiation or current use of Insulin; n (%)
4,972 (3.6%)
2,133 (11.0%)
4,622 (3.2%)
2,182 (10.4%)
19,944 (4.4%)
5,427 (12.1%)
29,538 (4.0%)
9,742 (11.4%)
-0.28
Concomitant initiation or current use of Meglitinides; n 
(%)
1,297 (0.9%)
137 (0.7%)
2,114 (1.5%)
252 (1.2%)
6,897 (1.5%)
472 (1.1%)
10,308 (1.4%)
861 (1.0%)
0.04
Concomitant initiation or current use of Metformin; n (%)
81,351 (59.1%)
10,014 (51.5%)
87,805 (61.3%)
11,257 (53.5%)
260,323 (57.3%)
23,718 (53.0%)
429,479 (58.4%)
44,989 (52.8%)
0.11
Past use of SGLT2i  ; n (%)
1,518 (1.1%)
416 (2.1%)
1,114 (0.8%)
357 (1.7%)
3,164 (0.7%)
758 (1.7%)
5,796 (0.8%)
1,531 (1.8%)
-0.09
Past use of AGIs ; n (%)
241 (0.2%)
32 (0.2%)
186 (0.1%)
33 (0.2%)
870 (0.2%)
82 (0.2%)
1,297 (0.2%)
147 (0.2%)
0.00
Past use of Glitazones  ; n (%)
5,951 (4.3%)
613 (3.2%)
7,810 (5.4%)
895 (4.3%)
14,879 (3.3%)
1,202 (2.7%)
28,640 (3.9%)
2,710 (3.2%)
0.04
Table 1: Liraglutide vs DPP4i

Past use of 2nd Generation SUs; n (%)
11,899 (8.6%)
1,526 (7.8%)
11,721 (8.2%)
1,708 (8.1%)
39,000 (8.6%)
3,849 (8.6%)
62,620 (8.5%)
7,083 (8.3%)
0.01
Past use of Insulin  ; n (%)
3,859 (2.8%)
1,402 (7.2%)
3,613 (2.5%)
1,446 (6.9%)
14,951 (3.3%)
3,549 (7.9%)
22,423 (3.0%)
6,397 (7.5%)
-0.20
Past use of Meglitinides  ; n (%)
513 (0.4%)
79 (0.4%)
778 (0.5%)
110 (0.5%)
2,466 (0.5%)
222 (0.5%)
3,757 (0.5%)
411 (0.5%)
0.00
Past use of metformin (final)  ; n (%)
14,973 (10.9%)
2,324 (11.9%)
14,940 (10.4%)
2,720 (12.9%)
49,628 (10.9%)
5,339 (11.9%)
79,541 (10.8%)
10,383 (12.2%)
-0.04
Other Medications
Use of ACE inhibitors; n (%)
64,855 (47.1%)
8,724 (44.8%)
66,162 (46.2%)
9,336 (44.4%)
205,264 (45.1%)
19,889 (44.4%)
336,281 (45.7%)
37,949 (44.5%)
0.02
Use of ARBs; n (%)
43,355 (31.5%)
6,562 (33.7%)
47,088 (32.9%)
7,639 (36.3%)
151,976 (33.4%)
15,859 (35.4%)
242,419 (33.0%)
30,060 (35.2%)
-0.05
Use of Loop Diuretics - United; n (%)
22,407 (16.3%)
3,599 (18.5%)
22,391 (15.6%)
3,594 (17.1%)
98,566 (21.7%)
9,891 (22.1%)
143,364 (19.5%)
17,084 (20.0%)
-0.01
Use of other diuretics- United; n (%)
4,749 (3.5%)
912 (4.7%)
5,277 (3.7%)
970 (4.6%)
18,328 (4.0%)
2,185 (4.9%)
28,354 (3.9%)
4,067 (4.8%)
-0.04
Use of nitrates-United; n (%)
9,362 (6.8%)
1,414 (7.3%)
11,234 (7.8%)
1,585 (7.5%)
40,868 (9.0%)
3,563 (8.0%)
61,464 (8.4%)
6,562 (7.7%)
0.03
Use of other hypertension drugs; n (%)
12,044 (8.7%)
1,520 (7.8%)
11,547 (8.1%)
1,498 (7.1%)
44,046 (9.7%)
3,845 (8.6%)
67,637 (9.2%)
6,863 (8.0%)
0.04
Use of digoxin- United; n (%)
3,440 (2.5%)
325 (1.7%)
4,412 (3.1%)
397 (1.9%)
17,606 (3.9%)
1,026 (2.3%)
25,458 (3.5%)
1,748 (2.0%)
0.09
Use of Anti-arrhythmics; n (%)
2,573 (1.9%)
343 (1.8%)
3,016 (2.1%)
359 (1.7%)
11,844 (2.6%)
978 (2.2%)
17,433 (2.4%)
1,680 (2.0%)
0.03
Use of COPD/asthma meds- United; n (%)
21,727 (15.8%)
3,388 (17.4%)
22,229 (15.5%)
3,787 (18.0%)
83,884 (18.4%)
8,641 (19.3%)
127,840 (17.4%)
15,816 (18.5%)
-0.03
Use of statins; n (%)
98,588 (71.6%)
14,035 (72.1%)
100,854 (70.4%)
15,110 (71.8%)
328,079 (72.2%)
32,658 (72.9%)
527,521 (71.7%)
61,803 (72.5%)
-0.02
Use of other lipid-lowering drugs; n (%)
17,895 (13.0%)
2,774 (14.3%)
23,475 (16.4%)
3,929 (18.7%)
60,974 (13.4%)
6,846 (15.3%)
102,344 (13.9%)
13,549 (15.9%)
-0.06
Use of antiplatelet agents; n (%)
20,986 (15.2%)
3,009 (15.5%)
27,448 (19.1%)
4,060 (19.3%)
79,242 (17.4%)
7,048 (15.7%)
127,676 (17.4%)
14,117 (16.6%)
0.02
Use of oral anticoagulants (Dabigatran, Rivaroxaban, 
Apixaban, Warfarin); n (%)
10,989 (8.0%)
1,483 (7.6%)
11,524 (8.0%)
1,393 (6.6%)
49,547 (10.9%)
4,301 (9.6%)
72,060 (9.8%)
7,177 (8.4%)
0.05
Use of heparin and other low-molecular weight heparins; 
n (%)
670 (0.5%)
109 (0.6%)
47 (0.0%)
1 (0.0%)
2,464 (0.5%)
208 (0.5%)
3,181 (0.4%)
318 (0.4%)
0.00
Use of NSAIDs; n (%)
21,041 (15.3%)
3,463 (17.8%)
21,453 (15.0%)
3,650 (17.3%)
78,824 (17.3%)
8,045 (18.0%)
121,318 (16.5%)
15,158 (17.8%)
-0.03
Use of oral corticosteroids; n (%)
21,735 (15.8%)
3,298 (16.9%)
22,026 (15.4%)
3,318 (15.8%)
83,442 (18.4%)
8,085 (18.1%)
127,203 (17.3%)
14,701 (17.2%)
0.00
Use of bisphosphonate (United); n (%)
4,679 (3.4%)
350 (1.8%)
3,102 (2.2%)
310 (1.5%)
20,383 (4.5%)
1,052 (2.3%)
28,164 (3.8%)
1,712 (2.0%)
0.11
Use of opioids- United; n (%)
32,642 (23.7%)
5,647 (29.0%)
35,653 (24.9%)
6,129 (29.1%)
117,214 (25.8%)
13,198 (29.5%)
185,509 (25.2%)
24,974 (29.3%)
-0.09
Use of antidepressants; n (%)
30,300 (22.0%)
6,060 (31.1%)
29,496 (20.6%)
6,202 (29.5%)
116,636 (25.7%)
14,399 (32.2%)
176,432 (24.0%)
26,661 (31.3%)
-0.16
Use of antipsychotics; n (%)
3,211 (2.3%)
453 (2.3%)
2,529 (1.8%)
370 (1.8%)
17,910 (3.9%)
1,052 (2.3%)
23,650 (3.2%)
1,875 (2.2%)
0.06
Use of anticonvulsants; n (%)
20,811 (15.1%)
4,095 (21.0%)
16,587 (11.6%)
3,194 (15.2%)
78,878 (17.3%)
8,935 (20.0%)
116,276 (15.8%)
16,224 (19.0%)
-0.08
Use of lithium- United; n (%)
152 (0.1%)
22 (0.1%)
153 (0.1%)
27 (0.1%)
574 (0.1%)
55 (0.1%)
879 (0.1%)
104 (0.1%)
0.00
Use of Benzos- United; n (%)
11,760 (8.5%)
2,281 (11.7%)
14,941 (10.4%)
2,594 (12.3%)
45,770 (10.1%)
4,990 (11.1%)
72,471 (9.9%)
9,865 (11.6%)
-0.05
Use of anxiolytics/hypnotics- United; n (%)
7,916 (5.8%)
1,425 (7.3%)
9,470 (6.6%)
1,735 (8.2%)
31,510 (6.9%)
3,415 (7.6%)
48,896 (6.6%)
6,575 (7.7%)
-0.04
Use of dementia meds- United; n (%)
4,155 (3.0%)
205 (1.1%)
3,015 (2.1%)
147 (0.7%)
27,566 (6.1%)
918 (2.1%)
34,736 (4.7%)
1,270 (1.5%)
0.19
Use of antiparkinsonian meds- United; n (%)
3,405 (2.5%)
689 (3.5%)
3,131 (2.2%)
651 (3.1%)
15,911 (3.5%)
1,828 (4.1%)
22,447 (3.1%)
3,168 (3.7%)
-0.03
Any use of pramlintide; n (%)
5 (0.0%)
5 (0.0%)
17 (0.0%)
30 (0.1%)
18 (0.0%)
19 (0.0%)
040 (0.0%)
054 (0.1%)
-0.04
Any use of 1st generation sulfonylureas; n (%)
26 (0.0%)
0 (0.0%)
35 (0.0%)
1 (0.0%)
**
**
**
**
**
Entresto (sacubitril/valsartan); n (%)
216 (0.2%)
49 (0.3%)
65 (0.0%)
13 (0.1%)
267 (0.1%)
27 (0.1%)
548 (0.1%)
089 (0.1%)
0.00
Initiation as monotherapy  ; n (%)
15,454 (11.2%)
0 (0.0%)
15,217 (10.6%)
0 (0.0%)
42,437 (9.3%)
0 (0.0%)
73,108 (9.9%)
#VALUE!
#VALUE!
Labs
                                       280,986                                           40,501 
Lab values- HbA1c (%) ; n (%)
50,437 (36.6%)
7,316 (37.6%)
8,493 (5.9%)
1,188 (5.6%)
N/A
N/A
58,930 (21.0%)
8,504 (21.0%)
0.00
Lab values- HbA1c (%) (within 3 months) ; n (%)
39,878 (29.0%)
5,615 (28.9%)
6,736 (4.7%)
933 (4.4%)
N/A
N/A
46,614 (16.6%)
6,548 (16.2%)
0.01
Lab values- HbA1c (%) (within 6 months) ; n (%)
50,437 (36.6%)
7,316 (37.6%)
8,493 (5.9%)
1,188 (5.6%)
N/A
N/A
58,930 (21.0%)
8,504 (21.0%)
0.00
Lab values- BNP; n (%)
1,367 (1.0%)
208 (1.1%)
207 (0.1%)
35 (0.2%)
N/A
N/A
1,574 (0.6%)
243 (0.6%)
0.00
Lab values- BNP (within 3 months); n (%)
859 (0.6%)
122 (0.6%)
133 (0.1%)
28 (0.1%)
N/A
N/A
992 (0.4%)
150 (0.4%)
0.00
Lab values- BNP (within 6 months); n (%)
1,367 (1.0%)
208 (1.1%)
207 (0.1%)
35 (0.2%)
N/A
N/A
1,574 (0.6%)
243 (0.6%)
0.00
Lab values- BUN (mg/dl); n (%)
51,823 (37.6%)
7,494 (38.5%)
8,517 (5.9%)
1,204 (5.7%)
N/A
N/A
60,340 (21.5%)
8,698 (21.5%)
0.00
Lab values- BUN (mg/dl) (within 3 months); n (%)
40,495 (29.4%)
5,663 (29.1%)
6,596 (4.6%)
918 (4.4%)
N/A
N/A
47,091 (16.8%)
6,581 (16.2%)
0.02
Lab values- BUN (mg/dl) (within 6 months); n (%)
51,823 (37.6%)
7,494 (38.5%)
8,517 (5.9%)
1,204 (5.7%)
N/A
N/A
60,340 (21.5%)
8,698 (21.5%)
0.00
Lab values- Creatinine (mg/dl) ; n (%)
53,070 (38.6%)
7,701 (39.6%)
8,888 (6.2%)
1,253 (6.0%)
N/A
N/A
61,958 (22.1%)
8,954 (22.1%)
0.00
Lab values- Creatinine (mg/dl) (within 3 months) ; n (%)
41,526 (30.2%)
5,821 (29.9%)
6,892 (4.8%)
950 (4.5%)
N/A
N/A
48,418 (17.2%)
6,771 (16.7%)
0.01
Lab values- Creatinine (mg/dl) (within 6 months) ; n (%)
53,070 (38.6%)
7,701 (39.6%)
8,888 (6.2%)
1,253 (6.0%)
N/A
N/A
61,958 (22.1%)
8,954 (22.1%)
0.00
Lab values- HDL level (mg/dl); n (%)
43,367 (31.5%)
6,185 (31.8%)
7,438 (5.2%)
1,046 (5.0%)
N/A
N/A
50,805 (18.1%)
7,231 (17.9%)
0.01
Lab values- HDL level (mg/dl) (within 3 months); n (%)
31,824 (23.1%)
4,395 (22.6%)
5,475 (3.8%)
765 (3.6%)
N/A
N/A
37,299 (13.3%)
5,160 (12.7%)
0.02
Lab values- HDL level (mg/dl) (within 6 months); n (%)
43,367 (31.5%)
6,185 (31.8%)
7,438 (5.2%)
1,046 (5.0%)
N/A
N/A
50,805 (18.1%)
7,231 (17.9%)
0.01
Lab values- LDL level (mg/dl) ; n (%)
44,416 (32.3%)
6,396 (32.9%)
7,816 (5.5%)
1,106 (5.3%)
N/A
N/A
52,232 (18.6%)
7,502 (18.5%)
0.00
Lab values- LDL level (mg/dl) (within 3 months) ; n (%)
32,596 (23.7%)
4,554 (23.4%)
5,755 (4.0%)
803 (3.8%)
N/A
N/A
38,351 (13.6%)
5,357 (13.2%)
0.01
Lab values- LDL level (mg/dl) (within 6 months) ; n (%)
44,416 (32.3%)
6,396 (32.9%)
7,816 (5.5%)
1,106 (5.3%)
N/A
N/A
52,232 (18.6%)
7,502 (18.5%)
0.00
Lab values- NT-proBNP; n (%)
203 (0.1%)
36 (0.2%)
20 (0.0%)
3 (0.0%)
N/A
N/A
223 (0.1%)
39 (0.1%)
0.00
Lab values- NT-proBNP (within 3 months); n (%)
125 (0.1%)
23 (0.1%)
14 (0.0%)
1 (0.0%)
N/A
N/A
139 (0.0%)
24 (0.1%)
-
Lab values- NT-proBNP (within 6 months); n (%)
203 (0.1%)
36 (0.2%)
20 (0.0%)
3 (0.0%)
N/A
N/A
223 (0.1%)
39 (0.1%)
-
Lab values- Total cholesterol (mg/dl) ; n (%)
43,827 (31.8%)
6,311 (32.4%)
7,593 (5.3%)
1,060 (5.0%)
N/A
N/A
51,420 (18.3%)
7,371 (18.2%)
0.00
Lab values- Total cholesterol (mg/dl) (within 3 months) ; n 
(%)
32,199 (23.4%)
4,492 (23.1%)
5,597 (3.9%)
775 (3.7%)
N/A
N/A
37,796 (13.5%)
5,267 (13.0%)
0.01
Lab values- Total cholesterol (mg/dl) (within 6 months) ; n 
(%)
43,827 (31.8%)
6,311 (32.4%)
7,593 (5.3%)
1,060 (5.0%)
N/A
N/A
51,420 (18.3%)
7,371 (18.2%)
0.00
Lab values- Triglyceride level (mg/dl); n (%)
43,538 (31.6%)
6,253 (32.1%)
7,502 (5.2%)
1,041 (4.9%)
N/A
N/A
51,040 (18.2%)
7,294 (18.0%)
0.01
Lab values- Triglyceride level (mg/dl) (within 3 months); n 
(%)
31,997 (23.2%)
4,455 (22.9%)
5,533 (3.9%)
761 (3.6%)
N/A
N/A
37,530 (13.4%)
5,216 (12.9%)
0.01
Lab values- Triglyceride level (mg/dl) (within 6 months); n 
(%)
43,538 (31.6%)
6,253 (32.1%)
7,502 (5.2%)
1,041 (4.9%)
N/A
N/A
51,040 (18.2%)
7,294 (18.0%)
0.01
Lab result number- HbA1c (%) mean (only 2 to 20 
included) 
50,233
                                         
7,279
                                            
8,105
                                            
1,124
                                            
N/A
N/A
                                          58,338                                              8,403 
...mean (sd)
7.95 (1.60)
8.04 (1.73)
-0.05
7.97 (1.62)
8.03 (1.73)
-0.04
N/A
N/A
#VALUE!
7.95 (1.60)
8.04 (1.73)
-0.05
...median [IQR]
7.60 [6.90, 8.65]
7.70 [6.80, 8.95]
-0.06
7.60 [6.90, 8.70]
7.75 [6.80, 8.95]
-0.09
N/A
N/A
#VALUE!
7.60 (1.60)
7.71 (1.73)
-0.07
...Missing; n (%)
87,416 (63.5%)
12,181 (62.6%)
0.02
135,232 (94.3%)
19,917 (94.7%)
-0.02
N/A
N/A
#VALUE!
222,648 (79.2%)
32,098 (79.3%)
0.00
Table 1: Liraglutide vs DPP4i

Lab result number- BNP mean 
1,367
                                            
208
                                                
207
                                                
35
                                                   
N/A
N/A
                                             1,574                                                  243 
...mean (sd)
202.08 (359.17)
111.51 (209.59)
0.31
1,686.84 (19,478.97)
103.76 (169.94)
0.11
N/A
N/A
#VALUE!
397.34 (7061.56)
110.39 (204.89)
0.06
...median [IQR]
88.65 [33.40, 217.10]
43.85 [20.85, 111.38]
0.15
93.00 [34.00, 253.00]
45.70 [17.00, 124.00]
0.00
N/A
N/A
#VALUE!
#VALUE!
#VALUE!
#VALUE!
...Missing; n (%)
136,282 (99.0%)
19,252 (98.9%)
0.01
143,130 (99.9%)
21,006 (99.8%)
0.03
N/A
N/A
#VALUE!
279,412 (99.4%)
40,258 (99.4%)
0.00
Lab result number- BUN (mg/dl) mean 
                                          51,823                                              7,494 
                                             8,517                                              1,204 
N/A
N/A
                                          60,340                                              8,698 
...mean (sd)
19.96 (8.65)
19.56 (8.25)
0.05
296.19 (6,635.25)
675.16 (11,808.66)
-0.04
N/A
N/A
#VALUE!
58.95 (2492.79)
110.31 (4392.37)
-0.01
...median [IQR]
18.00 [14.00, 23.00]
18.00 [14.00, 23.00]
0.00
17.50 [14.00, 22.00]
18.00 [14.31, 22.00]
0.00
N/A
N/A
#VALUE!
#VALUE!
#VALUE!
#VALUE!
...Missing; n (%)
85,826 (62.4%)
11,966 (61.5%)
0.02
134,820 (94.1%)
19,837 (94.3%)
-0.01
N/A
N/A
#VALUE!
220,646 (78.5%)
31,803 (78.5%)
0.00
Lab result number- Creatinine (mg/dl) mean (only 0.1 to 
15 included) 
                                          52,715                                              7,656 
                                             8,281                                              1,142 
N/A
N/A
                                          60,996                                              8,798 
...mean (sd)
1.08 (0.42)
1.04 (0.37)
0.10
1.06 (0.41)
1.01 (0.32)
0.14
N/A
N/A
#VALUE!
1.08 (0.42)
1.04 (0.36)
0.10
...median [IQR]
0.99 [0.82, 1.25]
0.97 [0.80, 1.20]
0.05
0.99 [0.82, 1.18]
0.97 [0.80, 1.14]
0.05
N/A
N/A
#VALUE!
0.99 (0.42)
0.97 (0.36)
0.05
...Missing; n (%)
84,934 (61.7%)
11,804 (60.7%)
0.02
135,056 (94.2%)
19,899 (94.6%)
-0.02
N/A
N/A
#VALUE!
219,990 (78.3%)
31,703 (78.3%)
0.00
Lab result number- HDL level (mg/dl) mean (only =<5000 
included) 
                                          43,367                                              6,185 
                                             7,424                                              1,042 
N/A
N/A
                                          50,791                                              7,227 
...mean (sd)
47.10 (13.82)
45.86 (13.11)
0.09
45.00 (14.90)
44.44 (13.95)
0.04
N/A
N/A
#VALUE!
46.79 (13.98)
45.66 (13.24)
0.08
...median [IQR]
45.00 [38.00, 54.00]
44.00 [37.00, 53.00]
0.07
43.50 [36.00, 52.00]
43.00 [36.00, 52.00]
0.03
N/A
N/A
#VALUE!
44.78 (13.98)
43.86 (13.24)
0.07
...Missing; n (%)
94,282 (68.5%)
13,275 (68.2%)
0.01
135,913 (94.8%)
19,999 (95.0%)
-0.01
N/A
N/A
#VALUE!
230,195 (81.9%)
33,274 (82.2%)
-0.01
Lab result number- LDL level (mg/dl) mean (only =<5000 
included) 
                                          43,555                                              6,264 
                                             7,261                                                  970 
N/A
N/A
                                          50,816                                              7,234 
...mean (sd)
84.65 (36.88)
82.02 (37.07)
0.07
85.59 (39.45)
83.80 (40.29)
0.04
N/A
N/A
#VALUE!
84.78 (37.26)
82.26 (37.52)
0.07
...median [IQR]
81.00 [62.00, 105.00]
79.00 [60.00, 102.00]
0.05
83.00 [63.00, 108.00]
83.83 [62.00, 106.00]
-0.02
N/A
N/A
#VALUE!
81.29 (37.26)
79.65 (37.52)
0.04
...Missing; n (%)
94,094 (68.4%)
13,196 (67.8%)
0.01
136,076 (94.9%)
20,071 (95.4%)
-0.02
N/A
N/A
#VALUE!
230,170 (81.9%)
33,267 (82.1%)
-0.01
Lab result number- Total cholesterol (mg/dl) mean (only 
=<5000 included) 
                                          43,788                                              6,307 
                                             7,574                                              1,055 
N/A
N/A
                                          51,362                                              7,362 
...mean (sd)
168.90 (43.18)
167.72 (42.61)
0.03
169.13 (49.20)
170.60 (48.43)
-0.03
N/A
N/A
#VALUE!
168.93 (44.12)
168.13 (43.49)
0.02
...median [IQR]
163.00 [140.00, 192.00]
162.00 [139.00, 191.00]
0.02
165.50 [141.00, 195.00]
166.00 [143.00, 196.00]
-0.01
N/A
N/A
#VALUE!
163.37 (44.12)
162.57 (43.49)
0.02
...Missing; n (%)
93,861 (68.2%)
13,153 (67.6%)
0.01
135,763 (94.7%)
19,986 (95.0%)
-0.01
N/A
N/A
#VALUE!
229,624 (81.7%)
33,139 (81.8%)
0.00
Lab result number- Triglyceride level (mg/dl) mean (only 
=<5000 included) 
                                          43,537                                              6,253 
                                             7,487                                              1,037 
N/A
N/A
                                          51,024                                              7,290 
...mean (sd)
174.08 (126.30)
184.98 (134.65)
-0.08
177.97 (145.09)
188.26 (149.15)
-0.07
N/A
N/A
#VALUE!
174.65 (129.23)
185.45 (136.81)
-0.08
...median [IQR]
147.00 [106.00, 207.00]
155.00 [112.00, 218.25]
-0.06
147.00 [104.00, 211.00]
155.00 [108.75, 222.50]
-0.05
N/A
N/A
#VALUE!
147.00 (129.23)
155.00 (136.81)
-0.06
...Missing; n (%)
94,112 (68.4%)
13,207 (67.9%)
0.01
135,850 (94.8%)
20,004 (95.1%)
-0.01
N/A
N/A
#VALUE!
229,962 (81.8%)
33,211 (82.0%)
-0.01
Lab result number- Hemoglobin mean (only >0 included)
                                          37,026                                              5,160 
                                             5,743                                                  800 
N/A
N/A
                                          42,769                                              5,960 
...mean (sd)
13.23 (1.68)
13.43 (1.61)
-0.12
6,480.13 (237,920.16)
13.29 (2.45)
0.04
N/A
N/A
#VALUE!
881.60 (87179.33)
13.41 (1.75)
0.01
...median [IQR]
13.30 [12.10, 14.40]
13.40 [12.40, 14.50]
-0.06
13.43 [12.30, 14.60]
13.45 [12.40, 14.70]
0.00
N/A
N/A
#VALUE!
#VALUE!
13.41 (1.75)
#VALUE!
...Missing; n (%)
100,623 (73.1%)
14,300 (73.5%)
-0.01
137,594 (96.0%)
20,241 (96.2%)
-0.01
N/A
N/A
#VALUE!
238,217 (84.8%)
34,541 (85.3%)
-0.01
Lab result number- Serum sodium mean (only > 90 and < 
190 included)
                                          51,647                                              7,503 
                                             8,075                                              1,118 
N/A
N/A
                                          59,722                                              8,621 
...mean (sd)
139.46 (2.75)
139.63 (2.63)
-0.06
139.06 (2.61)
139.07 (2.53)
0.00
N/A
N/A
#VALUE!
139.41 (2.73)
139.56 (2.62)
-0.06
...median [IQR]
139.67 [138.00, 141.00]
140.00 [138.00, 141.33]
-0.12
139.00 [137.50, 141.00]
139.00 [137.50, 141.00]
0.00
N/A
N/A
#VALUE!
139.58 (2.73)
139.87 (2.62)
-0.11
...Missing; n (%)
86,002 (62.5%)
11,957 (61.4%)
0.02
135,262 (94.4%)
19,923 (94.7%)
-0.01
N/A
N/A
#VALUE!
221,264 (78.7%)
31,880 (78.7%)
0.00
Lab result number- Albumin mean (only >0 and <=10 
included)
                                          48,037                                              6,977 
                                             7,159                                              1,043 
N/A
N/A
                                          55,196                                              8,020 
...mean (sd)
4.23 (0.32)
4.22 (0.31)
0.03
4.15 (0.61)
4.10 (0.69)
0.08
N/A
N/A
#VALUE!
4.22 (0.37)
4.20 (0.38)
0.05
...median [IQR]
4.25 [4.03, 4.40]
4.20 [4.00, 4.40]
0.16
4.20 [4.00, 4.43]
4.20 [4.00, 4.40]
0.00
N/A
N/A
#VALUE!
4.24 (0.37)
4.20 (0.38)
0.11
...Missing; n (%)
89,612 (65.1%)
12,483 (64.1%)
0.02
136,178 (95.0%)
19,998 (95.0%)
0.00
N/A
N/A
#VALUE!
225,790 (80.4%)
32,481 (80.2%)
0.01
Lab result number- Glucose (fasting or random) mean 
(only 10-1000 included)
                                          51,675                                              7,479 
                                             7,923                                              1,101 
N/A
N/A
                                          59,598                                              8,580 
...mean (sd)
165.49 (64.13)
166.85 (68.45)
-0.02
166.86 (64.34)
167.95 (68.62)
-0.02
N/A
N/A
#VALUE!
165.67 (64.16)
166.99 (68.48)
-0.02
...median [IQR]
151.00 [123.00, 191.00]
151.33 [119.00, 196.50]
0.00
152.00 [123.50, 193.00]
152.00 [119.00, 197.50]
0.00
N/A
N/A
#VALUE!
151.13 (64.16)
151.42 (68.48)
0.00
...Missing; n (%)
85,974 (62.5%)
11,981 (61.6%)
0.02
135,414 (94.5%)
19,940 (94.8%)
-0.01
N/A
N/A
#VALUE!
221,388 (78.8%)
31,921 (78.8%)
0.00
Lab result number- Potassium mean (only 1-7 included)
                                          52,631                                              7,654 
                                             8,344                                              1,170 
N/A
N/A
                                          60,975                                              8,824 
...mean (sd)
4.46 (0.45)
4.46 (0.43)
0.00
4.38 (0.45)
4.36 (0.46)
0.04
N/A
N/A
#VALUE!
4.45 (0.45)
4.45 (0.43)
0.00
...median [IQR]
4.45 [4.20, 4.70]
4.45 [4.20, 4.70]
0.00
4.40 [4.10, 4.65]
4.35 [4.00, 4.60]
0.11
N/A
N/A
#VALUE!
4.44 (0.45)
4.44 (0.43)
0.00
...Missing; n (%)
85,018 (61.8%)
11,806 (60.7%)
0.02
134,993 (94.2%)
19,871 (94.4%)
-0.01
N/A
N/A
#VALUE!
220,011 (78.3%)
31,677 (78.2%)
0.00
Comorbidity Scores
CCI (180 days)- ICD9 and ICD10 
...mean (sd)
2.97 (2.15)
2.83 (1.89)
0.07
2.25 (1.79)
2.11 (1.55)
0.08
3.28 (2.42)
2.88 (1.99)
0.18
3.02 (2.26)
2.68 (1.87)
0.16
...median [IQR]
2.00 [1.00, 4.00]
2.00 [1.00, 4.00]
0.00
2.00 [1.00, 3.00]
2.00 [1.00, 3.00]
0.00
3.00 [1.00, 4.00]
2.00 [1.00, 4.00]
0.45
2.62 (2.26)
2.00 (1.87)
0.30
Frailty Score: Qualitative Version 365 days as Categories, 
v1
...0; n (%)
58,642 (42.6%)
9,778 (50.2%)
-0.15
42,071 (29.4%)
6,451 (30.7%)
-0.03
124,218 (27.3%)
15,058 (33.6%)
-0.14
224,931 (30.6%)
31,287 (36.7%)
-0.13
...1 to 2; n (%)
48,415 (35.2%)
6,258 (32.2%)
0.06
62,110 (43.3%)
9,391 (44.6%)
-0.03
154,631 (34.0%)
15,118 (33.8%)
0.00
265,156 (36.0%)
30,767 (36.1%)
0.00
...3 or more; n (%)
30,592 (22.2%)
3,424 (17.6%)
0.12
39,156 (27.3%)
5,199 (24.7%)
0.06
175,851 (38.7%)
14,602 (32.6%)
0.13
245,599 (33.4%)
23,225 (27.2%)
0.14
Frailty Score: Empirical Version 365 days as Categories, 
...< 0.12908; n (%)
26,302 (19.1%)
3,419 (17.6%)
0.04
25,022 (17.5%)
3,502 (16.6%)
0.02
40,499 (8.9%)
4,069 (9.1%)
-0.01
91,823 (12.5%)
10,990 (12.9%)
-0.01
...0.12908 - 0.1631167; n (%)
43,259 (31.4%)
6,091 (31.3%)
0.00
45,778 (31.9%)
6,848 (32.5%)
-0.01
100,081 (22.0%)
10,744 (24.0%)
-0.05
189,118 (25.7%)
23,683 (27.8%)
-0.05
...>= 0.1631167; n (%)
68,088 (49.5%)
9,950 (51.1%)
-0.03
72,537 (50.6%)
10,691 (50.8%)
0.00
314,120 (69.1%)
29,965 (66.9%)
0.05
454,745 (61.8%)
50,606 (59.3%)
0.05
Non-Frailty; n (%)
82,389 (59.9%)
12,060 (62.0%)
-0.04
77,838 (54.3%)
11,838 (56.3%)
-0.04
18,822 (4.1%)
1,899 (4.2%)
-0.01
179,049 (24.3%)
25,797 (30.3%)
-0.13
Frailty Score (mean): Qualitative Version 365 days, v1
...mean (sd)
1.52 (2.04)
1.19 (1.72)
0.17
1.82 (1.97)
1.65 (1.71)
0.09
2.43 (2.56)
1.96 (2.17)
0.20
2.14 (2.36)
1.71 (1.97)
0.20
...median [IQR]
1.00 [0.00, 2.00]
0.00 [0.00, 2.00]
0.53
1.00 [0.00, 3.00]
1.00 [0.00, 2.00]
0.00
2.00 [0.00, 4.00]
1.00 [0.00, 3.00]
0.42
1.62 (2.36)
0.77 (1.97)
0.39
Frailty Score (mean): Empirical Version 365 days, 
...mean (sd)
0.18 (0.06)
0.18 (0.05)
0.00
0.17 (0.05)
0.17 (0.05)
0.00
0.21 (0.07)
0.20 (0.06)
0.15
0.20 (0.06)
0.19 (0.06)
0.17
...median [IQR]
0.16 [0.14, 0.20]
0.16 [0.14, 0.20]
0.00
0.16 [0.13, 0.19]
0.16 [0.13, 0.19]
0.00
0.19 [0.15, 0.24]
0.18 [0.15, 0.23]
0.15
0.18 (0.06)
0.17 (0.06)
0.17
Table 1: Liraglutide vs DPP4i

Healthcare Utilization
Any hospitalization; n (%)
15,411 (11.2%)
1,572 (8.1%)
17,629 (12.3%)
1,789 (8.5%)
69,335 (15.2%)
3,966 (8.9%)
102,375 (13.9%)
7,327 (8.6%)
0.17
Any hospitalization within prior 30 days; n (%)
5,707 (4.1%)
323 (1.7%)
5,387 (3.8%)
318 (1.5%)
25,040 (5.5%)
770 (1.7%)
36,134 (4.9%)
1,411 (1.7%)
0.18
Any hospitalization during prior 31-180 days; n (%)
10,885 (7.9%)
1,314 (6.8%)
13,146 (9.2%)
1,527 (7.3%)
51,026 (11.2%)
3,341 (7.5%)
75,057 (10.2%)
6,182 (7.2%)
0.11
Endocrinologist Visit; n (%)
12,664 (9.2%)
4,174 (21.4%)
14,144 (9.9%)
4,761 (22.6%)
50,811 (11.2%)
11,071 (24.7%)
77,619 (10.6%)
20,006 (23.5%)
-0.35
Endocrinologist Visit (30 days prior); n (%)
8,050 (5.8%)
2,703 (13.9%)
9,334 (6.5%)
3,309 (15.7%)
32,372 (7.1%)
7,011 (15.7%)
49,756 (6.8%)
13,023 (15.3%)
-0.27
Endocrinologist Visit (31 to 180 days prior); n (%)
8,644 (6.3%)
2,970 (15.3%)
9,648 (6.7%)
3,342 (15.9%)
35,496 (7.8%)
8,312 (18.6%)
53,788 (7.3%)
14,624 (17.1%)
-0.30
Internal medicine/family medicine visits; n (%)
121,361 (88.2%)
16,269 (83.6%)
124,756 (87.0%)
18,034 (85.7%)
387,047 (85.1%)
37,552 (83.9%)
633,164 (86.1%)
71,855 (84.3%)
0.05
Internal medicine/family medicine visits (30 days prior) ; 
n (%)
94,520 (68.7%)
11,561 (59.4%)
94,848 (66.2%)
12,851 (61.1%)
290,265 (63.8%)
25,156 (56.2%)
479,633 (65.2%)
49,568 (58.1%)
0.15
Internal medicine/family medicine visits (31 to 180 days 
prior) ; n (%)
110,003 (79.9%)
14,957 (76.9%)
111,872 (78.0%)
16,418 (78.0%)
347,879 (76.5%)
34,444 (76.9%)
569,754 (77.4%)
65,819 (77.2%)
0.00
Cardiologist visit; n (%)
45,210 (32.8%)
6,781 (34.8%)
45,236 (31.6%)
7,080 (33.6%)
177,196 (39.0%)
16,264 (36.3%)
267,642 (36.4%)
30,125 (35.3%)
0.02
Number of Cardiologist visits (30 days prior); n (%)
17,032 (12.4%)
2,281 (11.7%)
16,404 (11.4%)
2,355 (11.2%)
67,756 (14.9%)
5,177 (11.6%)
101,192 (13.8%)
9,813 (11.5%)
0.07
Number of Cardiologist visits (31 to 180 days prior); n (%)
38,027 (27.6%)
5,824 (29.9%)
38,469 (26.8%)
6,074 (28.9%)
152,067 (33.4%)
14,293 (31.9%)
228,563 (31.1%)
26,191 (30.7%)
0.01
Electrocardiogram ; n (%)
49,482 (35.9%)
6,621 (34.0%)
54,504 (38.0%)
7,572 (36.0%)
181,062 (39.8%)
15,773 (35.2%)
285,048 (38.7%)
29,966 (35.1%)
0.07
Use of glucose test strips; n (%)
6,117 (4.4%)
808 (4.2%)
5,867 (4.1%)
1,004 (4.8%)
17,314 (3.8%)
1,728 (3.9%)
29,298 (4.0%)
3,540 (4.2%)
-0.01
Dialysis; n (%)
82 (0.1%)
11 (0.1%)
136 (0.1%)
9 (0.0%)
560 (0.1%)
18 (0.0%)
778 (0.1%)
038 (0.0%)
0.04
Naive new user v8 ; n (%)
23,724 (17.2%)
2,950 (15.2%)
23,744 (16.6%)
2,590 (12.3%)
66,532 (14.6%)
4,828 (10.8%)
114,000 (15.5%)
10,368 (12.2%)
0.10
N antidiabetic drugs at index date  
...mean (sd)
2.12 (0.81)
2.07 (0.88)
0.06
2.14 (0.81)
2.10 (0.90)
0.05
2.10 (0.79)
2.11 (0.85)
-0.01
2.11 (0.80)
2.10 (0.87)
0.01
...median [IQR]
2.00 [2.00, 3.00]
2.00 [1.00, 3.00]
0.00
2.00 [2.00, 3.00]
2.00 [1.00, 3.00]
0.00
2.00 [2.00, 3.00]
2.00 [1.00, 3.00]
0.00
2.00 (0.80)
2.00 (0.87)
0.00
number of different/distinct medication prescriptions
...mean (sd)
10.45 (4.75)
11.70 (5.14)
-0.25
10.12 (4.59)
11.57 (4.91)
-0.31
10.69 (4.75)
11.32 (4.71)
-0.13
10.53 (4.72)
11.47 (4.86)
-0.20
...median [IQR]
10.00 [7.00, 13.00]
11.00 [8.00, 15.00]
-0.20
9.00 [7.00, 13.00]
11.00 [8.00, 14.00]
-0.42
10.00 [7.00, 13.00]11.00 [8.00, 14.00]
-0.21
9.81 (4.72)
11.00 (4.86)
-0.25
Number of Hospitalizations
...mean (sd)
0.14 (0.46)
0.10 (0.36)
0.10
0.15 (0.43)
0.10 (0.35)
0.13
0.22 (0.61)
0.11 (0.40)
0.21
0.19 (0.55)
0.11 (0.38)
0.17
...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, 0.00]
0.00
0.00 (0.55)
0.00 (0.38)
0.00
Number of hospital days
...mean (sd)
0.89 (4.08)
0.49 (2.57)
0.12
0.88 (4.03)
0.47 (2.29)
0.13
1.51 (5.72)
0.63 (2.98)
0.19
1.27 (5.15)
0.56 (2.73)
0.17
...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, 0.00]
0.00
0.00 (5.15)
0.00 (2.73)
0.00
Number of Emergency Department (ED) visits 
...mean (sd)
0.47 (1.31)
0.41 (1.20)
0.05
0.23 (1.55)
0.16 (1.24)
0.05
0.64 (1.56)
0.45 (1.22)
0.14
0.53 (1.51)
0.37 (1.22)
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, 0.00]
0.00
0.00 (1.51)
0.00 (1.22)
0.00
Number of Office visits
...mean (sd)
5.26 (3.96)
5.84 (4.12)
-0.14
5.47 (4.09)
6.07 (4.31)
-0.14
5.82 (4.49)
6.47 (4.62)
-0.14
5.65 (4.32)
6.23 (4.43)
-0.13
...median [IQR]
4.00 [3.00, 7.00]
5.00 [3.00, 8.00]
-0.25
4.00 [3.00, 7.00]
5.00 [3.00, 8.00]
-0.24
5.00 [3.00, 8.00]
5.00 [3.00, 8.00]
0.00
4.62 (4.32)
5.00 (4.43)
-0.09
Number of Endocrinologist visits
...mean (sd)
0.43 (2.15)
1.12 (3.61)
-0.23
0.46 (2.24)
1.18 (3.69)
-0.24
0.64 (3.15)
1.63 (5.11)
-0.23
0.57 (2.82)
1.40 (4.48)
-0.22
...median [IQR]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00
0.00 (2.82)
0.00 (4.48)
0.00
Number of internal medicine/family medicine visits
...mean (sd)
11.36 (14.86)
10.41 (14.29)
0.07
8.00 (10.30)
7.77 (9.67)
0.02
9.44 (12.00)
8.75 (11.42)
0.06
9.52 (12.29)
8.89 (11.75)
0.05
...median [IQR]
7.00 [3.00, 15.00]
6.00 [2.00, 13.00]
0.07
5.00 [2.00, 10.00]
5.00 [2.00, 10.00]
0.00
6.00 [2.00, 13.00] 5.00 [2.00, 12.00]
0.09
5.99 (12.29)
5.23 (11.75)
0.06
Number of Cardiologist visits
...mean (sd)
1.74 (4.43)
1.71 (4.03)
0.01
1.49 (3.77)
1.54 (3.73)
-0.01
2.31 (5.55)
1.97 (4.90)
0.06
2.04 (5.05)
1.80 (4.44)
0.05
...median [IQR]
0.00 [0.00, 1.00]
0.00 [0.00, 2.00]
0.00
0.00 [0.00, 1.00]
0.00 [0.00, 2.00]
0.00
0.00 [0.00, 2.00]
0.00 [0.00, 2.00]
0.00
0.00 (5.05)
0.00 (4.44)
0.00
Number electrocardiograms received 
...mean (sd)
0.76 (1.64)
0.67 (1.47)
0.06
0.71 (1.34)
0.64 (1.21)
0.05
0.89 (1.66)
0.70 (1.34)
0.13
0.83 (1.60)
0.68 (1.34)
0.10
...median [IQR]
0.00 [0.00, 1.00]
0.00 [0.00, 1.00]
0.00
0.00 [0.00, 1.00]
0.00 [0.00, 1.00]
0.00
0.00 [0.00, 1.00]
0.00 [0.00, 1.00]
0.00
0.00 (1.60)
0.00 (1.34)
0.00
Number of HbA1c tests ordered
...mean (sd)
1.35 (0.93)
1.40 (0.92)
-0.05
0.98 (0.94)
1.15 (0.95)
-0.18
1.44 (0.91)
1.53 (0.88)
-0.10
1.33 (0.92)
1.41 (0.91)
-0.09
...median [IQR]
1.00 [1.00, 2.00]
1.00 [1.00, 2.00]
0.00
1.00 [0.00, 2.00]
1.00 [0.00, 2.00]
0.00
1.00 [1.00, 2.00]
1.00 [1.00, 2.00]
0.00
1.00 (0.92)
1.00 (0.91)
0.00
Number of glucose tests ordered
...mean (sd)
0.60 (2.85)
0.57 (1.41)
0.01
0.43 (1.50)
0.50 (1.20)
-0.05
0.49 (1.20)
0.51 (1.13)
-0.02
0.50 (1.69)
0.52 (1.22)
-0.01
...median [IQR]
0.00 [0.00, 0.00]
0.00 [0.00, 1.00]
0.00
0.00 [0.00, 0.00]
0.00 [0.00, 1.00]
0.00
0.00 [0.00, 1.00]
0.00 [0.00, 1.00]
0.00
0.00 (1.69)
0.00 (1.22)
0.00
Number of lipid tests ordered
...mean (sd)
1.08 (1.01)
1.08 (1.01)
0.00
0.86 (1.31)
1.00 (1.31)
-0.11
1.07 (0.86)
1.11 (0.88)
-0.05
1.03 (0.99)
1.08 (1.03)
-0.05
...median [IQR]
1.00 [0.00, 2.00]
1.00 [0.00, 2.00]
0.00
1.00 [0.00, 1.00]
1.00 [0.00, 1.00]
0.00
1.00 [0.00, 2.00]
1.00 [1.00, 2.00]
0.00
1.00 (0.99)
1.00 (1.03)
0.00
Number of creatinine tests ordered
...mean (sd)
0.06 (0.35)
0.06 (0.30)
0.00
0.06 (0.35)
0.06 (0.34)
0.00
0.09 (0.39)
0.10 (0.41)
-0.02
0.08 (0.38)
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, 0.00]
0.00
0.00 (0.38)
0.00 (0.37)
0.00
Number of BUN tests ordered
...mean (sd)
0.04 (0.28)
0.03 (0.23)
0.04
0.04 (0.29)
0.04 (0.27)
0.00
0.06 (0.32)
0.06 (0.32)
0.00
0.05 (0.31)
0.05 (0.29)
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, 0.00]
0.00
0.00 (0.31)
0.00 (0.29)
0.00
Number of tests for microalbuminuria
...mean (sd)
0.82 (1.23)
0.87 (1.25)
-0.04
0.52 (0.99)
0.64 (1.07)
-0.12
0.49 (0.73)
0.56 (0.77)
-0.09
0.56 (0.90)
0.65 (0.97)
-0.10
...median [IQR]
0.00 [0.00, 2.00]
0.00 [0.00, 2.00]
0.00
0.00 [0.00, 1.00]
0.00 [0.00, 1.00]
0.00
0.00 [0.00, 1.00]
0.00 [0.00, 1.00]
0.00
0.00 (0.90)
0.00 (0.97)
0.00
Total N distinct ICD9/ICD10 diagnoses at the 3rd digit 
level 
...mean (sd)
5.98 (8.59)
7.00 (8.44)
-0.12
2.59 (5.59)
2.39 (4.66)
0.04
6.46 (9.71)
6.21 (8.58)
0.03
5.62 (8.84)
5.45 (7.76)
0.02
...median [IQR]
4.00 [0.00, 9.00]
5.00 [0.00, 10.00]
-0.12
0.00 [0.00, 4.00]
0.00 [0.00, 4.00]
0.00
3.00 [0.00, 9.00] 3.00 [0.00, 10.00]
0.00
2.60 (8.84)
2.72 (7.76)
-0.01
Use of thiazide; n (%)
19,082 (13.9%)
2,749 (14.1%)
-0.005763928
18,570 (13.0%)
2,811 (13.4%)
-0.01181737
66,785 (14.7%)
6,981 (15.6%)
-0.02510409
104,437 (14.2%)
12,541 (14.7%)
-0.01
Use of beta blockers; n (%)
62,221 (45.2%)
8,804 (45.2%)
0.00
67,518 (47.1%)
9,653 (45.9%)
0.02
233,117 (51.3%)
21,826 (48.7%)
0.05
362,856 (49.3%)
40,283 (47.2%)
0.04
Use of calcium channel blockers; n (%)
46,524 (33.8%)
5,822 (29.9%)
0.08
46,777 (32.6%)
6,355 (30.2%)
0.05
167,449 (36.8%)
14,468 (32.3%)
0.09
260,750 (35.4%)
26,645 (31.2%)
0.09
Table 1: Liraglutide vs DPP4i

Variable
Reference- DPP4i
Exposure- Liraglutide
St. Diff.
Reference- DPP4i
Exposure- Liraglutide
St. Diff.
Reference- DPP4i
Exposure- Liraglutide
St. Diff.
Reference- DPP4i
Exposure- Liraglutide
St. Diff.
Number of patients
19187
19187
20777
20777
44381
44381
                                          84,345                                           84,345 
Age
...mean (sd)
65.88 (7.35)
66.08 (6.82)
-0.03
62.98 (6.89)
63.12 (6.32)
-0.02
70.54 (5.22)
70.62 (5.01)
-0.02
67.62 (6.19)
67.74 (5.80)
-0.02
...median [IQR]
66.00 [61.00, 70.00]
66.00 [61.00, 70.00]
0.00
62.00 [60.00, 66.00]
62.00 [60.00, 66.00]
0.00
69.00 [67.00, 73.00]
69.00 [67.00, 73.00]
0.00
66.59 (6.19)
66.59 (5.80)
0.00
Age categories 
...18 - 54; n (%)
1,284 (6.7%)
1,036 (5.4%)
0.05
2,089 (10.1%)
1,724 (8.3%)
0.06
0 (0.0%)
0 (0.0%)
#DIV/0!
3,373 (4.0%)
2,760 (3.3%)
0.04
...55 - 64; n (%)
6,997 (36.5%)
6,760 (35.2%)
0.03
12,548 (60.4%)
12,685 (61.1%)
-0.01
1,434 (3.2%)
1,078 (2.4%)
0.05
20,979 (24.9%)
20,523 (24.3%)
0.01
...65 - 74; n (%)
8,588 (44.8%)
9,298 (48.5%)
-0.07
4,672 (22.5%)
5,162 (24.8%)
-0.05
34,293 (77.3%)
34,597 (78.0%)
-0.02
47,553 (56.4%)
49,057 (58.2%)
-0.04
...>= 75; n (%)
2,318 (12.1%)
2,093 (10.9%)
0.04
1,468 (7.1%)
1,206 (5.8%)
0.05
8,654 (19.5%)
8,706 (19.6%)
0.00
12,440 (14.7%)
12,005 (14.2%)
0.01
Gender - United
...Males; n (%)
9,107 (47.5%)
9,089 (47.4%)
0.00
10,509 (50.6%)
10,673 (51.4%)
-0.02
19,489 (43.9%)
19,600 (44.2%)
-0.01
39,105 (46.4%)
39,362 (46.7%)
-0.01
...Females; n (%)
10,080 (52.5%)
10,098 (52.6%)
0.00
10,268 (49.4%)
10,104 (48.6%)
0.02
24,892 (56.1%)
24,781 (55.8%)
0.01
45,240 (53.6%)
44,983 (53.3%)
0.01
Race 
...White; n (%)
N/A
N/A
N/A
N/A
38,069 (85.8%)
37,846 (85.3%)
0.01
38,069 (85.8%)
37,846 (85.3%)
0.01
...Black; n (%)
N/A
N/A
N/A
N/A
3,578 (8.1%)
3,789 (8.5%)
-0.01
3,578 (8.1%)
3,789 (8.5%)
-0.01
...Asian; n (%)
N/A
N/A
N/A
N/A
464 (1.0%)
531 (1.2%)
-0.02
464 (1.0%)
531 (1.2%)
-0.02
...Hispanic; n (%)
N/A
N/A
N/A
N/A
837 (1.9%)
801 (1.8%)
0.01
837 (1.9%)
801 (1.8%)
0.01
...North American Native; n (%)
N/A
N/A
N/A
N/A
179 (0.4%)
177 (0.4%)
0.00
179 (0.4%)
177 (0.4%)
0.00
...Other/Unknown; n (%)
N/A
N/A
N/A
N/A
1,254 (2.8%)
1,237 (2.8%)
0.00
1,254 (2.8%)
1,237 (2.8%)
0.00
Region - United  (lumping missing&other category 
with West)
...Northeast; n (%)
1,677 (8.7%)
1,736 (9.0%)
-0.01
3,838 (18.5%)
3,945 (19.0%)
-0.01
6,816 (15.4%)
6,961 (15.7%)
-0.01
12,331 (14.6%)
12,642 (15.0%)
-0.01
...South; n (%)
10,357 (54.0%)
10,229 (53.3%)
0.01
4,513 (21.7%)
4,504 (21.7%)
0.00
20,540 (46.3%)
20,477 (46.1%)
0.00
35,410 (42.0%)
35,210 (41.7%)
0.01
...Midwest; n (%)
3,728 (19.4%)
3,773 (19.7%)
-0.01
9,878 (47.5%)
9,791 (47.1%)
0.01
10,234 (23.1%)
10,227 (23.0%)
0.00
23,840 (28.3%)
23,791 (28.2%)
0.00
...West; n (%)
3,425 (17.9%)
3,449 (18.0%)
0.00
2,326 (11.2%)
2,314 (11.1%)
0.00
6,791 (15.3%)
6,716 (15.1%)
0.01
12,542 (14.9%)
12,479 (14.8%)
0.00
...Unknown+missing; n (%)
N/A
N/A
#VALUE!
222 (1.1%)
223 (1.1%)
0.00
N/A
N/A
#VALUE!
222 (1.1%)
223 (1.1%)
0.00
CV Covariates
Ischemic heart disease; n (%)
5,701 (29.7%)
5,722 (29.8%)
6,791 (32.7%)
6,767 (32.6%)
13,769 (31.0%)
13,776 (31.0%)
26,261 (31.1%)
26,265 (31.1%)
0.00
Acute MI; n (%)
291 (1.5%)
290 (1.5%)
311 (1.5%)
306 (1.5%)
554 (1.2%)
535 (1.2%)
1,156 (1.4%)
1,131 (1.3%)
0.01
ACS/unstable angina; n (%)
370 (1.9%)
389 (2.0%)
429 (2.1%)
429 (2.1%)
814 (1.8%)
739 (1.7%)
1,613 (1.9%)
1,557 (1.8%)
0.01
Old MI; n (%)
794 (4.1%)
770 (4.0%)
403 (1.9%)
428 (2.1%)
1,598 (3.6%)
1,594 (3.6%)
2,795 (3.3%)
2,792 (3.3%)
0.00
Stable angina; n (%)
912 (4.8%)
931 (4.9%)
730 (3.5%)
742 (3.6%)
1,771 (4.0%)
1,708 (3.8%)
3,413 (4.0%)
3,381 (4.0%)
0.00
Coronary atherosclerosis and other forms of chronic 
ischemic heart disease; n (%)
5,358 (27.9%)
5,377 (28.0%)
6,498 (31.3%)
6,468 (31.1%)
13,175 (29.7%)
13,182 (29.7%)
25,031 (29.7%)
25,027 (29.7%)
0.00
Other atherosclerosis with ICD10  ; n (%)
184 (1.0%)
201 (1.0%)
240 (1.2%)
238 (1.1%)
683 (1.5%)
756 (1.7%)
1,107 (1.3%)
1,195 (1.4%)
-0.01
Previous cardiac procedure (CABG or PTCA or Stent) ; 
n (%)
168 (0.9%)
173 (0.9%)
221 (1.1%)
211 (1.0%)
300 (0.7%)
233 (0.5%)
689 (0.8%)
617 (0.7%)
0.01
History of CABG or PTCA; n (%)
1,375 (7.2%)
1,387 (7.2%)
840 (4.0%)
825 (4.0%)
3,726 (8.4%)
3,698 (8.3%)
5,941 (7.0%)
5,910 (7.0%)
0.00
Any stroke; n (%)
1,414 (7.4%)
1,401 (7.3%)
1,494 (7.2%)
1,500 (7.2%)
3,852 (8.7%)
3,786 (8.5%)
6,760 (8.0%)
6,687 (7.9%)
0.00
Ischemic stroke (w and w/o mention of cerebral 
infarction); n (%)
1,392 (7.3%)
1,390 (7.2%)
1,476 (7.1%)
1,479 (7.1%)
3,816 (8.6%)
3,753 (8.5%)
6,684 (7.9%)
6,622 (7.9%)
0.00
Hemorrhagic stroke; n (%)
38 (0.2%)
31 (0.2%)
37 (0.2%)
36 (0.2%)
80 (0.2%)
62 (0.1%)
155 (0.2%)
129 (0.2%)
0.00
TIA; n (%)
328 (1.7%)
326 (1.7%)
379 (1.8%)
363 (1.7%)
848 (1.9%)
769 (1.7%)
1,555 (1.8%)
1,458 (1.7%)
0.01
Other cerebrovascular disease; n (%)
355 (1.9%)
330 (1.7%)
255 (1.2%)
237 (1.1%)
883 (2.0%)
895 (2.0%)
1,493 (1.8%)
1,462 (1.7%)
0.01
Late effects of cerebrovascular disease; n (%)
261 (1.4%)
244 (1.3%)
142 (0.7%)
150 (0.7%)
598 (1.3%)
634 (1.4%)
1,001 (1.2%)
1,028 (1.2%)
0.00
Cerebrovascular procedure; n (%)
9 (0.0%)
21 (0.1%)
24 (0.1%)
24 (0.1%)
61 (0.1%)
45 (0.1%)
094 (0.1%)
090 (0.1%)
0.00
Heart failure (CHF); n (%)
2,017 (10.5%)
2,032 (10.6%)
1,594 (7.7%)
1,572 (7.6%)
4,950 (11.2%)
4,901 (11.0%)
8,561 (10.1%)
8,505 (10.1%)
0.00
Peripheral Vascular Disease (PVD) or PVD Surgery ; n 
(%)
1,696 (8.8%)
1,705 (8.9%)
1,697 (8.2%)
1,671 (8.0%)
4,485 (10.1%)
4,556 (10.3%)
7,878 (9.3%)
7,932 (9.4%)
0.00
Atrial fibrillation; n (%)
1,491 (7.8%)
1,541 (8.0%)
1,240 (6.0%)
1,237 (6.0%)
4,728 (10.7%)
4,771 (10.8%)
7,459 (8.8%)
7,549 (9.0%)
-0.01
Other cardiac dysrhythmia; n (%)
2,008 (10.5%)
1,993 (10.4%)
1,498 (7.2%)
1,470 (7.1%)
5,142 (11.6%)
5,106 (11.5%)
8,648 (10.3%)
8,569 (10.2%)
0.00
Cardiac conduction disorders; n (%)
538 (2.8%)
543 (2.8%)
411 (2.0%)
425 (2.0%)
1,563 (3.5%)
1,628 (3.7%)
2,512 (3.0%)
2,596 (3.1%)
-0.01
Other CVD; n (%)
2,256 (11.8%)
2,274 (11.9%)
2,290 (11.0%)
2,252 (10.8%)
6,456 (14.5%)
6,303 (14.2%)
11,002 (13.0%)
10,829 (12.8%)
0.01
Diabetes-related complications
Diabetic retinopathy; n (%)
1,444 (7.5%)
1,474 (7.7%)
989 (4.8%)
1,022 (4.9%)
3,663 (8.3%)
3,676 (8.3%)
6,096 (7.2%)
6,172 (7.3%)
0.00
Diabetes with other ophthalmic manifestations; n 
(%)
143 (0.7%)
140 (0.7%)
678 (3.3%)
726 (3.5%)
1,377 (3.1%)
1,449 (3.3%)
2,198 (2.6%)
2,315 (2.7%)
-0.01
Retinal detachment, vitreous hemorrhage, 
vitrectomy; n (%)
104 (0.5%)
83 (0.4%)
102 (0.5%)
71 (0.3%)
219 (0.5%)
192 (0.4%)
425 (0.5%)
346 (0.4%)
0.01
Retinal laser coagulation therapy; n (%)
128 (0.7%)
120 (0.6%)
149 (0.7%)
137 (0.7%)
350 (0.8%)
289 (0.7%)
627 (0.7%)
546 (0.6%)
0.01
Occurrence of Diabetic Neuropathy  ; n (%)
4,593 (23.9%)
4,623 (24.1%)
2,969 (14.3%)
2,964 (14.3%)
10,346 (23.3%)
10,291 (23.2%)
17,908 (21.2%)
17,878 (21.2%)
0.00
Occurrence of diabetic nephropathy  with ICD10 ; n 
(%)
3,404 (17.7%)
3,439 (17.9%)
1,655 (8.0%)
1,662 (8.0%)
5,588 (12.6%)
5,562 (12.5%)
10,647 (12.6%)
10,663 (12.6%)
0.00
Hypoglycemia ; n (%)
476 (2.5%)
476 (2.5%)
606 (2.9%)
625 (3.0%)
1,381 (3.1%)
1,358 (3.1%)
2,463 (2.9%)
2,459 (2.9%)
0.00
Hyperglycemia; n (%)
754 (3.9%)
747 (3.9%)
547 (2.6%)
546 (2.6%)
1,711 (3.9%)
1,673 (3.8%)
3,012 (3.6%)
2,966 (3.5%)
0.01
Disorders of fluid electrolyte and acid-base balance; n 
(%)
1,297 (6.8%)
1,346 (7.0%)
986 (4.7%)
950 (4.6%)
3,358 (7.6%)
3,341 (7.5%)
5,641 (6.7%)
5,637 (6.7%)
0.00
Diabetic ketoacidosis; n (%)
25 (0.1%)
21 (0.1%)
29 (0.1%)
20 (0.1%)
61 (0.1%)
53 (0.1%)
115 (0.1%)
094 (0.1%)
0.00
Hyperosmolar hyperglycemic nonketotic syndrome 
(HONK); n (%)
94 (0.5%)
95 (0.5%)
80 (0.4%)
73 (0.4%)
194 (0.4%)
193 (0.4%)
368 (0.4%)
361 (0.4%)
0.00
Diabetes with peripheral circulatory disorders with 
ICD-10  ; n (%)
1,565 (8.2%)
1,519 (7.9%)
831 (4.0%)
871 (4.2%)
3,179 (7.2%)
3,210 (7.2%)
5,575 (6.6%)
5,600 (6.6%)
0.00
Diabetic Foot; n (%)
499 (2.6%)
494 (2.6%)
490 (2.4%)
483 (2.3%)
1,340 (3.0%)
1,361 (3.1%)
2,329 (2.8%)
2,338 (2.8%)
0.00
Gangrene ; n (%)
61 (0.3%)
48 (0.3%)
39 (0.2%)
33 (0.2%)
80 (0.2%)
83 (0.2%)
180 (0.2%)
164 (0.2%)
0.00
 PS-matched
MarketScan
Medicare
POOLED
Optum
Table 1: Liraglutide vs DPP4i

Lower extremity amputation; n (%)
173 (0.9%)
146 (0.8%)
75 (0.4%)
69 (0.3%)
230 (0.5%)
228 (0.5%)
478 (0.6%)
443 (0.5%)
0.01
Osteomyelitis; n (%)
136 (0.7%)
110 (0.6%)
127 (0.6%)
119 (0.6%)
259 (0.6%)
225 (0.5%)
522 (0.6%)
454 (0.5%)
0.01
Skin infections ; n (%)
1,175 (6.1%)
1,153 (6.0%)
1,262 (6.1%)
1,283 (6.2%)
3,424 (7.7%)
3,359 (7.6%)
5,861 (6.9%)
5,795 (6.9%)
0.00
Erectile dysfunction; n (%)
561 (2.9%)
589 (3.1%)
532 (2.6%)
525 (2.5%)
1,286 (2.9%)
1,306 (2.9%)
2,379 (2.8%)
2,420 (2.9%)
-0.01
Diabetes with unspecified complication; n (%)
1,183 (6.2%)
1,212 (6.3%)
1,013 (4.9%)
998 (4.8%)
2,448 (5.5%)
2,456 (5.5%)
4,644 (5.5%)
4,666 (5.5%)
0.00
Diabetes mellitus without mention of complications; 
n (%)
16,719 (87.1%)
16,712 (87.1%)
19,433 (93.5%)
19,456 (93.6%)
41,391 (93.3%)
41,385 (93.2%)
77,543 (91.9%)
77,553 (91.9%)
0.00
Hypertension: 1 inpatient or 2 outpatient claims 
within 365 days; n (%)
18,326 (95.5%)
18,285 (95.3%)
18,379 (88.5%)
18,392 (88.5%)
43,029 (97.0%)
43,046 (97.0%)
79,734 (94.5%)
79,723 (94.5%)
0.00
Hyperlipidemia ; n (%)
15,189 (79.2%)
15,133 (78.9%)
14,678 (70.6%)
14,741 (70.9%)
36,860 (83.1%)
36,848 (83.0%)
66,727 (79.1%)
66,722 (79.1%)
0.00
Edema; n (%)
1,701 (8.9%)
1,712 (8.9%)
1,292 (6.2%)
1,286 (6.2%)
4,774 (10.8%)
4,790 (10.8%)
7,767 (9.2%)
7,788 (9.2%)
0.00
Renal Dysfunction (non-diabetic) ; n (%)
4,574 (23.8%)
4,607 (24.0%)
2,981 (14.3%)
2,999 (14.4%)
9,976 (22.5%)
9,939 (22.4%)
17,531 (20.8%)
17,545 (20.8%)
0.00
Occurrence of acute renal disease ; n (%)
618 (3.2%)
618 (3.2%)
389 (1.9%)
387 (1.9%)
1,410 (3.2%)
1,420 (3.2%)
2,417 (2.9%)
2,425 (2.9%)
0.00
Occurrence of chronic renal insufficiency; n (%)
3,958 (20.6%)
3,966 (20.7%)
2,293 (11.0%)
2,341 (11.3%)
8,564 (19.3%)
8,551 (19.3%)
14,815 (17.6%)
14,858 (17.6%)
0.00
Chronic kidney disease ; n (%)
3,820 (19.9%)
3,855 (20.1%)
2,212 (10.6%)
2,256 (10.9%)
8,088 (18.2%)
8,088 (18.2%)
14,120 (16.7%)
14,199 (16.8%)
0.00
CKD Stage 3-4; n (%)
2,841 (14.8%)
2,830 (14.7%)
1,649 (7.9%)
1,698 (8.2%)
5,873 (13.2%)
5,830 (13.1%)
10,363 (12.3%)
10,358 (12.3%)
0.00
Occurrence of hypertensive nephropathy; n (%)
1,663 (8.7%)
1,699 (8.9%)
836 (4.0%)
857 (4.1%)
3,487 (7.9%)
3,481 (7.8%)
5,986 (7.1%)
6,037 (7.2%)
0.00
Occurrence of miscellaneous renal insufficiency ; n 
(%)
1,009 (5.3%)
1,008 (5.3%)
779 (3.7%)
783 (3.8%)
3,026 (6.8%)
2,878 (6.5%)
4,814 (5.7%)
4,669 (5.5%)
0.01
Glaucoma or cataracts ; n (%)
4,154 (21.7%)
4,031 (21.0%)
3,827 (18.4%)
3,680 (17.7%)
12,558 (28.3%)
12,492 (28.1%)
20,539 (24.4%)
20,203 (24.0%)
0.01
Cellulitis or abscess of toe; n (%)
330 (1.7%)
296 (1.5%)
221 (1.1%)
210 (1.0%)
682 (1.5%)
667 (1.5%)
1,233 (1.5%)
1,173 (1.4%)
0.01
Foot ulcer; n (%)
475 (2.5%)
475 (2.5%)
494 (2.4%)
484 (2.3%)
1,332 (3.0%)
1,339 (3.0%)
2,301 (2.7%)
2,298 (2.7%)
0.00
Bladder stones; n (%)
28 (0.1%)
14 (0.1%)
21 (0.1%)
22 (0.1%)
77 (0.2%)
73 (0.2%)
126 (0.1%)
109 (0.1%)
0.00
Kidney stones; n (%)
473 (2.5%)
461 (2.4%)
528 (2.5%)
512 (2.5%)
1,276 (2.9%)
1,295 (2.9%)
2,277 (2.7%)
2,268 (2.7%)
0.00
Urinary tract infections (UTIs); n (%)
1,744 (9.1%)
1,711 (8.9%)
1,375 (6.6%)
1,356 (6.5%)
5,473 (12.3%)
5,479 (12.3%)
8,592 (10.2%)
8,546 (10.1%)
0.00
Dipstick urinalysis; n (%)
7,240 (37.7%)
6,927 (36.1%)
7,253 (34.9%)
6,731 (32.4%)
18,427 (41.5%)
17,759 (40.0%)
32,920 (39.0%)
31,417 (37.2%)
0.04
Non-dipstick urinalysis; n (%)
8,574 (44.7%)
8,615 (44.9%)
7,423 (35.7%)
7,462 (35.9%)
20,541 (46.3%)
20,649 (46.5%)
36,538 (43.3%)
36,726 (43.5%)
0.00
Urine function test; n (%)
478 (2.5%)
464 (2.4%)
532 (2.6%)
503 (2.4%)
1,674 (3.8%)
1,519 (3.4%)
2,684 (3.2%)
2,486 (2.9%)
0.02
Cytology; n (%)
131 (0.7%)
127 (0.7%)
201 (1.0%)
179 (0.9%)
443 (1.0%)
401 (0.9%)
775 (0.9%)
707 (0.8%)
0.01
Cystos; n (%)
230 (1.2%)
238 (1.2%)
267 (1.3%)
253 (1.2%)
726 (1.6%)
653 (1.5%)
1,223 (1.4%)
1,144 (1.4%)
0.00
Other Covariates
Liver disease; n (%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
000 (0.0%)
000 (0.0%)
#DIV/0!
Osteoarthritis; n (%)
3,745 (19.5%)
3,782 (19.7%)
3,160 (15.2%)
3,192 (15.4%)
10,957 (24.7%)
10,991 (24.8%)
17,862 (21.2%)
17,965 (21.3%)
0.00
Other arthritis, arthropathies and musculoskeletal 
pain; n (%)
7,765 (40.5%)
7,671 (40.0%)
7,650 (36.8%)
7,628 (36.7%)
21,066 (47.5%)
20,955 (47.2%)
36,481 (43.3%)
36,254 (43.0%)
0.01
Dorsopathies; n (%)
5,026 (26.2%)
5,009 (26.1%)
4,446 (21.4%)
4,472 (21.5%)
13,404 (30.2%)
13,332 (30.0%)
22,876 (27.1%)
22,813 (27.0%)
0.00
Fractures; n (%)
523 (2.7%)
543 (2.8%)
528 (2.5%)
524 (2.5%)
1,530 (3.4%)
1,562 (3.5%)
2,581 (3.1%)
2,629 (3.1%)
0.00
Falls ; n (%)
600 (3.1%)
605 (3.2%)
182 (0.9%)
183 (0.9%)
1,506 (3.4%)
1,482 (3.3%)
2,288 (2.7%)
2,270 (2.7%)
0.00
Osteoporosis; n (%)
737 (3.8%)
786 (4.1%)
624 (3.0%)
607 (2.9%)
2,931 (6.6%)
2,880 (6.5%)
4,292 (5.1%)
4,273 (5.1%)
0.00
Hyperthyroidism; n (%)
191 (1.0%)
125 (0.7%)
157 (0.8%)
104 (0.5%)
523 (1.2%)
412 (0.9%)
871 (1.0%)
641 (0.8%)
0.02
Hypothyroidism ; n (%)
3,602 (18.8%)
3,737 (19.5%)
2,944 (14.2%)
2,959 (14.2%)
7,649 (17.2%)
7,701 (17.4%)
14,195 (16.8%)
14,397 (17.1%)
-0.01
Other disorders of thyroid gland ; n (%)
1,019 (5.3%)
969 (5.1%)
999 (4.8%)
991 (4.8%)
2,714 (6.1%)
2,573 (5.8%)
4,732 (5.6%)
4,533 (5.4%)
0.01
Depression; n (%)
2,008 (10.5%)
1,965 (10.2%)
1,630 (7.8%)
1,611 (7.8%)
5,365 (12.1%)
5,264 (11.9%)
9,003 (10.7%)
8,840 (10.5%)
0.01
Anxiety; n (%)
1,752 (9.1%)
1,698 (8.8%)
1,109 (5.3%)
1,066 (5.1%)
3,825 (8.6%)
3,722 (8.4%)
6,686 (7.9%)
6,486 (7.7%)
0.01
Sleep_Disorder; n (%)
2,068 (10.8%)
2,062 (10.7%)
3,430 (16.5%)
3,424 (16.5%)
5,922 (13.3%)
5,843 (13.2%)
11,420 (13.5%)
11,329 (13.4%)
0.00
Dementia; n (%)
389 (2.0%)
405 (2.1%)
209 (1.0%)
211 (1.0%)
1,458 (3.3%)
1,482 (3.3%)
2,056 (2.4%)
2,098 (2.5%)
-0.01
Delirium; n (%)
141 (0.7%)
145 (0.8%)
89 (0.4%)
91 (0.4%)
470 (1.1%)
482 (1.1%)
700 (0.8%)
718 (0.9%)
-0.01
Psychosis; n (%)
140 (0.7%)
131 (0.7%)
82 (0.4%)
80 (0.4%)
430 (1.0%)
410 (0.9%)
652 (0.8%)
621 (0.7%)
0.01
Obesity; n (%)
6,359 (33.1%)
6,321 (32.9%)
4,461 (21.5%)
4,453 (21.4%)
11,476 (25.9%)
11,510 (25.9%)
22,296 (26.4%)
22,284 (26.4%)
0.00
Overweight; n (%)
860 (4.5%)
830 (4.3%)
356 (1.7%)
357 (1.7%)
1,167 (2.6%)
1,226 (2.8%)
2,383 (2.8%)
2,413 (2.9%)
-0.01
Smoking; n (%)
2,270 (11.8%)
2,211 (11.5%)
979 (4.7%)
971 (4.7%)
5,447 (12.3%)
5,371 (12.1%)
8,696 (10.3%)
8,553 (10.1%)
0.01
Alcohol abuse or dependence; n (%)
88 (0.5%)
85 (0.4%)
53 (0.3%)
57 (0.3%)
167 (0.4%)
157 (0.4%)
308 (0.4%)
299 (0.4%)
0.00
Drug abuse or dependence; 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!
COPD; n (%)
1,967 (10.3%)
1,937 (10.1%)
1,281 (6.2%)
1,259 (6.1%)
5,022 (11.3%)
4,898 (11.0%)
8,270 (9.8%)
8,094 (9.6%)
0.01
Asthma; n (%)
1,425 (7.4%)
1,397 (7.3%)
1,264 (6.1%)
1,216 (5.9%)
3,583 (8.1%)
3,478 (7.8%)
6,272 (7.4%)
6,091 (7.2%)
0.01
Obstructive sleep apnea; n (%)
3,445 (18.0%)
3,467 (18.1%)
3,570 (17.2%)
3,587 (17.3%)
6,167 (13.9%)
6,100 (13.7%)
13,182 (15.6%)
13,154 (15.6%)
0.00
Pneumonia; n (%)
431 (2.2%)
430 (2.2%)
407 (2.0%)
407 (2.0%)
1,192 (2.7%)
1,168 (2.6%)
2,030 (2.4%)
2,005 (2.4%)
0.00
Imaging; n (%)
20 (0.1%)
26 (0.1%)
11 (0.1%)
14 (0.1%)
46 (0.1%)
50 (0.1%)
77 (0.1%)
90 (0.1%)
0.00
Diabetes Medications
DM Medications - AGIs; n (%)
94 (0.5%)
99 (0.5%)
78 (0.4%)
81 (0.4%)
273 (0.6%)
253 (0.6%)
445 (0.5%)
433 (0.5%)
0.00
DM Medications - Glitazones; n (%)
2,266 (11.8%)
2,253 (11.7%)
3,295 (15.9%)
3,271 (15.7%)
4,782 (10.8%)
4,697 (10.6%)
10,343 (12.3%)
10,221 (12.1%)
0.01
DM Medications - Insulin; n (%)
3,103 (16.2%)
3,311 (17.3%)
3,209 (15.4%)
3,403 (16.4%)
8,242 (18.6%)
8,597 (19.4%)
14,554 (17.3%)
15,311 (18.2%)
-0.02
DM Medications - Meglitinides; n (%)
243 (1.3%)
216 (1.1%)
373 (1.8%)
360 (1.7%)
688 (1.6%)
693 (1.6%)
1,304 (1.5%)
1,269 (1.5%)
0.00
DM Medications - Metformin; n (%)
12,397 (64.6%)
12,229 (63.7%)
14,006 (67.4%)
13,878 (66.8%)
28,993 (65.3%)
28,918 (65.2%)
55,396 (65.7%)
55,025 (65.2%)
0.01
Concomitant initiation or current use of SGLT2i; n 
(%)
1,051 (5.5%)
1,051 (5.5%)
956 (4.6%)
991 (4.8%)
1,726 (3.9%)
1,657 (3.7%)
3,733 (4.4%)
3,699 (4.4%)
0.00
Concomitant initiation or current use of AGIs; n (%)
63 (0.3%)
67 (0.3%)
49 (0.2%)
48 (0.2%)
176 (0.4%)
171 (0.4%)
288 (0.3%)
286 (0.3%)
0.00
Concomitant initiation or current use of Glitazones; 
n (%)
1,682 (8.8%)
1,642 (8.6%)
2,421 (11.7%)
2,382 (11.5%)
3,540 (8.0%)
3,503 (7.9%)
7,643 (9.1%)
7,527 (8.9%)
0.01
Concomitant initiation or current use of 2nd 
Generation SUs; n (%)
5,856 (30.5%)
5,716 (29.8%)
6,217 (29.9%)
6,177 (29.7%)
14,954 (33.7%)
14,751 (33.2%)
27,027 (32.0%)
26,644 (31.6%)
0.01
Concomitant initiation or current use of Insulin; n 
(%)
1,846 (9.6%)
1,981 (10.3%)
1,893 (9.1%)
2,025 (9.7%)
4,918 (11.1%)
5,173 (11.7%)
8,657 (10.3%)
9,179 (10.9%)
-0.02
Concomitant initiation or current use of 
Meglitinides; n (%)
164 (0.9%)
137 (0.7%)
268 (1.3%)
251 (1.2%)
485 (1.1%)
472 (1.1%)
917 (1.1%)
860 (1.0%)
0.01
Concomitant initiation or current use of Metformin; 
n (%)
10,067 (52.5%)
9,937 (51.8%)
11,259 (54.2%)
11,194 (53.9%)
23,633 (53.3%)
23,628 (53.2%)
44,959 (53.3%)
44,759 (53.1%)
0.00
Past use of SGLT2i  ; n (%)
425 (2.2%)
406 (2.1%)
357 (1.7%)
347 (1.7%)
788 (1.8%)
740 (1.7%)
1,570 (1.9%)
1,493 (1.8%)
0.01
Past use of AGIs ; n (%)
31 (0.2%)
32 (0.2%)
29 (0.1%)
33 (0.2%)
97 (0.2%)
82 (0.2%)
157 (0.2%)
147 (0.2%)
0.00
Past use of Glitazones  ; n (%)
584 (3.0%)
611 (3.2%)
874 (4.2%)
889 (4.3%)
1,242 (2.8%)
1,194 (2.7%)
2,700 (3.2%)
2,694 (3.2%)
0.00
Table 1: Liraglutide vs DPP4i

Past use of 2nd Generation SUs; n (%)
1,529 (8.0%)
1,517 (7.9%)
1,708 (8.2%)
1,699 (8.2%)
3,958 (8.9%)
3,827 (8.6%)
7,195 (8.5%)
7,043 (8.4%)
0.00
Past use of Insulin  ; n (%)
1,257 (6.6%)
1,330 (6.9%)
1,316 (6.3%)
1,378 (6.6%)
3,325 (7.5%)
3,424 (7.7%)
5,898 (7.0%)
6,132 (7.3%)
-0.01
Past use of Meglitinides  ; n (%)
79 (0.4%)
79 (0.4%)
105 (0.5%)
109 (0.5%)
203 (0.5%)
221 (0.5%)
387 (0.5%)
409 (0.5%)
0.00
Past use of metformin (final)  ; n (%)
2,330 (12.1%)
2,292 (11.9%)
2,747 (13.2%)
2,684 (12.9%)
5,360 (12.1%)
5,290 (11.9%)
10,437 (12.4%)
10,266 (12.2%)
0.01
Other Medications
Use of ACE inhibitors; n (%)
8,661 (45.1%)
8,617 (44.9%)
9,287 (44.7%)
9,226 (44.4%)
19,748 (44.5%)
19,720 (44.4%)
37,696 (44.7%)
37,563 (44.5%)
0.00
Use of ARBs; n (%)
6,420 (33.5%)
6,450 (33.6%)
7,474 (36.0%)
7,522 (36.2%)
15,578 (35.1%)
15,693 (35.4%)
29,472 (34.9%)
29,665 (35.2%)
-0.01
Use of Loop Diuretics - United; n (%)
3,398 (17.7%)
3,483 (18.2%)
3,539 (17.0%)
3,497 (16.8%)
9,714 (21.9%)
9,727 (21.9%)
16,651 (19.7%)
16,707 (19.8%)
0.00
Use of other diuretics- United; n (%)
863 (4.5%)
886 (4.6%)
968 (4.7%)
942 (4.5%)
2,181 (4.9%)
2,151 (4.8%)
4,012 (4.8%)
3,979 (4.7%)
0.00
Use of nitrates-United; n (%)
1,373 (7.2%)
1,383 (7.2%)
1,513 (7.3%)
1,556 (7.5%)
3,530 (8.0%)
3,518 (7.9%)
6,416 (7.6%)
6,457 (7.7%)
0.00
Use of other hypertension drugs; n (%)
1,516 (7.9%)
1,494 (7.8%)
1,480 (7.1%)
1,479 (7.1%)
3,871 (8.7%)
3,814 (8.6%)
6,867 (8.1%)
6,787 (8.0%)
0.00
Use of digoxin- United; n (%)
310 (1.6%)
320 (1.7%)
388 (1.9%)
392 (1.9%)
1,018 (2.3%)
1,020 (2.3%)
1,716 (2.0%)
1,732 (2.1%)
-0.01
Use of Anti-arrhythmics; n (%)
345 (1.8%)
337 (1.8%)
339 (1.6%)
355 (1.7%)
954 (2.1%)
969 (2.2%)
1,638 (1.9%)
1,661 (2.0%)
-0.01
Use of COPD/asthma meds- United; n (%)
3,408 (17.8%)
3,324 (17.3%)
3,810 (18.3%)
3,727 (17.9%)
8,701 (19.6%)
8,565 (19.3%)
15,919 (18.9%)
15,616 (18.5%)
0.01
Use of statins; n (%)
13,833 (72.1%)
13,840 (72.1%)
14,918 (71.8%)
14,906 (71.7%)
32,249 (72.7%)
32,353 (72.9%)
61,000 (72.3%)
61,099 (72.4%)
0.00
Use of other lipid-lowering drugs; n (%)
2,758 (14.4%)
2,721 (14.2%)
3,849 (18.5%)
3,863 (18.6%)
6,812 (15.3%)
6,760 (15.2%)
13,419 (15.9%)
13,344 (15.8%)
0.00
Use of antiplatelet agents; n (%)
2,967 (15.5%)
2,944 (15.3%)
4,046 (19.5%)
3,989 (19.2%)
6,933 (15.6%)
6,970 (15.7%)
13,946 (16.5%)
13,903 (16.5%)
0.00
Use of oral anticoagulants (Dabigatran, Rivaroxaban, 
Apixaban, Warfarin); n (%)
1,430 (7.5%)
1,453 (7.6%)
1,380 (6.6%)
1,370 (6.6%)
4,150 (9.4%)
4,252 (9.6%)
6,960 (8.3%)
7,075 (8.4%)
0.00
Use of heparin and other low-molecular weight 
heparins; n (%)
103 (0.5%)
103 (0.5%)
0 (0.0%)
1 (0.0%)
207 (0.5%)
206 (0.5%)
310 (0.4%)
310 (0.4%)
0.00
Use of NSAIDs; n (%)
3,375 (17.6%)
3,404 (17.7%)
3,669 (17.7%)
3,588 (17.3%)
7,998 (18.0%)
7,985 (18.0%)
15,042 (17.8%)
14,977 (17.8%)
0.00
Use of oral corticosteroids; n (%)
3,235 (16.9%)
3,239 (16.9%)
3,346 (16.1%)
3,257 (15.7%)
8,099 (18.2%)
7,995 (18.0%)
14,680 (17.4%)
14,491 (17.2%)
0.01
Use of bisphosphonate (United); n (%)
303 (1.6%)
349 (1.8%)
324 (1.6%)
308 (1.5%)
1,096 (2.5%)
1,047 (2.4%)
1,723 (2.0%)
1,704 (2.0%)
0.00
Use of opioids- United; n (%)
5,625 (29.3%)
5,525 (28.8%)
6,002 (28.9%)
6,018 (29.0%)
13,107 (29.5%)
13,033 (29.4%)
24,734 (29.3%)
24,576 (29.1%)
0.00
Use of antidepressants; n (%)
6,011 (31.3%)
5,924 (30.9%)
6,205 (29.9%)
6,074 (29.2%)
14,221 (32.0%)
14,173 (31.9%)
26,437 (31.3%)
26,171 (31.0%)
0.01
Use of antipsychotics; n (%)
460 (2.4%)
443 (2.3%)
366 (1.8%)
365 (1.8%)
1,104 (2.5%)
1,044 (2.4%)
1,930 (2.3%)
1,852 (2.2%)
0.01
Use of anticonvulsants; n (%)
4,060 (21.2%)
3,973 (20.7%)
3,106 (14.9%)
3,129 (15.1%)
8,847 (19.9%)
8,786 (19.8%)
16,013 (19.0%)
15,888 (18.8%)
0.01
Use of lithium- United; n (%)
24 (0.1%)
22 (0.1%)
37 (0.2%)
27 (0.1%)
66 (0.1%)
55 (0.1%)
127 (0.2%)
104 (0.1%)
0.03
Use of Benzos- United; n (%)
2,251 (11.7%)
2,238 (11.7%)
2,514 (12.1%)
2,553 (12.3%)
4,924 (11.1%)
4,945 (11.1%)
9,689 (11.5%)
9,736 (11.5%)
0.00
Use of anxiolytics/hypnotics- United; n (%)
1,429 (7.4%)
1,386 (7.2%)
1,747 (8.4%)
1,702 (8.2%)
3,365 (7.6%)
3,365 (7.6%)
6,541 (7.8%)
6,453 (7.7%)
0.00
Use of dementia meds- United; n (%)
186 (1.0%)
205 (1.1%)
153 (0.7%)
146 (0.7%)
895 (2.0%)
917 (2.1%)
1,234 (1.5%)
1,268 (1.5%)
0.00
Use of antiparkinsonian meds- United; n (%)
664 (3.5%)
666 (3.5%)
630 (3.0%)
638 (3.1%)
1,810 (4.1%)
1,794 (4.0%)
3,104 (3.7%)
3,098 (3.7%)
0.00
Any use of pramlintide; n (%)
2 (0.0%)
5 (0.0%)
8 (0.0%)
25 (0.1%)
**
**
**
**
**
**
Any use of 1st generation sulfonylureas; n (%)
4 (0.0%)
0 (0.0%)
1 (0.0%)
1 (0.0%)
**
**
**
**
**
**
Entresto (sacubitril/valsartan); n (%)
50 (0.3%)
47 (0.2%)
18 (0.1%)
13 (0.1%)
44 (0.1%)
27 (0.1%)
112 (0.1%)
087 (0.1%)
0.00
Initiation as monotherapy  ; n (%)
1,829 (9.5%)
0 (0.0%)
1,585 (7.6%)
0 (0.0%)
3,010 (6.8%)
0 (0.0%)
6,424 (7.6%)
#VALUE!
#VALUE!
Labs
                                          39,964                                           39,964 
Lab values- HbA1c (%) ; n (%)
7,630 (39.8%)
7,216 (37.6%)
1,331 (6.4%)
1,167 (5.6%)
N/A
N/A
8,961 (22.4%)
8,383 (21.0%)
0.03
Lab values- HbA1c (%) (within 3 months) ; n (%)
6,032 (31.4%)
5,538 (28.9%)
1,052 (5.1%)
916 (4.4%)
N/A
N/A
7,084 (17.7%)
6,454 (16.1%)
0.04
Lab values- HbA1c (%) (within 6 months) ; n (%)
7,630 (39.8%)
7,216 (37.6%)
1,331 (6.4%)
1,167 (5.6%)
N/A
N/A
8,961 (22.4%)
8,383 (21.0%)
0.03
Lab values- BNP; n (%)
211 (1.1%)
206 (1.1%)
25 (0.1%)
34 (0.2%)
N/A
N/A
236 (0.6%)
240 (0.6%)
0.00
Lab values- BNP (within 3 months); n (%)
117 (0.6%)
121 (0.6%)
14 (0.1%)
28 (0.1%)
N/A
N/A
131 (0.3%)
149 (0.4%)
-0.02
Lab values- BNP (within 6 months); n (%)
211 (1.1%)
206 (1.1%)
25 (0.1%)
34 (0.2%)
N/A
N/A
236 (0.6%)
240 (0.6%)
0.00
Lab values- BUN (mg/dl); n (%)
7,901 (41.2%)
7,376 (38.4%)
1,341 (6.5%)
1,179 (5.7%)
N/A
N/A
9,242 (23.1%)
8,555 (21.4%)
0.04
Lab values- BUN (mg/dl) (within 3 months); n (%)
6,155 (32.1%)
5,577 (29.1%)
1,038 (5.0%)
901 (4.3%)
N/A
N/A
7,193 (18.0%)
6,478 (16.2%)
0.05
Lab values- BUN (mg/dl) (within 6 months); n (%)
7,901 (41.2%)
7,376 (38.4%)
1,341 (6.5%)
1,179 (5.7%)
N/A
N/A
9,242 (23.1%)
8,555 (21.4%)
0.04
Lab values- Creatinine (mg/dl) ; n (%)
8,092 (42.2%)
7,583 (39.5%)
1,405 (6.8%)
1,228 (5.9%)
N/A
N/A
9,497 (23.8%)
8,811 (22.0%)
0.04
Lab values- Creatinine (mg/dl) (within 3 months) ; n 
(%)
6,325 (33.0%)
5,734 (29.9%)
1,089 (5.2%)
933 (4.5%)
N/A
N/A
7,414 (18.6%)
6,667 (16.7%)
0.05
Lab values- Creatinine (mg/dl) (within 6 months) ; n 
(%)
8,092 (42.2%)
7,583 (39.5%)
1,405 (6.8%)
1,228 (5.9%)
N/A
N/A
9,497 (23.8%)
8,811 (22.0%)
0.04
Lab values- HDL level (mg/dl); n (%)
6,566 (34.2%)
6,095 (31.8%)
1,190 (5.7%)
1,025 (4.9%)
N/A
N/A
7,756 (19.4%)
7,120 (17.8%)
0.04
Lab values- HDL level (mg/dl) (within 3 months); n (%)
4,811 (25.1%)
4,342 (22.6%)
876 (4.2%)
751 (3.6%)
N/A
N/A
5,687 (14.2%)
5,093 (12.7%)
0.04
Lab values- HDL level (mg/dl) (within 6 months); n (%)
6,566 (34.2%)
6,095 (31.8%)
1,190 (5.7%)
1,025 (4.9%)
N/A
N/A
7,756 (19.4%)
7,120 (17.8%)
0.04
Lab values- LDL level (mg/dl) ; n (%)
6,757 (35.2%)
6,299 (32.8%)
1,235 (5.9%)
1,085 (5.2%)
N/A
N/A
7,992 (20.0%)
7,384 (18.5%)
0.04
Lab values- LDL level (mg/dl) (within 3 months) ; n (%)
4,956 (25.8%)
4,495 (23.4%)
911 (4.4%)
789 (3.8%)
N/A
N/A
5,867 (14.7%)
5,284 (13.2%)
0.04
Lab values- LDL level (mg/dl) (within 6 months) ; n (%)
6,757 (35.2%)
6,299 (32.8%)
1,235 (5.9%)
1,085 (5.2%)
N/A
N/A
7,992 (20.0%)
7,384 (18.5%)
0.04
Lab values- NT-proBNP; n (%)
36 (0.2%)
35 (0.2%)
3 (0.0%)
2 (0.0%)
N/A
N/A
39 (0.1%)
0 (0.1%)
-
Lab values- NT-proBNP (within 3 months); n (%)
21 (0.1%)
22 (0.1%)
3 (0.0%)
0 (0.0%)
N/A
N/A
24 (0.1%)
0 (0.1%)
-
Lab values- NT-proBNP (within 6 months); n (%)
36 (0.2%)
35 (0.2%)
3 (0.0%)
2 (0.0%)
N/A
N/A
39 (0.1%)
37 (0.1%)
-
Lab values- Total cholesterol (mg/dl) ; n (%)
6,680 (34.8%)
6,217 (32.4%)
1,209 (5.8%)
1,039 (5.0%)
N/A
N/A
7,889 (19.7%)
7,256 (18.2%)
0.04
Lab values- Total cholesterol (mg/dl) (within 3 
months) ; n (%)
4,901 (25.5%)
4,436 (23.1%)
892 (4.3%)
761 (3.7%)
N/A
N/A
5,793 (14.5%)
5,197 (13.0%)
0.04
Lab values- Total cholesterol (mg/dl) (within 6 
months) ; n (%)
6,680 (34.8%)
6,217 (32.4%)
1,209 (5.8%)
1,039 (5.0%)
N/A
N/A
7,889 (19.7%)
7,256 (18.2%)
0.04
Lab values- Triglyceride level (mg/dl); n (%)
6,635 (34.6%)
6,161 (32.1%)
1,197 (5.8%)
1,020 (4.9%)
N/A
N/A
7,832 (19.6%)
7,181 (18.0%)
0.04
Lab values- Triglyceride level (mg/dl) (within 3 
months); n (%)
4,872 (25.4%)
4,399 (22.9%)
885 (4.3%)
747 (3.6%)
N/A
N/A
5,757 (14.4%)
5,146 (12.9%)
0.04
Lab values- Triglyceride level (mg/dl) (within 6 
months); n (%)
6,635 (34.6%)
6,161 (32.1%)
1,197 (5.8%)
1,020 (4.9%)
N/A
N/A
7,832 (19.6%)
7,181 (18.0%)
0.04
Lab result number- HbA1c (%) mean (only 2 to 20 
included) 
7,607
                                            
7,179
                                            
1,263
                                            
1,104
                                            
N/A
N/A
                                             8,870                                              8,283 
...mean (sd)
8.05 (1.64)
8.03 (1.73)
0.01
8.02 (1.62)
8.03 (1.74)
-0.01
N/A
N/A
#VALUE!
8.05 (1.64)
8.03 (1.73)
0.01
...median [IQR]
7.70 [6.95, 8.80]
7.70 [6.80, 8.93]
0.00
7.70 [6.90, 8.80]
7.70 [6.80, 8.94]
0.00
N/A
N/A
#VALUE!
7.70 (1.64)
7.70 (1.73)
0.00
...Missing; n (%)
11,580 (60.4%)
12,008 (62.6%)
-0.05
19,514 (93.9%)
19,673 (94.7%)
-0.03
N/A
N/A
#VALUE!
31,094 (77.8%)
31,681 (79.3%)
-0.04
Table 1: Liraglutide vs DPP4i

Lab result number- BNP mean 
211
                                                
206
                                                
25
                                                   
34
                                                   
N/A
N/A
                                                 236                                                  240 
...mean (sd)
178.05 (453.45)
112.46 (210.39)
0.19
11,349.77 (55,969.06)
98.46 (169.53)
0.28
N/A
N/A
#VALUE!
1361.49 (17968.03)
110.48 (205.64)
0.10
...median [IQR]
79.90 [31.80, 158.50]
44.20 [21.62, 112.70]
0.10
72.00 [34.50, 293.25]
44.35 [16.25, 119.12]
0.00
N/A
N/A
#VALUE!
#VALUE!
#VALUE!
#VALUE!
...Missing; n (%)
18,976 (98.9%)
18,981 (98.9%)
0.00
20,752 (99.9%)
20,743 (99.8%)
0.03
N/A
N/A
#VALUE!
39,728 (99.4%)
39,724 (99.4%)
0.00
Lab result number- BUN (mg/dl) mean 
                                             7,901                                              7,376 
                                             1,341                                              1,179 
N/A
N/A
                                             9,242                                              8,555 
...mean (sd)
19.20 (8.24)
19.56 (8.24)
-0.04
424.78 (7,460.56)
689.04 (11,932.92)
-0.03
N/A
N/A
#VALUE!
78.05 (2841.27)
111.82 (4428.80)
-0.01
...median [IQR]
17.40 [14.00, 22.00]
18.00 [14.00, 23.00]
-0.07
17.00 [13.37, 21.00]
18.00 [14.25, 22.00]
0.00
N/A
N/A
#VALUE!
#VALUE!
#VALUE!
#VALUE!
...Missing; n (%)
11,286 (58.8%)
11,811 (61.6%)
-0.06
19,436 (93.5%)
19,598 (94.3%)
-0.03
N/A
N/A
#VALUE!
30,722 (76.9%)
31,409 (78.6%)
-0.04
Lab result number- Creatinine (mg/dl) mean (only 0.1 
to 15 included) 
                                             8,029                                              7,538 
                                             1,288                                              1,121 
N/A
N/A
                                             9,317                                              8,659 
...mean (sd)
1.06 (0.41)
1.04 (0.37)
0.05
1.02 (0.38)
1.01 (0.32)
0.03
N/A
N/A
#VALUE!
1.05 (0.41)
1.04 (0.36)
0.03
...median [IQR]
0.97 [0.80, 1.21]
0.96 [0.80, 1.20]
0.03
0.96 [0.79, 1.12]
0.96 [0.80, 1.14]
0.00
N/A
N/A
#VALUE!
0.97 (0.41)
0.96 (0.36)
0.03
...Missing; n (%)
11,158 (58.2%)
11,649 (60.7%)
-0.05
19,489 (93.8%)
19,656 (94.6%)
-0.03
N/A
N/A
#VALUE!
30,647 (76.7%)
31,305 (78.3%)
-0.04
Lab result number- HDL level (mg/dl) mean (only 
=<5000 included) 
                                             6,566                                              6,095 
                                             1,186                                              1,021 
N/A
N/A
                                             7,752                                              7,116 
...mean (sd)
46.32 (13.75)
45.91 (13.13)
0.03
45.33 (15.96)
44.46 (13.85)
0.06
N/A
N/A
#VALUE!
46.17 (14.11)
45.70 (13.24)
0.03
...median [IQR]
44.00 [37.00, 53.50]
44.00 [37.00, 53.00]
0.00
44.00 [36.00, 53.00]
43.00 [36.00, 52.00]
0.07
N/A
N/A
#VALUE!
44.00 (14.11)
43.86 (13.24)
0.01
...Missing; n (%)
12,621 (65.8%)
13,092 (68.2%)
-0.05
19,591 (94.3%)
19,756 (95.1%)
-0.04
N/A
N/A
#VALUE!
32,212 (80.6%)
32,848 (82.2%)
-0.04
Lab result number- LDL level (mg/dl) mean (only 
=<5000 included) 
                                             6,629                                              6,170 
                                             1,149                                                  949 
N/A
N/A
                                             7,778                                              7,119 
...mean (sd)
85.21 (38.16)
81.93 (36.98)
0.09
84.96 (41.84)
83.77 (40.06)
0.03
N/A
N/A
#VALUE!
85.17 (38.73)
82.18 (37.41)
0.08
...median [IQR]
82.00 [62.00, 106.50]
79.00 [60.00, 102.00]
0.08
84.00 [61.50, 108.00]
84.00 [62.00, 106.00]
0.00
N/A
N/A
#VALUE!
82.30 (38.73)
79.67 (37.41)
0.07
...Missing; n (%)
12,558 (65.5%)
13,017 (67.8%)
-0.05
19,628 (94.5%)
19,828 (95.4%)
-0.04
N/A
N/A
#VALUE!
32,186 (80.5%)
32,845 (82.2%)
-0.04
Lab result number- Total cholesterol (mg/dl) mean 
(only =<5000 included) 
                                             6,675                                              6,213 
                                             1,205                                              1,034 
N/A
N/A
                                             7,880                                              7,247 
...mean (sd)
170.81 (45.37)
167.71 (42.55)
0.07
171.98 (53.53)
170.54 (48.18)
0.03
N/A
N/A
#VALUE!
170.99 (46.71)
168.11 (43.40)
0.06
...median [IQR]
164.67 [141.00, 195.00]
162.00 [139.00, 191.00]
0.06
167.00 [142.00, 199.50]
166.00 [142.88, 196.00]
0.02
N/A
N/A
#VALUE!
165.03 (46.71)
162.57 (43.40)
0.05
...Missing; n (%)
12,512 (65.2%)
12,974 (67.6%)
-0.05
19,572 (94.2%)
19,743 (95.0%)
-0.04
N/A
N/A
#VALUE!
32,084 (80.3%)
32,717 (81.9%)
-0.04
Lab result number- Triglyceride level (mg/dl) mean 
(only =<5000 included) 
                                             6,634                                              6,161 
                                             1,193                                              1,016 
N/A
N/A
                                             7,827                                              7,177 
...mean (sd)
183.24 (145.11)
184.97 (135.08)
-0.01
188.33 (172.01)
187.81 (148.81)
0.00
N/A
N/A
#VALUE!
184.02 (149.53)
185.37 (137.12)
-0.01
...median [IQR]
152.00 [109.00, 217.00]
155.00 [112.00, 218.00]
-0.02
149.00 [103.00, 221.25]
155.00 [109.00, 221.00]
-0.04
N/A
N/A
#VALUE!
151.54 (149.53)
155.00 (137.12)
-0.02
...Missing; n (%)
12,553 (65.4%)
13,026 (67.9%)
-0.05
19,584 (94.3%)
19,761 (95.1%)
-0.04
N/A
N/A
#VALUE!
32,137 (80.4%)
32,787 (82.0%)
-0.04
Lab result number- Hemoglobin mean (only >0 
included)
                                             5,571                                              5,078 
                                                 891                                                  783 
N/A
N/A
                                             6,462                                              5,861 
...mean (sd)
13.38 (1.69)
13.43 (1.61)
-0.03
6,166.82 (167,694.97)
13.30 (2.42)
0.05
N/A
N/A
#VALUE!
861.83 (62249.00)
13.41 (1.74)
0.02
...median [IQR]
13.40 [12.30, 14.50]
13.40 [12.40, 14.50]
0.00
13.30 [12.40, 14.45]
13.45 [12.40, 14.70]
0.00
N/A
N/A
#VALUE!
#VALUE!
13.41 (1.74)
#VALUE!
...Missing; n (%)
13,616 (71.0%)
14,109 (73.5%)
-0.06
19,886 (95.7%)
19,994 (96.2%)
-0.03
N/A
N/A
#VALUE!
33,502 (83.8%)
34,103 (85.3%)
-0.04
Lab result number- Serum sodium mean (only > 90 
and < 190 included)
                                             7,873                                              7,386 
                                             1,270                                              1,096 
N/A
N/A
                                             9,143                                              8,482 
...mean (sd)
139.61 (2.73)
139.62 (2.63)
0.00
139.31 (2.56)
139.07 (2.53)
0.09
N/A
N/A
#VALUE!
139.57 (2.71)
139.55 (2.62)
0.01
...median [IQR]
140.00 [138.00, 141.50]
140.00 [138.00, 141.33]
0.00
139.12 [138.00, 141.00]
139.00 [137.54, 141.00]
0.05
N/A
N/A
#VALUE!
139.88 (2.71)
139.87 (2.62)
0.00
...Missing; n (%)
11,314 (59.0%)
11,801 (61.5%)
-0.05
19,507 (93.9%)
19,681 (94.7%)
-0.03
N/A
N/A
#VALUE!
30,821 (77.1%)
31,482 (78.8%)
-0.04
Lab result number- Albumin mean (only >0 and <=10 
included)
                                             7,378                                              6,868 
                                             1,142                                              1,023 
N/A
N/A
                                             8,520                                              7,891 
...mean (sd)
4.23 (0.32)
4.22 (0.31)
0.03
4.11 (0.72)
4.11 (0.68)
0.00
N/A
N/A
#VALUE!
4.21 (0.40)
4.21 (0.38)
0.00
...median [IQR]
4.25 [4.00, 4.45]
4.20 [4.00, 4.40]
0.16
4.20 [4.00, 4.40]
4.20 [4.00, 4.40]
0.00
N/A
N/A
#VALUE!
4.24 (0.40)
4.20 (0.38)
0.10
...Missing; n (%)
11,809 (61.5%)
12,319 (64.2%)
-0.06
19,635 (94.5%)
19,754 (95.1%)
-0.03
N/A
N/A
#VALUE!
31,444 (78.7%)
32,073 (80.3%)
-0.04
Lab result number- Glucose (fasting or random) mean 
(only 10-1000 included)
                                             7,859                                              7,362 
                                             1,261                                              1,078 
N/A
N/A
                                             9,120                                              8,440 
...mean (sd)
168.28 (66.76)
166.71 (68.39)
0.02
164.30 (62.49)
168.11 (68.55)
-0.06
N/A
N/A
#VALUE!
167.73 (66.19)
166.89 (68.41)
0.01
...median [IQR]
153.00 [124.00, 196.00]
151.00 [119.00, 196.00]
0.03
150.00 [121.00, 193.00]
152.00 [119.00, 197.62]
-0.03
N/A
N/A
#VALUE!
152.59 (66.19)
151.13 (68.41)
0.02
...Missing; n (%)
11,328 (59.0%)
11,825 (61.6%)
-0.05
19,516 (93.9%)
19,699 (94.8%)
-0.04
N/A
N/A
#VALUE!
30,844 (77.2%)
31,524 (78.9%)
-0.04
Lab result number- Potassium mean (only 1-7 
included)
                                             8,018                                              7,536 
                                             1,296                                              1,146 
N/A
N/A
                                             9,314                                              8,682 
...mean (sd)
4.45 (0.44)
4.46 (0.43)
-0.02
4.34 (0.45)
4.36 (0.45)
-0.04
N/A
N/A
#VALUE!
4.43 (0.44)
4.45 (0.43)
-0.05
...median [IQR]
4.45 [4.20, 4.70]
4.45 [4.20, 4.70]
0.00
4.35 [4.00, 4.60]
4.35 [4.00, 4.60]
0.00
N/A
N/A
#VALUE!
4.44 (0.44)
4.44 (0.43)
0.00
...Missing; n (%)
11,169 (58.2%)
11,651 (60.7%)
-0.05
19,481 (93.8%)
19,631 (94.5%)
-0.03
N/A
N/A
#VALUE!
30,650 (76.7%)
31,282 (78.3%)
-0.04
Comorbidity Scores
CCI (180 days)- ICD9 and ICD10 
...mean (sd)
2.81 (1.90)
2.81 (1.88)
0.00
2.11 (1.53)
2.10 (1.54)
0.01
2.88 (2.01)
2.88 (1.99)
0.00
2.67 (1.88)
2.67 (1.86)
0.00
...median [IQR]
2.00 [1.00, 4.00]
2.00 [1.00, 4.00]
0.00
2.00 [1.00, 3.00]
2.00 [1.00, 3.00]
0.00
2.00 [1.00, 4.00]
2.00 [1.00, 4.00]
0.00
2.00 (1.88)
2.00 (1.86)
0.00
Frailty Score: Qualitative Version 365 days as 
Categories, v1
...0; n (%)
9,675 (50.4%)
9,627 (50.2%)
0.00
6,331 (30.5%)
6,391 (30.8%)
-0.93
14,745 (33.2%)
14,927 (33.6%)
-0.01
30,751 (36.5%)
30,945 (36.7%)
0.00
...1 to 2; n (%)
6,091 (31.7%)
6,185 (32.2%)
-0.01
9,099 (43.8%)
9,298 (44.8%)
-1.25
15,032 (33.9%)
15,014 (33.8%)
0.00
30,222 (35.8%)
30,497 (36.2%)
-0.01
...3 or more; n (%)
3,421 (17.8%)
3,375 (17.6%)
0.01
5,347 (25.7%)
5,088 (24.5%)
0.03
14,604 (32.9%)
14,440 (32.5%)
0.01
23,372 (27.7%)
22,903 (27.2%)
0.01
Frailty Score: Empirical Version 365 days as 
Categories, 
...< 0.12908; n (%)
3,587 (18.7%)
3,404 (17.7%)
0.03
3,596 (17.3%)
3,485 (16.8%)
0.01
4,452 (10.0%)
4,046 (9.1%)
0.03
11,635 (13.8%)
10,935 (13.0%)
0.02
...0.12908 - 0.1631167; n (%)
6,091 (31.7%)
6,047 (31.5%)
0.00
6,834 (32.9%)
6,788 (32.7%)
0.00
10,566 (23.8%)
10,686 (24.1%)
-0.01
23,491 (27.9%)
23,521 (27.9%)
0.00
...>= 0.1631167; n (%)
9,509 (49.6%)
9,736 (50.7%)
-0.02
10,347 (49.8%)
10,504 (50.6%)
-0.02
29,363 (66.2%)
29,649 (66.8%)
-0.01
49,219 (58.4%)
49,889 (59.1%)
-0.01
Non-Frailty; n (%)
11,603 (60.5%)
11,864 (61.8%)
-0.03
11,804 (56.8%)
11,670 (56.2%)
0.01
1,841 (4.1%)
1,879 (4.2%)
-0.01
25,248 (29.9%)
25,413 (30.1%)
0.00
Frailty Score (mean): Qualitative Version 365 days, v1
...mean (sd)
1.22 (1.81)
1.19 (1.72)
0.02
1.69 (1.76)
1.64 (1.71)
0.03
1.99 (2.19)
1.96 (2.16)
0.01
1.74 (2.01)
1.71 (1.96)
0.02
...median [IQR]
0.00 [0.00, 2.00]
0.00 [0.00, 2.00]
0.00
1.00 [0.00, 3.00]
1.00 [0.00, 2.00]
0.00
1.00 [0.00, 3.00]
1.00 [0.00, 3.00]
0.00
0.77 (2.01)
0.77 (1.96)
0.00
Frailty Score (mean): Empirical Version 365 days, 
...mean (sd)
0.17 (0.06)
0.17 (0.05)
0.00
0.17 (0.05)
0.17 (0.05)
0.00
0.20 (0.06)
0.20 (0.06)
0.00
0.19 (0.06)
0.19 (0.06)
0.00
...median [IQR]
0.16 [0.14, 0.20]
0.16 [0.14, 0.20]
0.00
0.16 [0.13, 0.19]
0.16 [0.13, 0.19]
0.00
0.18 [0.15, 0.23]
0.18 [0.15, 0.23]
0.00
0.17 (0.06)
0.17 (0.06)
0.00
Table 1: Liraglutide vs DPP4i

Healthcare Utilization
Any hospitalization; n (%)
1,541 (8.0%)
1,546 (8.1%)
1,803 (8.7%)
1,753 (8.4%)
3,978 (9.0%)
3,932 (8.9%)
7,322 (8.7%)
7,231 (8.6%)
0.00
Any hospitalization within prior 30 days; n (%)
297 (1.5%)
323 (1.7%)
336 (1.6%)
314 (1.5%)
799 (1.8%)
769 (1.7%)
1,432 (1.7%)
1,406 (1.7%)
0.00
Any hospitalization during prior 31-180 days; n (%)
1,301 (6.8%)
1,288 (6.7%)
1,511 (7.3%)
1,494 (7.2%)
3,337 (7.5%)
3,308 (7.5%)
6,149 (7.3%)
6,090 (7.2%)
0.00
Endocrinologist Visit; n (%)
3,589 (18.7%)
3,976 (20.7%)
4,157 (20.0%)
4,563 (22.0%)
9,939 (22.4%)
10,730 (24.2%)
17,685 (21.0%)
19,269 (22.8%)
-0.04
Endocrinologist Visit (30 days prior); n (%)
2,456 (12.8%)
2,552 (13.3%)
2,994 (14.4%)
3,142 (15.1%)
6,564 (14.8%)
6,748 (15.2%)
12,014 (14.2%)
12,442 (14.8%)
-0.02
Endocrinologist Visit (31 to 180 days prior); n (%)
2,705 (14.1%)
2,807 (14.6%)
3,031 (14.6%)
3,169 (15.3%)
7,860 (17.7%)
8,000 (18.0%)
13,596 (16.1%)
13,976 (16.6%)
-0.01
Internal medicine/family medicine visits; n (%)
16,005 (83.4%)
16,049 (83.6%)
17,889 (86.1%)
17,817 (85.8%)
37,186 (83.8%)
37,213 (83.8%)
71,080 (84.3%)
71,079 (84.3%)
0.00
Internal medicine/family medicine visits (30 days 
prior) ; n (%)
11,488 (59.9%)
11,453 (59.7%)
12,820 (61.7%)
12,747 (61.4%)
25,129 (56.6%)
25,010 (56.4%)
49,437 (58.6%)
49,210 (58.3%)
0.01
Internal medicine/family medicine visits (31 to 180 
days prior) ; n (%)
14,693 (76.6%)
14,746 (76.9%)
16,264 (78.3%)
16,214 (78.0%)
34,222 (77.1%)
34,115 (76.9%)
65,179 (77.3%)
65,075 (77.2%)
0.00
Cardiologist visit; n (%)
6,554 (34.2%)
6,623 (34.5%)
6,991 (33.6%)
6,941 (33.4%)
16,101 (36.3%)
16,090 (36.3%)
29,646 (35.1%)
29,654 (35.2%)
0.00
Number of Cardiologist visits (30 days prior); n (%)
2,161 (11.3%)
2,239 (11.7%)
2,407 (11.6%)
2,317 (11.2%)
5,233 (11.8%)
5,130 (11.6%)
9,801 (11.6%)
9,686 (11.5%)
0.00
Number of Cardiologist visits (31 to 180 days prior); 
n (%)
5,709 (29.8%)
5,679 (29.6%)
5,994 (28.8%)
5,953 (28.7%)
14,170 (31.9%)
14,138 (31.9%)
25,873 (30.7%)
25,770 (30.6%)
0.00
Electrocardiogram ; n (%)
6,660 (34.7%)
6,494 (33.8%)
7,436 (35.8%)
7,460 (35.9%)
15,567 (35.1%)
15,619 (35.2%)
29,663 (35.2%)
29,573 (35.1%)
0.00
Use of glucose test strips; n (%)
745 (3.9%)
797 (4.2%)
984 (4.7%)
992 (4.8%)
1,670 (3.8%)
1,709 (3.9%)
3,399 (4.0%)
3,498 (4.1%)
-0.01
Dialysis; n (%)
7 (0.0%)
11 (0.1%)
5 (0.0%)
9 (0.0%)
30 (0.1%)
18 (0.0%)
042 (0.0%)
038 (0.0%)
#DIV/0!
Naive new user v8 ; n (%)
2,841 (14.8%)
2,939 (15.3%)
2,502 (12.0%)
2,584 (12.4%)
4,759 (10.7%)
4,824 (10.9%)
10,102 (12.0%)
10,347 (12.3%)
-0.01
N antidiabetic drugs at index date  
...mean (sd)
2.08 (0.83)
2.07 (0.88)
0.01
2.11 (0.84)
2.10 (0.90)
0.01
2.12 (0.82)
2.11 (0.85)
0.01
2.11 (0.83)
2.10 (0.87)
0.01
...median [IQR]
2.00 [1.00, 3.00]
2.00 [1.00, 3.00]
0.00
2.00 [2.00, 3.00]
2.00 [1.00, 3.00]
0.00
2.00 [2.00, 3.00]
2.00 [1.00, 3.00]
0.00
2.00 (0.83)
2.00 (0.87)
0.00
number of different/distinct medication 
prescriptions
...mean (sd)
11.67 (5.48)
11.62 (5.07)
0.01
11.57 (5.27)
11.49 (4.84)
0.02
11.32 (5.10)
11.28 (4.68)
0.01
11.46 (5.23)
11.41 (4.81)
0.01
...median [IQR]
11.00 [8.00, 15.00]
11.00 [8.00, 14.00]
0.00
11.00 [8.00, 14.00]
11.00 [8.00, 14.00]
0.00
11.00 [8.00, 14.00]
11.00 [8.00, 14.00]
0.00
11.00 (5.23)
11.00 (4.81)
0.00
Number of Hospitalizations
...mean (sd)
0.10 (0.36)
0.10 (0.36)
0.00
0.10 (0.35)
0.10 (0.35)
0.00
0.11 (0.40)
0.11 (0.40)
0.00
0.11 (0.38)
0.11 (0.38)
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, 0.00]
0.00
0.00 (0.38)
0.00 (0.38)
0.00
Number of hospital days
...mean (sd)
0.50 (2.40)
0.49 (2.58)
0.00
0.47 (2.10)
0.46 (2.30)
0.00
0.64 (2.82)
0.63 (2.98)
0.00
0.57 (2.57)
0.56 (2.74)
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, 0.00]
0.00
0.00 (2.57)
0.00 (2.74)
0.00
Number of Emergency Department (ED) visits 
...mean (sd)
0.42 (1.17)
0.41 (1.20)
0.01
0.15 (1.58)
0.16 (1.22)
-0.01
0.46 (1.22)
0.45 (1.22)
0.01
0.37 (1.31)
0.37 (1.22)
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, 0.00]
0.00
0.00 (1.31)
0.00 (1.22)
0.00
Number of Office visits
...mean (sd)
5.85 (4.25)
5.79 (4.09)
0.01
6.06 (4.48)
6.03 (4.28)
0.01
6.48 (4.81)
6.44 (4.59)
0.01
6.23 (4.61)
6.19 (4.40)
0.01
...median [IQR]
5.00 [3.00, 8.00]
5.00 [3.00, 8.00]
0.00
5.00 [3.00, 8.00]
5.00 [3.00, 8.00]
0.00
5.00 [3.00, 9.00]
5.00 [3.00, 8.00]
0.00
5.00 (4.61)
5.00 (4.40)
0.00
Number of Endocrinologist visits
...mean (sd)
0.94 (3.12)
1.08 (3.57)
-0.04
1.02 (3.36)
1.15 (3.67)
-0.04
1.37 (4.44)
1.59 (5.06)
-0.05
1.19 (3.92)
1.37 (4.44)
-0.04
...median [IQR]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00
0.00 (3.92)
0.00 (4.44)
0.00
Number of internal medicine/family medicine visits
...mean (sd)
10.22 (14.26)
10.41 (14.28)
-0.01
7.58 (9.28)
7.78 (9.68)
-0.02
8.74 (11.41)
8.76 (11.44)
0.00
8.79 (11.66)
8.89 (11.76)
-0.01
...median [IQR]
6.00 [2.00, 13.00]
6.00 [2.00, 13.00]
0.00
5.00 [2.00, 10.00]
5.00 [2.00, 10.00]
0.00
5.00 [2.00, 12.00]
5.00 [2.00, 12.00]
0.00
5.23 (11.66)
5.23 (11.76)
0.00
Number of Cardiologist visits
...mean (sd)
1.73 (4.10)
1.70 (4.02)
0.01
1.54 (3.79)
1.53 (3.73)
0.00
1.97 (4.77)
1.97 (4.91)
0.00
1.81 (4.40)
1.80 (4.45)
0.00
...median [IQR]
0.00 [0.00, 2.00]
0.00 [0.00, 2.00]
0.00
0.00 [0.00, 2.00]
0.00 [0.00, 2.00]
0.00
0.00 [0.00, 2.00]
0.00 [0.00, 2.00]
0.00
0.00 (4.40)
0.00 (4.45)
0.00
Number electrocardiograms received 
...mean (sd)
0.67 (1.37)
0.67 (1.47)
0.00
0.63 (1.19)
0.64 (1.21)
-0.01
0.70 (1.37)
0.70 (1.34)
0.00
0.68 (1.33)
0.68 (1.34)
0.00
...median [IQR]
0.00 [0.00, 1.00]
0.00 [0.00, 1.00]
0.00
0.00 [0.00, 1.00]
0.00 [0.00, 1.00]
0.00
0.00 [0.00, 1.00]
0.00 [0.00, 1.00]
0.00
0.00 (1.33)
0.00 (1.34)
0.00
Number of HbA1c tests ordered
...mean (sd)
1.39 (0.93)
1.39 (0.92)
0.00
1.14 (0.94)
1.15 (0.95)
-0.01
1.52 (0.87)
1.52 (0.88)
0.00
1.40 (0.90)
1.40 (0.91)
0.00
...median [IQR]
1.00 [1.00, 2.00]
1.00 [1.00, 2.00]
0.00
1.00 [0.00, 2.00]
1.00 [0.00, 2.00]
0.00
1.00 [1.00, 2.00]
1.00 [1.00, 2.00]
0.00
1.00 (0.90)
1.00 (0.91)
0.00
Number of glucose tests ordered
...mean (sd)
0.54 (1.37)
0.57 (1.40)
-0.02
0.50 (1.31)
0.50 (1.20)
0.00
0.50 (1.09)
0.51 (1.13)
-0.01
0.51 (1.21)
0.52 (1.21)
-0.01
...median [IQR]
0.00 [0.00, 0.00]
0.00 [0.00, 1.00]
0.00
0.00 [0.00, 1.00]
0.00 [0.00, 1.00]
0.00
0.00 [0.00, 1.00]
0.00 [0.00, 1.00]
0.00
0.00 (1.21)
0.00 (1.21)
0.00
Number of lipid tests ordered
...mean (sd)
1.09 (0.99)
1.08 (1.01)
0.01
1.00 (1.33)
1.00 (1.30)
0.00
1.11 (0.85)
1.10 (0.88)
0.01
1.08 (1.02)
1.07 (1.03)
0.01
...median [IQR]
1.00 [0.00, 2.00]
1.00 [0.00, 2.00]
0.00
1.00 [0.00, 1.00]
1.00 [0.00, 1.00]
0.00
1.00 [1.00, 2.00]
1.00 [1.00, 2.00]
0.00
1.00 (1.02)
1.00 (1.03)
0.00
Number of creatinine tests ordered
...mean (sd)
0.05 (0.30)
0.06 (0.30)
-0.03
0.06 (0.36)
0.06 (0.34)
0.00
0.09 (0.39)
0.10 (0.41)
-0.02
0.07 (0.36)
0.08 (0.37)
-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, 0.00]
0.00
0.00 (0.36)
0.00 (0.37)
0.00
Number of BUN tests ordered
...mean (sd)
0.03 (0.23)
0.03 (0.23)
0.00
0.04 (0.27)
0.04 (0.27)
0.00
0.06 (0.30)
0.06 (0.32)
0.00
0.05 (0.28)
0.05 (0.29)
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, 0.00]
0.00
0.00 (0.28)
0.00 (0.29)
0.00
Number of tests for microalbuminuria
...mean (sd)
0.86 (1.24)
0.86 (1.25)
0.00
0.63 (1.07)
0.64 (1.07)
-0.01
0.56 (0.79)
0.56 (0.76)
0.00
0.65 (0.98)
0.65 (0.97)
0.00
...median [IQR]
0.00 [0.00, 2.00]
0.00 [0.00, 2.00]
0.00
0.00 [0.00, 1.00]
0.00 [0.00, 1.00]
0.00
0.00 [0.00, 1.00]
0.00 [0.00, 1.00]
0.00
0.00 (0.98)
0.00 (0.97)
0.00
Total N distinct ICD9/ICD10 diagnoses at the 3rd 
digit level 
...mean (sd)
6.95 (8.39)
6.93 (8.40)
0.00
2.39 (4.45)
2.38 (4.64)
0.00
6.22 (8.51)
6.18 (8.55)
0.00
5.44 (7.68)
5.41 (7.73)
0.00
...median [IQR]
5.00 [0.00, 10.00]
5.00 [0.00, 10.00]
0.00
0.00 [0.00, 4.00]
0.00 [0.00, 4.00]
0.00
4.00 [0.00, 10.00]
3.00 [0.00, 10.00]
0.12
3.24 (7.68)
2.72 (7.73)
0.07
Use of thiazide; n (%)
2,737 (14.3%)
2,706 (14.1%)
0.005729859
2,745 (13.2%)
2,771 (13.3%) -0.00294956
6,857 (15.5%)
6,900 (15.5%)
0
12,339 (14.6%)
12,377 (14.7%)
0.00
Use of beta blockers; n (%)
8,557 (44.6%)
8,627 (45.0%)
-0.01
9,505 (45.7%)
9,500 (45.7%)
0.00
21,602 (48.7%)
21,620 (48.7%)
0.00
39,664 (47.0%)
39,747 (47.1%)
0.00
Use of calcium channel blockers; n (%)
5,718 (29.8%)
5,741 (29.9%)
0.00
6,185 (29.8%)
6,269 (30.2%)
-0.01
14,181 (32.0%)
14,361 (32.4%)
-0.01
26,084 (30.9%)
26,371 (31.3%)
-0.01
Table 1: Liraglutide vs DPP4i

AFTER PS MATCHING
Optum
MarketScan
Medicare
BEFORE PS MATCHING
The c-statistics for the propensity score model, pre-matching was 0.815. The post-matching c-statistic 
was 0.535.
The c-statistics for the propensity score model, pre-matching was 0.811. The post-matching 
c-statistic was 0.538.
The c-statistics for the propensity score model, pre-matching was 0.835. The post-matching c-statistic 
was 0.525.
Appendix B: Liraglutide vs 2nd Generation Sulfonylureas

Variable
Reference- 2nd 
Generation SUs
Exposure- Liraglutide
Reference- 2nd 
Generation SUs
Exposure- Liraglutide
Reference- 2nd 
Generation SUs
Exposure- 
Liraglutide
Reference- 2nd 
Generation SUs
Exposure- Liraglutide
St. Diff.
Number of patients
                                       196,712                                           12,485 
160,161
                                      
13,808
                                         
571,468
                                    
28,511
                       
                                       928,341                                           54,804 
Age
...mean (sd)
70.45 (7.97)
65.70 (6.79)
67.63 (9.31)
62.85 (6.12)
74.52 (7.40)
70.53 (4.98)
72.47 (7.88)
67.49 (5.73)
0.72
...median [IQR]
70.00 [65.00, 76.00]
66.00 [61.00, 70.00]
65.00 [61.00, 74.00]
62.00 [60.00, 65.00]
73.00 [68.00, 79.00]9.00 [67.00, 73.00]
70.98 (7.88)
66.55 (5.73)
0.64
Age categories 
...18 - 54; n (%)
4,772 (2.4%)
740 (5.9%)
7,998 (5.0%)
1,177 (8.5%)
0 (0.0%)
0 (0.0%)
12,770 (1.4%)
1,917 (3.5%)
-0.14
...55 - 64; n (%)
38,842 (19.7%)
4,610 (36.9%)
70,249 (43.9%)
8,602 (62.3%)
9,764 (1.7%)
694 (2.4%)
118,855 (12.8%)
13,906 (25.4%)
-0.32
...65 - 74; n (%)
93,525 (47.5%)
5,912 (47.4%)
44,191 (27.6%)
3,328 (24.1%)
313,203 (54.8%)
22,386 (78.5%)
450,919 (48.6%)
31,626 (57.7%)
-0.18
...>= 75; n (%)
59,573 (30.3%)
1,223 (9.8%)
37,723 (23.6%)
701 (5.1%)
248,501 (43.5%)
5,431 (19.0%)
345,797 (37.2%)
7,355 (13.4%)
0.57
Gender 
...Males; n (%)
102,630 (52.2%)
5,601 (44.9%)
91,138 (56.9%)
6,730 (48.7%)
260,001 (45.5%)
12,045 (42.2%)
453,769 (48.9%)
24,376 (44.5%)
0.09
...Females; n (%)
94,082 (47.8%)
6,884 (55.1%)
69,023 (43.1%)
7,078 (51.3%)
311,467 (54.5%)
16,466 (57.8%)
474,572 (51.1%)
30,428 (55.5%)
-0.09
Race 
...White; n (%)
N/A
N/A
N/A
N/A
439,116 (76.8%)
24,090 (84.5%)
439,116 (76.8%)
24,090 (84.5%)
-0.20
...Black; n (%)
N/A
N/A
N/A
N/A
69,514 (12.2%)
2,568 (9.0%)
69,514 (12.2%)
2,568 (9.0%)
0.10
...Asian; n (%)
N/A
N/A
N/A
N/A
19,245 (3.4%)
380 (1.3%)
19,245 (3.4%)
380 (1.3%)
0.14
...Hispanic; n (%)
N/A
N/A
N/A
N/A
22,497 (3.9%)
511 (1.8%)
22,497 (3.9%)
511 (1.8%)
0.13
...North American Native; n (%)
N/A
N/A
N/A
N/A
3,768 (0.7%)
122 (0.4%)
3,768 (0.7%)
122 (0.4%)
0.04
...Other/Unknown; n (%)
N/A
N/A
N/A
N/A
17,328 (3.0%)
840 (2.9%)
17,328 (3.0%)
840 (2.9%)
0.01
Region   (lumping missing&other category with West)
...Northeast; n (%)
21,016 (10.7%)
1,203 (9.6%)
28,601 (17.9%)
2,794 (20.2%)
94,259 (16.5%)
4,708 (16.5%)
143,876 (15.5%)
8,705 (15.9%)
-0.01
...South; n (%)
92,464 (47.0%)
6,770 (54.2%)
46,370 (29.0%)
2,793 (20.2%)
247,501 (43.3%)
13,088 (45.9%)
386,335 (41.6%)
22,651 (41.3%)
0.01
...Midwest; n (%)
38,854 (19.8%)
2,335 (18.7%)
61,418 (38.3%)
6,610 (47.9%)
138,467 (24.2%)
6,152 (21.6%)
238,739 (25.7%)
15,097 (27.5%)
-0.04
...West; n (%)
44,378 (22.6%)
2,177 (17.4%)
22,358 (14.0%)
1,452 (10.5%)
91,241 (16.0%)
4,563 (16.0%)
157,977 (17.0%)
8,192 (14.9%)
0.06
...Unknown+missing; n (%)
N/A
N/A
1,414 (0.9%)
159 (1.2%)
N/A
N/A
1,414 (0.9%)
159 (1.2%)
-0.03
CV Covariates
Ischemic heart disease; n (%)
55,227 (28.1%)
3,702 (29.7%)
52,321 (32.7%)
4,439 (32.1%)
187,624 (32.8%)
8,905 (31.2%)
295,172 (31.8%)
17,046 (31.1%)
0.02
Acute MI; n (%)
3,262 (1.7%)
174 (1.4%)
3,103 (1.9%)
212 (1.5%)
10,813 (1.9%)
338 (1.2%)
17,178 (1.9%)
724 (1.3%)
0.05
ACS/unstable angina; n (%)
3,647 (1.9%)
261 (2.1%)
3,557 (2.2%)
286 (2.1%)
11,272 (2.0%)
482 (1.7%)
18,476 (2.0%)
1,029 (1.9%)
0.01
Old MI; n (%)
8,091 (4.1%)
491 (3.9%)
4,508 (2.8%)
292 (2.1%)
26,566 (4.6%)
1,041 (3.7%)
39,165 (4.2%)
1,824 (3.3%)
0.05
Stable angina; n (%)
7,795 (4.0%)
598 (4.8%)
5,435 (3.4%)
500 (3.6%)
21,550 (3.8%)
1,130 (4.0%)
34,780 (3.7%)
2,228 (4.1%)
-0.02
Coronary atherosclerosis and other forms of chronic 
ischemic heart disease; n (%)
51,300 (26.1%)
3,479 (27.9%)
49,443 (30.9%)
4,229 (30.6%)
178,665 (31.3%)
8,493 (29.8%)
279,408 (30.1%)
16,201 (29.6%)
0.01
Other atherosclerosis with ICD10  ; n (%)
2,423 (1.2%)
121 (1.0%)
2,102 (1.3%)
159 (1.2%)
11,227 (2.0%)
473 (1.7%)
15,752 (1.7%)
753 (1.4%)
0.02
Previous cardiac procedure (CABG or PTCA or Stent) ; n (%)
1,607 (0.8%)
96 (0.8%)
1,929 (1.2%)
140 (1.0%)
4,469 (0.8%)
143 (0.5%)
8,005 (0.9%)
379 (0.7%)
0.02
History of CABG or PTCA; n (%)
12,855 (6.5%)
921 (7.4%)
6,551 (4.1%)
579 (4.2%)
53,044 (9.3%)
2,384 (8.4%)
72,450 (7.8%)
3,884 (7.1%)
0.03
Any stroke; n (%)
16,353 (8.3%)
905 (7.2%)
15,031 (9.4%)
1,024 (7.4%)
62,700 (11.0%)
2,451 (8.6%)
94,084 (10.1%)
4,380 (8.0%)
0.07
Ischemic stroke (w and w/o mention of cerebral 
infarction); n (%)
16,102 (8.2%)
900 (7.2%)
14,822 (9.3%)
1,006 (7.3%)
61,905 (10.8%)
2,428 (8.5%)
92,829 (10.0%)
4,334 (7.9%)
0.07
Hemorrhagic stroke; n (%)
545 (0.3%)
16 (0.1%)
459 (0.3%)
28 (0.2%)
2,008 (0.4%)
45 (0.2%)
3,012 (0.3%)
89 (0.2%)
0.02
TIA; n (%)
4,010 (2.0%)
233 (1.9%)
4,022 (2.5%)
242 (1.8%)
14,808 (2.6%)
516 (1.8%)
22,840 (2.5%)
991 (1.8%)
0.05
Other cerebrovascular disease; n (%)
4,639 (2.4%)
230 (1.8%)
3,239 (2.0%)
167 (1.2%)
19,559 (3.4%)
587 (2.1%)
27,437 (3.0%)
984 (1.8%)
0.08
Late effects of cerebrovascular disease; n (%)
4,527 (2.3%)
144 (1.2%)
2,805 (1.8%)
95 (0.7%)
18,669 (3.3%)
415 (1.5%)
26,001 (2.8%)
654 (1.2%)
0.11
Cerebrovascular procedure; n (%)
288 (0.1%)
12 (0.1%)
311 (0.2%)
11 (0.1%)
935 (0.2%)
26 (0.1%)
1,534 (0.2%)
49 (0.1%)
0.03
Heart failure (CHF); n (%)
21,366 (10.9%)
1,275 (10.2%)
16,040 (10.0%)
995 (7.2%)
84,892 (14.9%)
3,352 (11.8%)
122,298 (13.2%)
5,622 (10.3%)
0.09
Peripheral Vascular Disease (PVD) or PVD Surgery ; n (%)
18,962 (9.6%)
1,095 (8.8%)
14,043 (8.8%)
1,080 (7.8%)
73,310 (12.8%)
2,955 (10.4%)
106,315 (11.5%)
5,130 (9.4%)
0.07
Atrial fibrillation; n (%)
18,759 (9.5%)
962 (7.7%)
13,972 (8.7%)
789 (5.7%)
81,612 (14.3%)
3,081 (10.8%)
114,343 (12.3%)
4,832 (8.8%)
0.11
Other cardiac dysrhythmia; n (%)
21,281 (10.8%)
1,309 (10.5%)
14,014 (8.7%)
949 (6.9%)
82,684 (14.5%)
3,363 (11.8%)
117,979 (12.7%)
5,621 (10.3%)
0.08
Cardiac conduction disorders; n (%)
6,617 (3.4%)
355 (2.8%)
4,460 (2.8%)
289 (2.1%)
28,034 (4.9%)
1,077 (3.8%)
39,111 (4.2%)
1,721 (3.1%)
0.06
Other CVD; n (%)
26,092 (13.3%)
1,498 (12.0%)
20,400 (12.7%)
1,465 (10.6%)
99,284 (17.4%)
4,174 (14.6%)
145,776 (15.7%)
7,137 (13.0%)
0.08
Diabetes-related complications
Diabetic retinopathy; n (%)
11,089 (5.6%)
956 (7.7%)
6,538 (4.1%)
659 (4.8%)
32,274 (5.6%)
2,394 (8.4%)
49,901 (5.4%)
4,009 (7.3%)
-0.08
Diabetes with other ophthalmic manifestations; n (%)
1,424 (0.7%)
91 (0.7%)
4,704 (2.9%)
449 (3.3%)
13,704 (2.4%)
880 (3.1%)
19,832 (2.1%)
1,420 (2.6%)
-0.03
Retinal detachment, vitreous hemorrhage, vitrectomy; n 
(%)
717 (0.4%)
54 (0.4%)
464 (0.3%)
47 (0.3%)
1,892 (0.3%)
138 (0.5%)
3,073 (0.3%)
239 (0.4%)
-0.02
Retinal laser coagulation therapy; n (%)
944 (0.5%)
75 (0.6%)
860 (0.5%)
92 (0.7%)
2,550 (0.4%)
201 (0.7%)
4,354 (0.5%)
368 (0.7%)
-0.03
Occurrence of Diabetic Neuropathy  ; n (%)
34,538 (17.6%)
2,995 (24.0%)
17,014 (10.6%)
1,961 (14.2%)
95,926 (16.8%)
6,700 (23.5%)
147,478 (15.9%)
11,656 (21.3%)
-0.14
Unmatched
Optum
MarketScan
Medicare
POOLED
Table 1: Liraglutide vs 2nd Generation Sulfonylureas

Occurrence of diabetic nephropathy  with ICD10 ; n (%)
31,872 (16.2%)
2,161 (17.3%)
11,026 (6.9%)
1,042 (7.5%)
54,295 (9.5%)
3,539 (12.4%)
97,193 (10.5%)
6,742 (12.3%)
-0.06
Hypoglycemia ; n (%)
5,003 (2.5%)
275 (2.2%)
5,026 (3.1%)
413 (3.0%)
16,139 (2.8%)
853 (3.0%)
26,168 (2.8%)
1,541 (2.8%)
0.00
Hyperglycemia; n (%)
8,676 (4.4%)
579 (4.6%)
5,054 (3.2%)
429 (3.1%)
29,706 (5.2%)
1,240 (4.3%)
43,436 (4.7%)
2,248 (4.1%)
0.03
Disorders of fluid electrolyte and acid-base balance; n (%)
17,943 (9.1%)
827 (6.6%)
11,019 (6.9%)
607 (4.4%)
69,422 (12.1%)
2,164 (7.6%)
98,384 (10.6%)
3,598 (6.6%)
0.14
Diabetic ketoacidosis; n (%)
210 (0.1%)
14 (0.1%)
153 (0.1%)
17 (0.1%)
731 (0.1%)
33 (0.1%)
1,094 (0.1%)
64 (0.1%)
0.00
Hyperosmolar hyperglycemic nonketotic syndrome 
(HONK); n (%)
1,026 (0.5%)
70 (0.6%)
579 (0.4%)
44 (0.3%)
2,876 (0.5%)
128 (0.4%)
4,481 (0.5%)
242 (0.4%)
0.01
Diabetes with peripheral circulatory disorders with ICD-
10  ; n (%)
15,191 (7.7%)
987 (7.9%)
6,670 (4.2%)
540 (3.9%)
42,778 (7.5%)
2,040 (7.2%)
64,639 (7.0%)
3,567 (6.5%)
0.02
Diabetic Foot; n (%)
4,860 (2.5%)
320 (2.6%)
3,959 (2.5%)
304 (2.2%)
18,615 (3.3%)
940 (3.3%)
27,434 (3.0%)
1,564 (2.9%)
0.01
Gangrene ; n (%)
669 (0.3%)
34 (0.3%)
552 (0.3%)
20 (0.1%)
2,088 (0.4%)
60 (0.2%)
3,309 (0.4%)
114 (0.2%)
0.04
Lower extremity amputation; n (%)
1,382 (0.7%)
109 (0.9%)
710 (0.4%)
41 (0.3%)
4,515 (0.8%)
165 (0.6%)
6,607 (0.7%)
315 (0.6%)
0.01
Osteomyelitis; n (%)
1,371 (0.7%)
88 (0.7%)
1,120 (0.7%)
66 (0.5%)
4,379 (0.8%)
168 (0.6%)
6,870 (0.7%)
322 (0.6%)
0.01
Skin infections ; n (%)
11,149 (5.7%)
742 (5.9%)
9,819 (6.1%)
811 (5.9%)
43,277 (7.6%)
2,258 (7.9%)
64,245 (6.9%)
3,811 (7.0%)
0.00
Erectile dysfunction; n (%)
4,789 (2.4%)
360 (2.9%)
3,269 (2.0%)
318 (2.3%)
10,887 (1.9%)
833 (2.9%)
18,945 (2.0%)
1,511 (2.8%)
-0.05
Diabetes with unspecified complication; n (%)
9,112 (4.6%)
827 (6.6%)
5,419 (3.4%)
659 (4.8%)
25,116 (4.4%)
1,673 (5.9%)
39,647 (4.3%)
3,159 (5.8%)
-0.07
Diabetes mellitus without mention of complications; n 
(%)
174,528 (88.7%)
10,824 (86.7%)
150,098 (93.7%)
12,905 (93.5%)
539,347 (94.4%)
26,472 (92.8%)
863,973 (93.1%)
50,201 (91.6%)
0.06
Hypertension: 1 inpatient or 2 outpatient claims within 
365 days; n (%)
185,514 (94.3%)
11,887 (95.2%)
139,282 (87.0%)
12,287 (89.0%)
550,194 (96.3%)
27,630 (96.9%)
874,990 (94.3%)
51,804 (94.5%)
-0.01
Hyperlipidemia ; n (%)
144,099 (73.3%)
9,851 (78.9%)
99,840 (62.3%)
9,823 (71.1%)
435,198 (76.2%)
23,633 (82.9%)
679,137 (73.2%)
43,307 (79.0%)
-0.14
Edema; n (%)
14,841 (7.5%)
1,088 (8.7%)
9,129 (5.7%)
846 (6.1%)
62,616 (11.0%)
3,218 (11.3%)
86,586 (9.3%)
5,152 (9.4%)
0.00
Renal Dysfunction (non-diabetic) ; n (%)
50,792 (25.8%)
2,889 (23.1%)
27,130 (16.9%)
1,892 (13.7%)
141,930 (24.8%)
6,290 (22.1%)
219,852 (23.7%)
11,071 (20.2%)
0.08
Occurrence of acute renal disease ; n (%)
9,401 (4.8%)
369 (3.0%)
6,016 (3.8%)
216 (1.6%)
35,473 (6.2%)
909 (3.2%)
50,890 (5.5%)
1,494 (2.7%)
0.14
Occurrence of chronic renal insufficiency; n (%)
42,651 (21.7%)
2,481 (19.9%)
19,946 (12.5%)
1,449 (10.5%)
116,950 (20.5%)
5,396 (18.9%)
179,547 (19.3%)
9,326 (17.0%)
0.06
Chronic kidney disease ; n (%)
41,223 (21.0%)
2,405 (19.3%)
19,353 (12.1%)
1,392 (10.1%)
111,247 (19.5%)
5,116 (17.9%)
171,823 (18.5%)
8,913 (16.3%)
0.06
CKD Stage 3-4; n (%)
29,293 (14.9%)
1,735 (13.9%)
13,900 (8.7%)
1,030 (7.5%)
76,878 (13.5%)
3,680 (12.9%)
120,071 (12.9%)
6,445 (11.8%)
0.03
Occurrence of hypertensive nephropathy; n (%)
18,774 (9.5%)
1,084 (8.7%)
8,031 (5.0%)
535 (3.9%)
56,974 (10.0%)
2,269 (8.0%)
83,779 (9.0%)
3,888 (7.1%)
0.07
Occurrence of miscellaneous renal insufficiency ; n (%)
12,325 (6.3%)
641 (5.1%)
7,652 (4.8%)
513 (3.7%)
45,632 (8.0%)
1,823 (6.4%)
65,609 (7.1%)
2,977 (5.4%)
0.07
Glaucoma or cataracts ; n (%)
41,679 (21.2%)
2,571 (20.6%)
28,496 (17.8%)
2,350 (17.0%)
144,998 (25.4%)
8,094 (28.4%)
215,173 (23.2%)
13,015 (23.7%)
-0.01
Cellulitis or abscess of toe; n (%)
2,852 (1.4%)
189 (1.5%)
1,698 (1.1%)
126 (0.9%)
9,051 (1.6%)
446 (1.6%)
13,601 (1.5%)
761 (1.4%)
0.01
Foot ulcer; n (%)
4,802 (2.4%)
302 (2.4%)
4,015 (2.5%)
304 (2.2%)
18,697 (3.3%)
921 (3.2%)
27,514 (3.0%)
1,527 (2.8%)
0.01
Bladder stones; n (%)
269 (0.1%)
8 (0.1%)
223 (0.1%)
14 (0.1%)
1,039 (0.2%)
41 (0.1%)
1,531 (0.2%)
63 (0.1%)
0.03
Kidney stones; n (%)
4,100 (2.1%)
318 (2.5%)
3,487 (2.2%)
341 (2.5%)
14,180 (2.5%)
805 (2.8%)
21,767 (2.3%)
1,464 (2.7%)
-0.03
Urinary tract infections (UTIs); n (%)
19,351 (9.8%)
1,136 (9.1%)
11,757 (7.3%)
940 (6.8%)
84,914 (14.9%)
3,659 (12.8%)
116,022 (12.5%)
5,735 (10.5%)
0.06
Dipstick urinalysis; n (%)
68,120 (34.6%)
4,493 (36.0%)
46,700 (29.2%)
4,559 (33.0%)
223,752 (39.2%)
11,639 (40.8%)
338,572 (36.5%)
20,691 (37.8%)
-0.03
Non-dipstick urinalysis; n (%)
76,422 (38.8%)
5,479 (43.9%)
42,377 (26.5%)
4,897 (35.5%)
205,498 (36.0%)
13,140 (46.1%)
324,297 (34.9%)
23,516 (42.9%)
-0.16
Urine function test; n (%)
4,806 (2.4%)
280 (2.2%)
4,075 (2.5%)
345 (2.5%)
17,903 (3.1%)
986 (3.5%)
26,784 (2.9%)
1,611 (2.9%)
0.00
Cytology; n (%)
1,477 (0.8%)
85 (0.7%)
1,544 (1.0%)
115 (0.8%)
5,802 (1.0%)
288 (1.0%)
8,823 (1.0%)
488 (0.9%)
0.01
Cystos; n (%)
2,368 (1.2%)
147 (1.2%)
2,245 (1.4%)
176 (1.3%)
8,292 (1.5%)
418 (1.5%)
12,905 (1.4%)
741 (1.4%)
0.00
Other Covariates
Liver disease; n (%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
#VALUE!
000 (0.0%)
#VALUE!
Osteoarthritis; n (%)
33,853 (17.2%)
2,542 (20.4%)
21,855 (13.6%)
2,219 (16.1%)
136,870 (24.0%)
7,450 (26.1%)
192,578 (20.7%)
12,211 (22.3%)
-0.04
Other arthritis, arthropathies and musculoskeletal pain; n 
(%)
71,081 (36.1%)
5,138 (41.2%)
53,785 (33.6%)
5,188 (37.6%)
259,992 (45.5%)
13,940 (48.9%)
384,858 (41.5%)
24,266 (44.3%)
-0.06
Dorsopathies; n (%)
41,440 (21.1%)
3,364 (26.9%)
30,075 (18.8%)
3,095 (22.4%)
150,059 (26.3%)
8,971 (31.5%)
221,574 (23.9%)
15,430 (28.2%)
-0.10
Fractures; n (%)
6,554 (3.3%)
371 (3.0%)
5,196 (3.2%)
351 (2.5%)
26,453 (4.6%)
1,070 (3.8%)
38,203 (4.1%)
1,792 (3.3%)
0.04
Falls ; n (%)
7,893 (4.0%)
372 (3.0%)
2,427 (1.5%)
138 (1.0%)
31,012 (5.4%)
971 (3.4%)
41,332 (4.5%)
1,481 (2.7%)
0.10
Osteoporosis; n (%)
10,537 (5.4%)
556 (4.5%)
5,586 (3.5%)
427 (3.1%)
44,053 (7.7%)
2,028 (7.1%)
60,176 (6.5%)
3,011 (5.5%)
0.04
Hyperthyroidism; n (%)
1,325 (0.7%)
102 (0.8%)
756 (0.5%)
72 (0.5%)
5,224 (0.9%)
285 (1.0%)
7,305 (0.8%)
459 (0.8%)
0.00
Hypothyroidism ; n (%)
29,473 (15.0%)
2,544 (20.4%)
16,299 (10.2%)
2,095 (15.2%)
84,955 (14.9%)
5,114 (17.9%)
130,727 (14.1%)
9,753 (17.8%)
-0.10
Other disorders of thyroid gland ; n (%)
5,691 (2.9%)
690 (5.5%)
3,833 (2.4%)
717 (5.2%)
19,904 (3.5%)
1,782 (6.3%)
29,428 (3.2%)
3,189 (5.8%)
-0.13
Depression; n (%)
15,620 (7.9%)
1,336 (10.7%)
10,206 (6.4%)
1,173 (8.5%)
65,406 (11.4%)
3,664 (12.9%)
91,232 (9.8%)
6,173 (11.3%)
-0.05
Anxiety; n (%)
12,813 (6.5%)
1,186 (9.5%)
6,953 (4.3%)
770 (5.6%)
50,865 (8.9%)
2,569 (9.0%)
70,631 (7.6%)
4,525 (8.3%)
-0.03
Sleep_Disorder; n (%)
12,444 (6.3%)
1,304 (10.4%)
13,885 (8.7%)
2,243 (16.2%)
49,765 (8.7%)
3,988 (14.0%)
76,094 (8.2%)
7,535 (13.7%)
-0.18
Dementia; n (%)
10,450 (5.3%)
258 (2.1%)
6,100 (3.8%)
146 (1.1%)
54,395 (9.5%)
1,006 (3.5%)
70,945 (7.6%)
1,410 (2.6%)
0.23
Delirium; n (%)
3,084 (1.6%)
93 (0.7%)
2,269 (1.4%)
69 (0.5%)
16,516 (2.9%)
351 (1.2%)
21,869 (2.4%)
513 (0.9%)
0.12
Psychosis; n (%)
2,498 (1.3%)
81 (0.6%)
1,727 (1.1%)
57 (0.4%)
15,982 (2.8%)
256 (0.9%)
20,207 (2.2%)
394 (0.7%)
0.13
Obesity; n (%)
31,831 (16.2%)
4,320 (34.6%)
16,930 (10.6%)
3,086 (22.3%)
77,359 (13.5%)
7,939 (27.8%)
126,120 (13.6%)
15,345 (28.0%)
-0.36
Overweight; n (%)
9,079 (4.6%)
534 (4.3%)
2,442 (1.5%)
267 (1.9%)
17,903 (3.1%)
820 (2.9%)
29,424 (3.2%)
1,621 (3.0%)
0.01
Smoking; n (%)
20,336 (10.3%)
1,403 (11.2%)
8,760 (5.5%)
632 (4.6%)
77,008 (13.5%)
3,563 (12.5%)
106,104 (11.4%)
5,598 (10.2%)
0.04
Alcohol abuse or dependence; n (%)
1,443 (0.7%)
47 (0.4%)
840 (0.5%)
38 (0.3%)
4,133 (0.7%)
97 (0.3%)
6,416 (0.7%)
182 (0.3%)
0.06
Drug abuse or dependence; n (%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
#VALUE!
00 (0.0%)
#VALUE!
COPD; n (%)
17,677 (9.0%)
1,036 (8.3%)
10,715 (6.7%)
671 (4.9%)
76,066 (13.3%)
3,280 (11.5%)
104,458 (11.3%)
4,987 (9.1%)
0.07
Table 1: Liraglutide vs 2nd Generation Sulfonylureas

Asthma; n (%)
9,916 (5.0%)
930 (7.4%)
6,975 (4.4%)
821 (5.9%)
37,105 (6.5%)
2,443 (8.6%)
53,996 (5.8%)
4,194 (7.7%)
-0.08
Obstructive sleep apnea; n (%)
14,202 (7.2%)
2,283 (18.3%)
12,619 (7.9%)
2,406 (17.4%)
38,734 (6.8%)
4,306 (15.1%)
65,555 (7.1%)
8,995 (16.4%)
-0.29
Pneumonia; n (%)
5,880 (3.0%)
256 (2.1%)
4,981 (3.1%)
241 (1.7%)
28,237 (4.9%)
795 (2.8%)
39,098 (4.2%)
1,292 (2.4%)
0.10
Imaging; n (%)
349 (0.2%)
15 (0.1%)
247 (0.2%)
10 (0.1%)
1,541 (0.3%)
34 (0.1%)
2,137 (0.2%)
59 (0.1%)
0.03
Diabetes Medications
DM Medications - AGIs; n (%)
658 (0.3%)
40 (0.3%)
522 (0.3%)
48 (0.3%)
2,010 (0.4%)
121 (0.4%)
3,190 (0.3%)
209 (0.4%)
-0.02
DM Medications - Glitazones; n (%)
16,520 (8.4%)
1,216 (9.7%)
17,287 (10.8%)
1,827 (13.2%)
37,921 (6.6%)
2,572 (9.0%)
71,728 (7.7%)
5,615 (10.2%)
-0.09
DM Medications - Insulin; n (%)
11,363 (5.8%)
2,682 (21.5%)
9,783 (6.1%)
2,740 (19.8%)
40,963 (7.2%)
7,037 (24.7%)
62,109 (6.7%)
12,459 (22.7%)
-0.46
DM Medications - Meglitinides; n (%)
1,281 (0.7%)
146 (1.2%)
1,525 (1.0%)
311 (2.3%)
5,854 (1.0%)
590 (2.1%)
8,660 (0.9%)
1,047 (1.9%)
-0.09
DM Medications - Metformin; n (%)
125,476 (63.8%)
7,325 (58.7%)
100,419 (62.7%)
8,570 (62.1%)
355,150 (62.1%)
17,242 (60.5%)
581,045 (62.6%)
33,137 (60.5%)
0.04
Concomitant initiation or current use of SGLT2i; n (%)
2,699 (1.4%)
717 (5.7%)
1,961 (1.2%)
731 (5.3%)
4,774 (0.8%)
1,220 (4.3%)
9,434 (1.0%)
2,668 (4.9%)
-0.23
Concomitant initiation or current use of AGIs; n (%)
472 (0.2%)
22 (0.2%)
391 (0.2%)
29 (0.2%)
1,434 (0.3%)
83 (0.3%)
2,297 (0.2%)
134 (0.2%)
0.00
Concomitant initiation or current use of Glitazones; n (%)
12,440 (6.3%)
873 (7.0%)
12,991 (8.1%)
1,304 (9.4%)
28,770 (5.0%)
1,961 (6.9%)
54,201 (5.8%)
4,138 (7.6%)
-0.07
Concomitant initiation or current use of DPP4i ; n (%)
4,204 (2.1%)
109 (0.9%)
4,943 (3.1%)
124 (0.9%)
13,128 (2.3%)
225 (0.8%)
22,275 (2.4%)
#VALUE!
#VALUE!
Concomitant initiation or current use of Insulin; n (%)
6,048 (3.1%)
1,683 (13.5%)
5,661 (3.5%)
1,712 (12.4%)
22,161 (3.9%)
4,433 (15.5%)
33,870 (3.6%)
7,828 (14.3%)
-0.38
Concomitant initiation or current use of Meglitinides; n 
(%)
781 (0.4%)
86 (0.7%)
931 (0.6%)
215 (1.6%)
3,651 (0.6%)
402 (1.4%)
5,363 (0.6%)
703 (1.3%)
-0.07
Concomitant initiation or current use of Metformin; n (%)
105,292 (53.5%)
5,852 (46.9%)
83,840 (52.3%)
6,810 (49.3%)
296,366 (51.9%)
13,865 (48.6%)
485,498 (52.3%)
26,527 (48.4%)
0.08
Past use of SGLT2i  ; n (%)
1,362 (0.7%)
294 (2.4%)
795 (0.5%)
249 (1.8%)
2,664 (0.5%)
540 (1.9%)
4,821 (0.5%)
1,083 (2.0%)
-0.14
Past use of AGIs ; n (%)
186 (0.1%)
18 (0.1%)
131 (0.1%)
19 (0.1%)
576 (0.1%)
38 (0.1%)
893 (0.1%)
75 (0.1%)
0.00
Past use of Glitazones  ; n (%)
4,080 (2.1%)
343 (2.7%)
4,296 (2.7%)
523 (3.8%)
9,151 (1.6%)
611 (2.1%)
17,527 (1.9%)
1,477 (2.7%)
-0.05
Past use of DPP4i  ; n (%)
4,798 (2.4%)
474 (3.8%)
4,852 (3.0%)
747 (5.4%)
17,036 (3.0%)
1,321 (4.6%)
26,686 (2.9%)
2,542 (4.6%)
-0.09
Past use of Insulin  ; n (%)
5,316 (2.7%)
999 (8.0%)
4,122 (2.6%)
1,028 (7.4%)
18,807 (3.3%)
2,604 (9.1%)
28,245 (3.0%)
4,631 (8.5%)
-0.24
Past use of Meglitinides  ; n (%)
500 (0.3%)
60 (0.5%)
594 (0.4%)
96 (0.7%)
2,203 (0.4%)
188 (0.7%)
3,297 (0.4%)
344 (0.6%)
-0.03
Past use of metformin (final)  ; n (%)
20,184 (10.3%)
1,473 (11.8%)
16,579 (10.4%)
1,760 (12.7%)
58,784 (10.3%)
3,377 (11.8%)
95,547 (10.3%)
6,610 (12.1%)
-0.06
Other Medications
Use of ACE inhibitors; n (%)
95,481 (48.5%)
5,189 (41.6%)
75,829 (47.3%)
5,623 (40.7%)
267,223 (46.8%)
11,669 (40.9%)
438,533 (47.2%)
22,481 (41.0%)
0.13
Use of ARBs; n (%)
50,472 (25.7%)
4,265 (34.2%)
43,683 (27.3%)
5,149 (37.3%)
155,237 (27.2%)
10,277 (36.0%)
249,392 (26.9%)
19,691 (35.9%)
-0.19
Use of Loop Diuretics ; n (%)
29,814 (15.2%)
2,153 (17.2%)
25,579 (16.0%)
2,138 (15.5%)
122,938 (21.5%)
6,242 (21.9%)
178,331 (19.2%)
10,533 (19.2%)
0.00
Use of other diuretics; n (%)
6,145 (3.1%)
543 (4.3%)
5,612 (3.5%)
609 (4.4%)
22,856 (4.0%)
1,451 (5.1%)
34,613 (3.7%)
2,603 (4.7%)
-0.05
Use of nitrates-United; n (%)
13,013 (6.6%)
889 (7.1%)
13,267 (8.3%)
986 (7.1%)
50,608 (8.9%)
2,246 (7.9%)
76,888 (8.3%)
4,121 (7.5%)
0.03
Use of other hypertension drugs; n (%)
17,387 (8.8%)
893 (7.2%)
13,879 (8.7%)
917 (6.6%)
55,688 (9.7%)
2,257 (7.9%)
86,954 (9.4%)
4,067 (7.4%)
0.07
Use of digoxin; n (%)
4,907 (2.5%)
177 (1.4%)
4,877 (3.0%)
221 (1.6%)
22,362 (3.9%)
602 (2.1%)
32,146 (3.5%)
1,000 (1.8%)
0.11
Use of Anti-arrhythmics; n (%)
3,586 (1.8%)
208 (1.7%)
3,575 (2.2%)
229 (1.7%)
15,299 (2.7%)
638 (2.2%)
22,460 (2.4%)
1,075 (2.0%)
0.03
Use of COPD/asthma meds; n (%)
24,498 (12.5%)
2,132 (17.1%)
21,896 (13.7%)
2,435 (17.6%)
92,859 (16.2%)
5,747 (20.2%)
139,253 (15.0%)
10,314 (18.8%)
-0.10
Use of statins; n (%)
129,470 (65.8%)
8,672 (69.5%)
104,551 (65.3%)
9,624 (69.7%)
379,136 (66.3%)
20,297 (71.2%)
613,157 (66.0%)
38,593 (70.4%)
-0.09
Use of other lipid-lowering drugs; n (%)
20,454 (10.4%)
1,705 (13.7%)
22,311 (13.9%)
2,476 (17.9%)
62,387 (10.9%)
4,234 (14.9%)
105,152 (11.3%)
8,415 (15.4%)
-0.12
Use of antiplatelet agents; n (%)
26,712 (13.6%)
1,885 (15.1%)
29,039 (18.1%)
2,574 (18.6%)
88,937 (15.6%)
4,508 (15.8%)
144,688 (15.6%)
8,967 (16.4%)
-0.02
Use of oral anticoagulants (Dabigatran, Rivaroxaban, 
Apixaban, Warfarin); n (%)
15,431 (7.8%)
898 (7.2%)
13,337 (8.3%)
865 (6.3%)
64,168 (11.2%)
2,746 (9.6%)
92,936 (10.0%)
4,509 (8.2%)
0.06
Use of heparin and other low-molecular weight heparins; 
n (%)
997 (0.5%)
70 (0.6%)
42 (0.0%)
0 (0.0%)
3,443 (0.6%)
141 (0.5%)
4,482 (0.5%)
211 (0.4%)
0.01
Use of NSAIDs; n (%)
27,926 (14.2%)
2,195 (17.6%)
22,554 (14.1%)
2,437 (17.6%)
88,637 (15.5%)
5,192 (18.2%)
139,117 (15.0%)
9,824 (17.9%)
-0.08
Use of oral corticosteroids; n (%)
29,383 (14.9%)
2,095 (16.8%)
24,298 (15.2%)
2,189 (15.9%)
105,691 (18.5%)
5,314 (18.6%)
159,372 (17.2%)
9,598 (17.5%)
-0.01
Use of bisphosphonate (United); n (%)
5,538 (2.8%)
246 (2.0%)
3,396 (2.1%)
213 (1.5%)
18,770 (3.3%)
730 (2.6%)
27,704 (3.0%)
1,189 (2.2%)
0.05
Use of opioids; n (%)
46,368 (23.6%)
3,558 (28.5%)
41,697 (26.0%)
3,960 (28.7%)
152,202 (26.6%)
8,558 (30.0%)
240,267 (25.9%)
16,076 (29.3%)
-0.08
Use of antidepressants; n (%)
40,204 (20.4%)
3,993 (32.0%)
32,509 (20.3%)
4,226 (30.6%)
141,130 (24.7%)
9,732 (34.1%)
213,843 (23.0%)
17,951 (32.8%)
-0.22
Use of antipsychotics; n (%)
4,150 (2.1%)
303 (2.4%)
3,031 (1.9%)
263 (1.9%)
20,868 (3.7%)
741 (2.6%)
28,049 (3.0%)
1,307 (2.4%)
0.04
Use of anticonvulsants; n (%)
27,511 (14.0%)
2,594 (20.8%)
18,209 (11.4%)
2,061 (14.9%)
93,566 (16.4%)
5,868 (20.6%)
139,286 (15.0%)
10,523 (19.2%)
-0.11
Use of lithium; n (%)
205 (0.1%)
12 (0.1%)
203 (0.1%)
16 (0.1%)
735 (0.1%)
38 (0.1%)
1,143 (0.1%)
066 (0.1%)
0.00
Use of Benzos; n (%)
15,195 (7.7%)
1,491 (11.9%)
16,820 (10.5%)
1,814 (13.1%)
56,618 (9.9%)
3,401 (11.9%)
88,633 (9.5%)
6,706 (12.2%)
-0.09
Use of anxiolytics/hypnotics; n (%)
9,918 (5.0%)
963 (7.7%)
9,756 (6.1%)
1,225 (8.9%)
34,826 (6.1%)
2,308 (8.1%)
54,500 (5.9%)
4,496 (8.2%)
-0.09
Use of dementia meds; n (%)
5,629 (2.9%)
120 (1.0%)
3,983 (2.5%)
99 (0.7%)
30,389 (5.3%)
615 (2.2%)
40,001 (4.3%)
834 (1.5%)
0.17
Use of antiparkinsonian meds; n (%)
4,469 (2.3%)
437 (3.5%)
3,486 (2.2%)
441 (3.2%)
19,549 (3.4%)
1,259 (4.4%)
27,504 (3.0%)
2,137 (3.9%)
-0.05
Any use of pramlintide; n (%)
3 (0.0%)
5 (0.0%)
8 (0.0%)
25 (0.2%)
**
**
**
**
**
Any use of 1st generation sulfonylureas; n (%)
75 (0.0%)
0 (0.0%)
164 (0.1%)
1 (0.0%)
**
**
**
**
**
Entresto (sacubitril/valsartan); n (%)
199 (0.1%)
38 (0.3%)
56 (0.0%)
9 (0.1%)
291 (0.1%)
26 (0.1%)
546 (0.1%)
073 (0.1%)
0.00
Initiation as monotherapy  ; n (%)
34,741 (17.7%)
1,801 (14.4%)
25,845 (16.1%)
1,561 (11.3%)
86,804 (15.2%)
2,776 (9.7%)
147,390 (15.9%)
6,138 (11.2%)
0.14
Labs
                                       356,873                                           26,293 
Lab values- HbA1c (%) ; n (%)
64,253 (32.7%)
4,705 (37.7%)
10,520 (6.6%)
752 (5.4%)
N/A
N/A
74,773 (21.0%)
5,457 (20.8%)
0.00
Lab values- HbA1c (%) (within 3 months) ; n (%)
49,248 (25.0%)
3,593 (28.8%)
8,071 (5.0%)
591 (4.3%)
N/A
N/A
57,319 (16.1%)
4,184 (15.9%)
0.01
Lab values- HbA1c (%) (within 6 months) ; n (%)
64,253 (32.7%)
4,705 (37.7%)
10,520 (6.6%)
752 (5.4%)
N/A
N/A
74,773 (21.0%)
5,457 (20.8%)
0.00
Table 1: Liraglutide vs 2nd Generation Sulfonylureas

Lab values- BNP; n (%)
1,407 (0.7%)
128 (1.0%)
199 (0.1%)
24 (0.2%)
N/A
N/A
1,606 (0.5%)
152 (0.6%)
-0.01
Lab values- BNP (within 3 months); n (%)
867 (0.4%)
84 (0.7%)
137 (0.1%)
21 (0.2%)
N/A
N/A
1,004 (0.3%)
105 (0.4%)
-0.02
Lab values- BNP (within 6 months); n (%)
1,407 (0.7%)
128 (1.0%)
199 (0.1%)
24 (0.2%)
N/A
N/A
1,606 (0.5%)
152 (0.6%)
-0.01
Lab values- BUN (mg/dl); n (%)
65,450 (33.3%)
4,847 (38.8%)
7,968 (5.0%)
784 (5.7%)
N/A
N/A
73,418 (20.6%)
5,631 (21.4%)
-0.02
Lab values- BUN (mg/dl) (within 3 months); n (%)
49,920 (25.4%)
3,669 (29.4%)
5,916 (3.7%)
596 (4.3%)
N/A
N/A
55,836 (15.6%)
4,265 (16.2%)
-0.02
Lab values- BUN (mg/dl) (within 6 months); n (%)
65,450 (33.3%)
4,847 (38.8%)
7,968 (5.0%)
784 (5.7%)
N/A
N/A
73,418 (20.6%)
5,631 (21.4%)
-0.02
Lab values- Creatinine (mg/dl) ; n (%)
66,968 (34.0%)
5,002 (40.1%)
8,308 (5.2%)
816 (5.9%)
N/A
N/A
75,276 (21.1%)
5,818 (22.1%)
-0.02
Lab values- Creatinine (mg/dl) (within 3 months) ; n (%)
51,084 (26.0%)
3,790 (30.4%)
6,181 (3.9%)
620 (4.5%)
N/A
N/A
57,265 (16.0%)
4,410 (16.8%)
-0.02
Lab values- Creatinine (mg/dl) (within 6 months) ; n (%)
66,968 (34.0%)
5,002 (40.1%)
8,308 (5.2%)
816 (5.9%)
N/A
N/A
75,276 (21.1%)
5,818 (22.1%)
-0.02
Lab values- HDL level (mg/dl); n (%)
53,958 (27.4%)
4,018 (32.2%)
8,896 (5.6%)
697 (5.0%)
N/A
N/A
62,854 (17.6%)
4,715 (17.9%)
-0.01
Lab values- HDL level (mg/dl) (within 3 months); n (%)
38,832 (19.7%)
2,867 (23.0%)
6,324 (3.9%)
519 (3.8%)
N/A
N/A
45,156 (12.7%)
3,386 (12.9%)
-0.01
Lab values- HDL level (mg/dl) (within 6 months); n (%)
53,958 (27.4%)
4,018 (32.2%)
8,896 (5.6%)
697 (5.0%)
N/A
N/A
62,854 (17.6%)
4,715 (17.9%)
-0.01
Lab values- LDL level (mg/dl) ; n (%)
55,693 (28.3%)
4,146 (33.2%)
9,674 (6.0%)
720 (5.2%)
N/A
N/A
65,367 (18.3%)
4,866 (18.5%)
-0.01
Lab values- LDL level (mg/dl) (within 3 months) ; n (%)
40,047 (20.4%)
2,966 (23.8%)
6,888 (4.3%)
531 (3.8%)
N/A
N/A
46,935 (13.2%)
3,497 (13.3%)
0.00
Lab values- LDL level (mg/dl) (within 6 months) ; n (%)
55,693 (28.3%)
4,146 (33.2%)
9,674 (6.0%)
720 (5.2%)
N/A
N/A
65,367 (18.3%)
4,866 (18.5%)
-0.01
Lab values- NT-proBNP; n (%)
178 (0.1%)
30 (0.2%)
15 (0.0%)
3 (0.0%)
N/A
N/A
193 (0.1%)
33 (0.1%)
0.00
Lab values- NT-proBNP (within 3 months); n (%)
108 (0.1%)
20 (0.2%)
8 (0.0%)
1 (0.0%)
N/A
N/A
116 (0.0%)
21 (0.1%)
-
Lab values- NT-proBNP (within 6 months); n (%)
178 (0.1%)
30 (0.2%)
15 (0.0%)
3 (0.0%)
N/A
N/A
193 (0.1%)
33 (0.1%)
-
Lab values- Total cholesterol (mg/dl) ; n (%)
54,700 (27.8%)
4,119 (33.0%)
9,020 (5.6%)
707 (5.1%)
N/A
N/A
63,720 (17.9%)
4,826 (18.4%)
-0.01
Lab values- Total cholesterol (mg/dl) (within 3 months) ; n 
(%)
39,389 (20.0%)
2,940 (23.5%)
6,388 (4.0%)
528 (3.8%)
N/A
N/A
45,777 (12.8%)
3,468 (13.2%)
-0.01
Lab values- Total cholesterol (mg/dl) (within 6 months) ; n 
(%)
54,700 (27.8%)
4,119 (33.0%)
9,020 (5.6%)
707 (5.1%)
N/A
N/A
63,720 (17.9%)
4,826 (18.4%)
-0.01
Lab values- Triglyceride level (mg/dl); n (%)
54,124 (27.5%)
4,074 (32.6%)
8,795 (5.5%)
692 (5.0%)
N/A
N/A
62,919 (17.6%)
4,766 (18.1%)
-0.01
Lab values- Triglyceride level (mg/dl) (within 3 months); n 
(%)
39,010 (19.8%)
2,913 (23.3%)
6,245 (3.9%)
514 (3.7%)
N/A
N/A
45,255 (12.7%)
3,427 (13.0%)
-0.01
Lab values- Triglyceride level (mg/dl) (within 6 months); n 
(%)
54,124 (27.5%)
4,074 (32.6%)
8,795 (5.5%)
692 (5.0%)
N/A
N/A
62,919 (17.6%)
4,766 (18.1%)
-0.01
Lab result number- HbA1c (%) mean (only 2 to 20 
included) 
63,912
                                         
4,683
                                            
8,515
                                            
708
                                                
N/A
N/A                                           72,427                                              5,391 
...mean (sd)
7.88 (1.69)
7.88 (1.76)
7.94 (1.76)
7.85 (1.82)
N/A
N/A
7.89 (1.70)
7.88 (1.77)
0.01
...median [IQR]
7.50 [6.80, 8.55]
7.45 [6.60, 8.80]
7.50 [6.80, 8.60]
7.40 [6.50, 8.80]
N/A
N/A
7.50 (1.70)
7.44 (1.77)
0.03
...Missing; n (%)
132,800 (67.5%)
7,802 (62.5%)
151,646 (94.7%)
13,100 (94.9%)
N/A
N/A
284,446 (79.7%)
20,902 (79.5%)
0.00
Lab result number- BNP mean 
1,407
                                            
128
                                                
199
                                                
24
                                                   
N/A
N/A                                              1,606                                                  152 
...mean (sd)
206.69 (379.43)
104.88 (129.95)
374.49 (927.73)
112.61 (201.88)
N/A
N/A
227.48 (482.27)
106.10 (143.82)
0.34
...median [IQR]
91.10 [35.30, 238.60]
48.85 [21.92, 141.45]
83.67 [34.00, 320.00]
27.00 [14.00, 134.95]
N/A
N/A
#VALUE!
#VALUE!
#VALUE!
...Missing; n (%)
195,305 (99.3%)
12,357 (99.0%)
159,962 (99.9%)
13,784 (99.8%)
N/A
N/A
355,267 (99.5%)
26,141 (99.4%)
0.01
Lab result number- BUN (mg/dl) mean 
                                          65,450                                              4,847                                              7,968                                                  784 
N/A
N/A                                           73,418                                              5,631 
...mean (sd)
19.59 (8.55)
18.99 (7.63)
605.16 (9,769.77)
681.77 (10,970.52)
N/A
N/A
83.14 (3218.41)
111.27 (4091.96)
-0.01
...median [IQR]
18.00 [14.00, 23.00]
17.50 [14.00, 22.00]
17.12 [14.00, 22.50]
17.17 [14.00, 22.00]
N/A
N/A
#VALUE!
#VALUE!
#VALUE!
...Missing; n (%)
131,262 (66.7%)
7,638 (61.2%)
152,193 (95.0%)
13,024 (94.3%)
N/A
N/A
283,455 (79.4%)
20,662 (78.6%)
0.02
Lab result number- Creatinine (mg/dl) mean (only 0.1 to 
15 included) 
                                          66,538                                              4,972                                              7,775                                                  746 
N/A
N/A                                           74,313                                              5,718 
...mean (sd)
1.08 (0.41)
1.02 (0.36)
1.06 (0.40)
0.99 (0.30)
N/A
N/A
1.08 (0.41)
1.02 (0.35)
0.16
...median [IQR]
0.99 [0.82, 1.23]
0.95 [0.78, 1.16]
0.99 [0.82, 1.18]
0.93 [0.78, 1.13]
N/A
N/A
0.99 (0.41)
0.95 (0.35)
0.10
...Missing; n (%)
130,174 (66.2%)
7,513 (60.2%)
152,386 (95.1%)
13,062 (94.6%)
N/A
N/A
282,560 (79.2%)
20,575 (78.3%)
0.02
Lab result number- HDL level (mg/dl) mean (only =<5000 
included) 
                                          53,958                                              4,018                                              8,873                                                  695 
N/A
N/A                                           62,831                                              4,713 
...mean (sd)
46.95 (13.91)
46.76 (13.33)
45.59 (47.34)
44.84 (14.34)
N/A
N/A
46.76 (21.97)
46.48 (13.48)
0.02
...median [IQR]
45.00 [37.50, 54.00]
45.00 [37.50, 54.00]
44.00 [36.67, 52.00]
43.50 [36.00, 53.00]
N/A
N/A
44.86 (21.97)
44.78 (13.48)
0.00
...Missing; n (%)
142,754 (72.6%)
8,467 (67.8%)
151,288 (94.5%)
13,113 (95.0%)
N/A
N/A
294,042 (82.4%)
21,580 (82.1%)
0.01
Lab result number- LDL level (mg/dl) mean (only =<5000 
included) 
                                          54,466                                              4,060                                              8,748                                                  635 
N/A
N/A                                           63,214                                              4,695 
...mean (sd)
87.59 (38.87)
83.15 (38.01)
88.66 (40.81)
83.36 (41.13)
N/A
N/A
87.74 (39.14)
83.18 (38.45)
0.12
...median [IQR]
84.00 [63.50, 109.81]
79.50 [60.54, 103.00]
85.00 [64.50, 111.00]
83.00 [62.00, 107.00]
N/A
N/A
84.14 (39.14)
79.97 (38.45)
0.11
...Missing; n (%)
142,246 (72.3%)
8,425 (67.5%)
151,413 (94.5%)
13,173 (95.4%)
N/A
N/A
293,659 (82.3%)
21,598 (82.1%)
0.01
Lab result number- Total cholesterol (mg/dl) mean (only 
=<5000 included) 
                                          54,656                                              4,118                                              8,992                                                  704 
N/A
N/A                                           63,648                                              4,822 
...mean (sd)
172.55 (45.90)
168.99 (44.50)
172.40 (50.33)
171.70 (49.20)
N/A
N/A
172.53 (46.55)
169.39 (45.22)
0.07
...median [IQR]
167.00 [142.00, 197.00]
162.50 [140.00, 192.00]
167.25 [142.00, 198.00]
166.50 [143.00, 198.00]
N/A
N/A
167.04 (46.55)
163.08 (45.22)
0.09
...Missing; n (%)
142,056 (72.2%)
8,367 (67.0%)
151,169 (94.4%)
13,104 (94.9%)
N/A
N/A
293,225 (82.2%)
21,471 (81.7%)
0.01
Table 1: Liraglutide vs 2nd Generation Sulfonylureas

Lab result number- Triglyceride level (mg/dl) mean (only 
=<5000 included) 
                                          54,122                                              4,074                                              8,770                                                  690 
N/A
N/A                                           62,892                                              4,764 
...mean (sd)
177.75 (139.01)
180.45 (141.28)
182.37 (160.30)
188.30 (138.00)
N/A
N/A
178.39 (142.17)
181.59 (140.82)
-0.02
...median [IQR]
148.00 [106.00, 209.00]
150.00 [108.00, 212.00]
148.00 [105.00, 213.00]
153.00 [108.00, 225.12]
N/A
N/A
148.00 (142.17)
150.43 (140.82)
-0.02
...Missing; n (%)
142,590 (72.5%)
8,411 (67.4%)
151,391 (94.5%)
13,118 (95.0%)
N/A
N/A
293,981 (82.4%)
21,529 (81.9%)
0.01
Lab result number- Hemoglobin mean (only >0 included)
                                          46,203                                              3,404                                              5,302                                                  532 
N/A
N/A                                           51,505                                              3,936 
...mean (sd)
13.33 (1.71)
13.48 (1.59)
4,366.28 (194,400.62)
302.76 (6,676.17)
N/A
N/A
461.43 (62368.39)
52.58 (2453.09)
0.01
...median [IQR]
13.40 [12.20, 14.50]
13.50 [12.40, 14.50]
13.50 [12.30, 14.60]
13.50 [12.50, 14.60]
N/A
N/A
#VALUE!
#VALUE!
#VALUE!
...Missing; n (%)
150,509 (76.5%)
9,081 (72.7%)
154,859 (96.7%)
13,276 (96.1%)
N/A
N/A
305,368 (85.6%)
22,357 (85.0%)
0.02
Lab result number- Serum sodium mean (only > 90 and < 
190 included)
                                          64,988                                              4,879                                              7,382                                                  734 
N/A
N/A                                           72,370                                              5,613 
...mean (sd)
139.46 (2.82)
139.80 (2.62)
139.02 (2.67)
139.17 (2.52)
N/A
N/A
139.42 (2.81)
139.72 (2.61)
-0.11
...median [IQR]
140.00 [138.00, 141.00]
140.00 [138.00, 141.50]
139.00 [137.50, 141.00]
139.00 [138.00, 141.00]
N/A
N/A
139.90 (2.81)
139.87 (2.61)
0.01
...Missing; n (%)
131,724 (67.0%)
7,606 (60.9%)
152,779 (95.4%)
13,074 (94.7%)
N/A
N/A
284,503 (79.7%)
20,680 (78.7%)
0.02
Lab result number- Albumin mean (only >0 and <=10 
included)
                                          59,908                                              4,526                                              6,409                                                  689 
N/A
N/A                                           66,317                                              5,215 
...mean (sd)
4.22 (0.33)
4.22 (0.30)
4.14 (0.59)
4.11 (0.62)
N/A
N/A
4.21 (0.36)
4.21 (0.36)
0.00
...median [IQR]
4.23 [4.00, 4.40]
4.20 [4.00, 4.40]
4.20 [4.00, 4.40]
4.20 [4.00, 4.40]
N/A
N/A
4.23 (0.36)
4.20 (0.36)
0.08
...Missing; n (%)
136,804 (69.5%)
7,959 (63.7%)
153,752 (96.0%)
13,119 (95.0%)
N/A
N/A
290,556 (81.4%)
21,078 (80.2%)
0.03
Lab result number- Glucose (fasting or random) mean 
(only 10-1000 included)
                                          64,902                                              4,876                                              7,253                                                  722 
N/A
N/A                                           72,155                                              5,598 
...mean (sd)
165.03 (68.57)
160.65 (68.99)
169.17 (71.16)
163.38 (68.72)
N/A
N/A
165.45 (68.84)
161.00 (68.96)
0.06
...median [IQR]
148.50 [121.00, 189.00]
143.00 [113.00, 186.00]
151.50 [122.00, 195.50]
145.00 [114.38, 191.00]
N/A
N/A
148.80 (68.84)
143.26 (68.96)
0.08
...Missing; n (%)
131,810 (67.0%)
7,609 (60.9%)
152,908 (95.5%)
13,086 (94.8%)
N/A
N/A
284,718 (79.8%)
20,695 (78.7%)
0.03
Lab result number- Potassium mean (only 1-7 included)
                                          66,412                                              4,964                                              7,815                                                  768 
N/A
N/A                                           74,227                                              5,732 
...mean (sd)
4.45 (0.45)
4.45 (0.42)
4.37 (0.45)
4.33 (0.46)
N/A
N/A
4.44 (0.45)
4.43 (0.43)
0.02
...median [IQR]
4.40 [4.17, 4.70]
4.40 [4.20, 4.70]
4.35 [4.05, 4.65]
4.30 [4.00, 4.60]
N/A
N/A
4.39 (0.45)
4.39 (0.43)
0.00
...Missing; n (%)
130,300 (66.2%)
7,521 (60.2%)
152,346 (95.1%)
13,040 (94.4%)
N/A
N/A
282,646 (79.2%)
20,561 (78.2%)
0.02
Comorbidity Scores
CCI (180 days)- ICD9 and ICD10 
...mean (sd)
2.83 (2.07)
2.76 (1.84)
2.22 (1.78)
2.06 (1.51)
3.18 (2.40)
2.91 (2.02)
2.94 (2.24)
2.66 (1.86)
0.14
...median [IQR]
2.00 [1.00, 4.00]
2.00 [1.00, 4.00]
2.00 [1.00, 3.00]
2.00 [1.00, 3.00]
2.00 [1.00, 4.00]
2.00 [1.00, 4.00]
2.00 (2.24)
2.00 (1.86)
0.00
Frailty Score: Qualitative Version 365 days as Categories, 
...0; n (%)
86,571 (44.0%)
6,594 (52.8%)
44,870 (28.0%)
4,399 (31.9%)
158,210 (27.7%)
9,861 (34.6%)
289,651 (31.2%)
20,854 (38.1%)
-0.15
...1 to 2; n (%)
66,596 (33.9%)
3,860 (30.9%)
69,481 (43.4%)
6,189 (44.8%)
191,508 (33.5%)
9,366 (32.9%)
327,585 (35.3%)
19,415 (35.4%)
0.00
...3 or more; n (%)
43,545 (22.1%)
2,031 (16.3%)
45,810 (28.6%)
3,220 (23.3%)
221,750 (38.8%)
9,284 (32.6%)
311,105 (33.5%)
14,535 (26.5%)
0.15
Frailty Score: Empirical Version 365 days as Categories, 
...< 0.12908; n (%)
37,724 (19.2%)
2,178 (17.4%)
25,919 (16.2%)
2,299 (16.6%)
52,677 (9.2%)
2,579 (9.0%)
116,320 (12.5%)
7,056 (12.9%)
-0.01
...0.12908 - 0.1631167; n (%)
63,072 (32.1%)
3,967 (31.8%)
51,002 (31.8%)
4,561 (33.0%)
127,292 (22.3%)
6,775 (23.8%)
241,366 (26.0%)
15,303 (27.9%)
-0.04
...>= 0.1631167; n (%)
95,916 (48.8%)
6,340 (50.8%)
83,240 (52.0%)
6,948 (50.3%)
391,499 (68.5%)
19,157 (67.2%)
570,655 (61.5%)
32,445 (59.2%)
0.05
Non-Frailty; n (%)
111,432 (56.6%)
7,721 (61.8%)
81,246 (50.7%)
7,771 (56.3%)
25,833 (4.5%)
1,177 (4.1%)
218,511 (23.5%)
16,669 (30.4%)
-0.16
Frailty Score (mean): Qualitative Version 365 days, 
...mean (sd)
1.50 (2.05)
1.11 (1.65)
1.90 (2.04)
1.58 (1.65)
2.46 (2.61)
1.97 (2.22)
2.16 (2.41)
1.68 (1.97)
0.22
...median [IQR]
1.00 [0.00, 2.00]
0.00 [0.00, 2.00]
1.00 [0.00, 3.00]
1.00 [0.00, 2.00]
2.00 [0.00, 4.00]
1.00 [0.00, 3.00]
1.62 (2.41)
0.77 (1.97)
0.39
Frailty Score (mean): Empirical Version 365 days, 
...mean (sd)
0.17 (0.06)
0.17 (0.05)
0.17 (0.05)
0.17 (0.05)
0.21 (0.08)
0.20 (0.07)
0.19 (0.07)
0.19 (0.06)
0.00
...median [IQR]
0.16 [0.14, 0.20]
0.16 [0.14, 0.20]
0.16 [0.13, 0.19]
0.16 [0.13, 0.19]
0.19 [0.15, 0.24]
0.19 [0.15, 0.23]
0.18 (0.07)
0.18 (0.06)
0.00
Healthcare Utilization
Any hospitalization; n (%)
22,822 (11.6%)
932 (7.5%)
22,913 (14.3%)
1,089 (7.9%)
94,431 (16.5%)
2,641 (9.3%)
140,166 (15.1%)
4,662 (8.5%)
0.21
Any hospitalization within prior 30 days; n (%)
8,976 (4.6%)
186 (1.5%)
7,999 (5.0%)
174 (1.3%)
34,791 (6.1%)
501 (1.8%)
51,766 (5.6%)
861 (1.6%)
0.22
Any hospitalization during prior 31-180 days; n (%)
15,333 (7.8%)
789 (6.3%)
16,116 (10.1%)
941 (6.8%)
68,046 (11.9%)
2,248 (7.9%)
99,495 (10.7%)
3,978 (7.3%)
0.12
Endocrinologist Visit; n (%)
10,612 (5.4%)
2,709 (21.7%)
9,104 (5.7%)
3,114 (22.6%)
39,543 (6.9%)
7,223 (25.3%)
59,259 (6.4%)
13,046 (23.8%)
-0.50
Endocrinologist Visit (30 days prior); n (%)
5,832 (3.0%)
1,706 (13.7%)
5,126 (3.2%)
2,086 (15.1%)
21,478 (3.8%)
4,455 (15.6%)
32,436 (3.5%)
8,247 (15.0%)
-0.40
Endocrinologist Visit (31 to 180 days prior); n (%)
7,605 (3.9%)
2,033 (16.3%)
6,514 (4.1%)
2,270 (16.4%)
29,932 (5.2%)
5,602 (19.6%)
44,051 (4.7%)
9,905 (18.1%)
-0.43
Internal medicine/family medicine visits; n (%)
174,004 (88.5%)
10,331 (82.7%)
134,865 (84.2%)
11,859 (85.9%)
484,478 (84.8%)
23,819 (83.5%)
793,347 (85.5%)
46,009 (84.0%)
0.04
Internal medicine/family medicine visits (30 days prior) ; 
n (%)
130,177 (66.2%)
7,189 (57.6%)
98,733 (61.6%)
8,352 (60.5%)
347,640 (60.8%)
15,622 (54.8%)
576,550 (62.1%)
31,163 (56.9%)
0.11
Internal medicine/family medicine visits (31 to 180 days 
prior) ; n (%)
153,193 (77.9%)
9,462 (75.8%)
117,762 (73.5%)
10,731 (77.7%)
424,882 (74.3%)
21,819 (76.5%)
695,837 (75.0%)
42,012 (76.7%)
-0.04
Cardiologist visit; n (%)
61,106 (31.1%)
4,345 (34.8%)
46,909 (29.3%)
4,666 (33.8%)
217,811 (38.1%)
10,584 (37.1%)
325,826 (35.1%)
19,595 (35.8%)
-0.01
Number of Cardiologist visits (30 days prior); n (%)
23,285 (11.8%)
1,441 (11.5%)
17,006 (10.6%)
1,545 (11.2%)
81,708 (14.3%)
3,371 (11.8%)
121,999 (13.1%)
6,357 (11.6%)
0.05
Table 1: Liraglutide vs 2nd Generation Sulfonylureas

Number of Cardiologist visits (31 to 180 days prior); n (%)
50,549 (25.7%)
3,740 (30.0%)
39,491 (24.7%)
4,016 (29.1%)
185,317 (32.4%)
9,345 (32.8%)
275,357 (29.7%)
17,101 (31.2%)
-0.03
Electrocardiogram ; n (%)
66,713 (33.9%)
4,279 (34.3%)
58,412 (36.5%)
5,031 (36.4%)
220,597 (38.6%)
10,338 (36.3%)
345,722 (37.2%)
19,648 (35.9%)
0.03
Use of glucose test strips; n (%)
7,094 (3.6%)
514 (4.1%)
5,465 (3.4%)
626 (4.5%)
19,740 (3.5%)
1,110 (3.9%)
32,299 (3.5%)
2,250 (4.1%)
-0.03
Dialysis; n (%)
117 (0.1%)
8 (0.1%)
144 (0.1%)
6 (0.0%)
647 (0.1%)
11 (0.0%)
908 (0.1%)
025 (0.0%)
0.04
Naive new user v8 ; n (%)
59,575 (30.3%)
2,843 (22.8%)
47,064 (29.4%)
2,515 (18.2%)
153,729 (26.9%)
4,885 (17.1%)
260,368 (28.0%)
10,243 (18.7%)
0.22
N antidiabetic drugs at index date  
...mean (sd)
1.67 (0.62)
1.75 (0.72)
1.69 (0.65)
1.77 (0.75)
1.65 (0.62)
1.78 (0.71)
1.66 (0.63)
1.77 (0.72)
-0.16
...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 (0.72)
0.00
number of different/distinct medication prescriptions
...mean (sd)
9.22 (4.44)
11.19 (5.24)
9.31 (4.45)
11.10 (4.95)
9.61 (4.49)
11.07 (4.88)
9.48 (4.47)
11.10 (4.98)
-0.34
...median [IQR]
9.00 [6.00, 12.00]
11.00 [8.00, 14.00]
9.00 [6.00, 12.00]
11.00 [8.00, 14.00]
9.00 [6.00, 12.00]10.00 [8.00, 14.00]
9.00 (4.47)
10.48 (4.98)
-0.31
Number of Hospitalizations
...mean (sd)
0.14 (0.45)
0.09 (0.34)
0.17 (0.46)
0.09 (0.33)
0.23 (0.62)
0.12 (0.41)
0.20 (0.56)
0.11 (0.38)
0.19
...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 (0.56)
0.00 (0.38)
0.00
Number of hospital days
...mean (sd)
0.86 (3.80)
0.45 (2.50)
1.02 (4.23)
0.43 (2.24)
1.61 (5.91)
0.69 (3.22)
1.35 (5.26)
0.57 (2.84)
0.18
...median [IQR]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 (5.26)
0.00 (2.84)
0.00
Number of Emergency Department (ED) visits 
...mean (sd)
0.47 (1.33)
0.40 (1.19)
0.27 (1.64)
0.14 (1.20)
0.69 (1.57)
0.46 (1.22)
0.57 (1.53)
0.37 (1.21)
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, 1.00]
0.00 [0.00, 0.00]
0.00 (1.53)
0.00 (1.21)
0.00
Number of Office visits
...mean (sd)
4.71 (3.74)
5.85 (4.16)
5.01 (4.03)
6.08 (4.35)
5.31 (4.32)
6.61 (4.77)
5.13 (4.15)
6.30 (4.53)
-0.27
...median [IQR]
4.00 [2.00, 6.00]
5.00 [3.00, 8.00]
4.00 [2.00, 7.00]
5.00 [3.00, 8.00]
4.00 [2.00, 7.00]
6.00 [3.00, 9.00]
4.00 (4.15)
5.52 (4.53)
-0.35
Number of Endocrinologist visits
...mean (sd)
0.24 (1.59)
1.18 (3.75)
0.25 (1.57)
1.22 (3.84)
0.38 (2.33)
1.74 (5.44)
0.33 (2.07)
1.48 (4.72)
-0.32
...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 (2.07)
0.00 (4.72)
0.00
Number of internal medicine/family medicine visits
...mean (sd)
10.56 (13.70)
10.28 (14.77)
7.25 (9.99)
7.76 (9.80)
8.78 (11.47)
8.76 (11.54)
8.89 (11.75)
8.85 (11.97)
0.00
...median [IQR]
6.00 [2.00, 14.00]
6.00 [2.00, 13.00]
4.00 [2.00, 9.00]
5.00 [2.00, 10.00]
5.00 [2.00, 12.00] 5.00 [2.00, 12.00]
5.04 (11.75)
5.23 (11.97)
-0.02
Number of Cardiologist visits
...mean (sd)
1.59 (4.13)
1.69 (3.99)
1.34 (3.54)
1.56 (3.83)
2.16 (5.18)
2.04 (5.04)
1.90 (4.72)
1.84 (4.53)
0.01
...median [IQR]
0.00 [0.00, 1.00]
0.00 [0.00, 2.00]
0.00 [0.00, 1.00]
0.00 [0.00, 2.00]
0.00 [0.00, 2.00]
0.00 [0.00, 2.00]
0.00 (4.72)
0.00 (4.53)
0.00
Number electrocardiograms received 
...mean (sd)
0.71 (1.57)
0.67 (1.46)
0.69 (1.33)
0.64 (1.22)
0.86 (1.63)
0.72 (1.36)
0.80 (1.57)
0.69 (1.35)
0.08
...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 (1.57)
0.00 (1.35)
0.00
Number of HbA1c tests ordered
...mean (sd)
1.18 (0.89)
1.37 (0.92)
0.86 (0.89)
1.14 (0.94)
1.27 (0.87)
1.50 (0.88)
1.18 (0.88)
1.38 (0.90)
-0.22
...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 (0.90)
0.00
Number of glucose tests ordered
...mean (sd)
0.47 (2.36)
0.58 (1.39)
0.38 (1.34)
0.49 (1.14)
0.39 (1.02)
0.53 (1.18)
0.41 (1.46)
0.53 (1.22)
-0.09
...median [IQR]
0.00 [0.00, 0.00]
0.00 [0.00, 1.00]
0.00 [0.00, 0.00]
0.00 [0.00, 1.00]
0.00 [0.00, 0.00]
0.00 [0.00, 1.00]
0.00 (1.46)
0.00 (1.22)
0.00
Number of lipid tests ordered
...mean (sd)
0.94 (0.93)
1.08 (1.02)
0.74 (1.19)
1.00 (1.28)
0.93 (0.82)
1.11 (0.90)
0.90 (0.92)
1.08 (1.03)
-0.18
...median [IQR]
1.00 [0.00, 1.00]
1.00 [0.00, 2.00]
0.00 [0.00, 1.00]
1.00 [0.00, 2.00]
1.00 [0.00, 1.00]
1.00 [1.00, 2.00]
0.83 (0.92)
1.00 (1.03)
-0.17
Number of creatinine tests ordered
...mean (sd)
0.07 (0.35)
0.06 (0.32)
0.10 (0.50)
0.07 (0.35)
0.09 (0.42)
0.10 (0.40)
0.09 (0.42)
0.08 (0.37)
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 (0.42)
0.00 (0.37)
0.00
Number of BUN tests ordered
...mean (sd)
0.04 (0.28)
0.03 (0.24)
0.06 (0.37)
0.04 (0.29)
0.06 (0.34)
0.06 (0.30)
0.06 (0.33)
0.05 (0.28)
0.03
...median [IQR]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 (0.33)
0.00 (0.28)
0.00
Number of tests for microalbuminuria
...mean (sd)
0.71 (1.13)
0.85 (1.24)
0.44 (0.90)
0.63 (1.06)
0.41 (0.68)
0.56 (0.78)
0.48 (0.83)
0.64 (0.97)
-0.18
...median [IQR]
0.00 [0.00, 1.00]
0.00 [0.00, 2.00]
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 (0.83)
0.00 (0.97)
0.00
Total N distinct ICD9/ICD10 diagnoses at the 3rd digit 
level 
...mean (sd)
5.56 (7.93)
7.14 (8.40)
2.46 (5.45)
2.45 (4.54)
6.43 (9.60)
6.71 (8.93)
5.56 (8.67)
5.73 (7.92)
-0.02
...median [IQR]
3.00 [0.00, 8.00]
5.00 [0.00, 11.00]
0.00 [0.00, 3.00]
0.00 [0.00, 4.00]
3.00 [0.00, 9.00] 4.00 [0.00, 10.00]
2.48 (8.67)
3.22 (7.92)
-0.09
Use of thiazide; n (%)
27,419 (13.9%)
1,625 (13.0%)
21,582 (13.5%)
1,717 (12.4%)
84,834 (14.8%)
4,198 (14.7%)
133,835 (14.4%)
7,540 (13.8%)
0.02
Use of beta blockers; n (%)
85,663 (43.5%)
5,416 (43.4%)
74,450 (46.5%)
6,002 (43.5%)
283,394 (49.6%)
13,479 (47.3%)
443,507 (47.8%)
24,897 (45.4%)
0.05
Use of calcium channel blockers; n (%)
62,900 (32.0%)
3,589 (28.7%)
50,730 (31.7%)
3,915 (28.4%)
199,227 (34.9%)
8,767 (30.7%)
312,857 (33.7%)
16,271 (29.7%)
0.09
Table 1: Liraglutide vs 2nd Generation Sulfonylureas

Variable
Reference- 2nd 
Generation SUs
Exposure- Liraglutide
Reference- 2nd 
Generation SUs
Exposure- Liraglutide
Reference- 2nd 
Generation SUs
Exposure- Liraglutide
Reference- 2nd 
Generation SUs
Exposure- Liraglutide
St. Diff.
Number of patients
12253
12253
13591
13591
28338
28338                                           54,182                                           54,182 
Age
...mean (sd)
65.57 (7.08)
65.79 (6.77)
62.61 (6.66)
62.89 (6.12)
70.39 (5.17)
70.55 (4.99)
67.35 (6.04)
67.55 (5.73)
-0.03
...median [IQR]
66.00 [61.00, 70.00]
66.00 [61.00, 70.00]
62.00 [60.00, 65.00]
62.00 [60.00, 65.00]
69.00 [66.00, 73.00]
69.00 [67.00, 73.00]
66.57 (6.04)
66.57 (5.73)
0.00
Age categories 
...18 - 54; n (%)
856 (7.0%)
700 (5.7%)
1,433 (10.5%)
1,145 (8.4%)
0 (0.0%)
0 (0.0%)
2,289 (4.2%)
1,845 (3.4%)
0.04
...55 - 64; n (%)
4,440 (36.2%)
4,474 (36.5%)
8,439 (62.1%)
8,448 (62.2%)
876 (3.1%)
682 (2.4%)
13,755 (25.4%)
13,604 (25.1%)
0.01
...65 - 74; n (%)
5,664 (46.2%)
5,858 (47.8%)
2,893 (21.3%)
3,298 (24.3%)
22,136 (78.1%)
22,229 (78.4%)
30,693 (56.6%)
31,385 (57.9%)
-0.03
...>= 75; n (%)
1,293 (10.6%)
1,221 (10.0%)
826 (6.1%)
700 (5.2%)
5,326 (18.8%)
5,427 (19.2%)
7,445 (13.7%)
7,348 (13.6%)
0.00
Gender 
...Males; n (%)
5,550 (45.3%)
5,514 (45.0%)
6,577 (48.4%)
6,643 (48.9%)
11,978 (42.3%)
11,972 (42.2%)
24,105 (44.5%)
24,129 (44.5%)
0.00
...Females; n (%)
6,703 (54.7%)
6,739 (55.0%)
7,014 (51.6%)
6,948 (51.1%)
16,360 (57.7%)
16,366 (57.8%)
30,077 (55.5%)
30,053 (55.5%)
0.00
Race 
...White; n (%)
N/A
N/A
N/A
N/A
24,117 (85.1%)
23,930 (84.4%)
24,117 (85.1%)
23,930 (84.4%)
0.02
...Black; n (%)
N/A
N/A
N/A
N/A
2,464 (8.7%)
2,557 (9.0%)
2,464 (8.7%)
2,557 (9.0%)
-0.01
...Asian; n (%)
N/A
N/A
N/A
N/A
364 (1.3%)
380 (1.3%)
364 (1.3%)
380 (1.3%)
0.00
...Hispanic; n (%)
N/A
N/A
N/A
N/A
481 (1.7%)
511 (1.8%)
481 (1.7%)
511 (1.8%)
-0.01
...North American Native; n (%)
N/A
N/A
N/A
N/A
89 (0.3%)
122 (0.4%)
89 (0.3%)
122 (0.4%)
-0.02
...Other/Unknown; n (%)
N/A
N/A
N/A
N/A
823 (2.9%)
838 (3.0%)
823 (2.9%)
838 (3.0%)
-0.01
Region   (lumping missing&other category with 
West)
...Northeast; n (%)
1,166 (9.5%)
1,177 (9.6%)
2,666 (19.6%)
2,729 (20.1%)
4,555 (16.1%)
4,669 (16.5%)
8,387 (15.5%)
8,575 (15.8%)
-0.01
...South; n (%)
6,705 (54.7%)
6,635 (54.2%)
2,735 (20.1%)
2,766 (20.4%)
13,129 (46.3%)
13,013 (45.9%)
22,569 (41.7%)
22,414 (41.4%)
0.01
...Midwest; n (%)
2,289 (18.7%)
2,291 (18.7%)
6,666 (49.0%)
6,500 (47.8%)
6,131 (21.6%)
6,116 (21.6%)
15,086 (27.8%)
14,907 (27.5%)
0.01
...West; n (%)
2,093 (17.1%)
2,150 (17.5%)
1,372 (10.1%)
1,439 (10.6%)
4,523 (16.0%)
4,540 (16.0%)
7,988 (14.7%)
8,129 (15.0%)
-0.01
...Unknown+missing; n (%)
N/A
N/A
152 (1.1%)
157 (1.2%)
N/A
N/A
152 (1.1%)
157 (1.2%)
-0.01
CV Covariates
Ischemic heart disease; n (%)
3,626 (29.6%)
3,604 (29.4%)
4,206 (30.9%)
4,351 (32.0%)
8,731 (30.8%)
8,831 (31.2%)
16,563 (30.6%)
16,786 (31.0%)
-0.01
Acute MI; n (%)
177 (1.4%)
170 (1.4%)
192 (1.4%)
210 (1.5%)
328 (1.2%)
334 (1.2%)
697 (1.3%)
714 (1.3%)
0.00
ACS/unstable angina; n (%)
234 (1.9%)
254 (2.1%)
271 (2.0%)
281 (2.1%)
511 (1.8%)
477 (1.7%)
1,016 (1.9%)
1,012 (1.9%)
0.00
Old MI; n (%)
485 (4.0%)
479 (3.9%)
279 (2.1%)
288 (2.1%)
1,043 (3.7%)
1,034 (3.6%)
1,807 (3.3%)
1,801 (3.3%)
0.00
Stable angina; n (%)
552 (4.5%)
583 (4.8%)
475 (3.5%)
488 (3.6%)
1,057 (3.7%)
1,123 (4.0%)
2,084 (3.8%)
2,194 (4.0%)
-0.01
Coronary atherosclerosis and other forms of chronic 
ischemic heart disease; n (%)
3,397 (27.7%)
3,383 (27.6%)
3,991 (29.4%)
4,144 (30.5%)
8,336 (29.4%)
8,421 (29.7%)
15,724 (29.0%)
15,948 (29.4%)
-0.01
Other atherosclerosis with ICD10  ; n (%)
111 (0.9%)
119 (1.0%)
139 (1.0%)
155 (1.1%)
443 (1.6%)
470 (1.7%)
693 (1.3%)
744 (1.4%)
-0.01
Previous cardiac procedure (CABG or PTCA or Stent) ; 
n (%)
88 (0.7%)
96 (0.8%)
125 (0.9%)
137 (1.0%)
174 (0.6%)
140 (0.5%)
387 (0.7%)
373 (0.7%)
0.00
History of CABG or PTCA; n (%)
868 (7.1%)
896 (7.3%)
548 (4.0%)
566 (4.2%)
2,354 (8.3%)
2,366 (8.3%)
3,770 (7.0%)
3,828 (7.1%)
0.00
Any stroke; n (%)
925 (7.5%)
891 (7.3%)
958 (7.0%)
1,002 (7.4%)
2,454 (8.7%)
2,433 (8.6%)
4,337 (8.0%)
4,326 (8.0%)
0.00
Ischemic stroke (w and w/o mention of cerebral 
infarction); n (%)
912 (7.4%)
886 (7.2%)
938 (6.9%)
985 (7.2%)
2,437 (8.6%)
2,410 (8.5%)
4,287 (7.9%)
4,281 (7.9%)
0.00
Hemorrhagic stroke; n (%)
19 (0.2%)
16 (0.1%)
27 (0.2%)
27 (0.2%)
38 (0.1%)
45 (0.2%)
084 (0.2%)
088 (0.2%)
0.00
TIA; n (%)
229 (1.9%)
224 (1.8%)
234 (1.7%)
239 (1.8%)
516 (1.8%)
511 (1.8%)
979 (1.8%)
974 (1.8%)
0.00
Other cerebrovascular disease; n (%)
182 (1.5%)
225 (1.8%)
182 (1.3%)
164 (1.2%)
615 (2.2%)
583 (2.1%)
979 (1.8%)
972 (1.8%)
0.00
Late effects of cerebrovascular disease; n (%)
146 (1.2%)
143 (1.2%)
97 (0.7%)
92 (0.7%)
382 (1.3%)
415 (1.5%)
625 (1.2%)
650 (1.2%)
0.00
Cerebrovascular procedure; n (%)
14 (0.1%)
12 (0.1%)
10 (0.1%)
11 (0.1%)
35 (0.1%)
25 (0.1%)
059 (0.1%)
048 (0.1%)
0.00
Heart failure (CHF); n (%)
1,220 (10.0%)
1,238 (10.1%)
978 (7.2%)
976 (7.2%)
3,335 (11.8%)
3,322 (11.7%)
5,533 (10.2%)
5,536 (10.2%)
0.00
Peripheral Vascular Disease (PVD) or PVD Surgery ; n 
(%)
1,032 (8.4%)
1,076 (8.8%)
1,066 (7.8%)
1,057 (7.8%)
2,898 (10.2%)
2,934 (10.4%)
4,996 (9.2%)
5,067 (9.4%)
-0.01
Atrial fibrillation; n (%)
927 (7.6%)
947 (7.7%)
769 (5.7%)
774 (5.7%)
3,069 (10.8%)
3,058 (10.8%)
4,765 (8.8%)
4,779 (8.8%)
0.00
Other cardiac dysrhythmia; n (%)
1,257 (10.3%)
1,284 (10.5%)
896 (6.6%)
925 (6.8%)
3,317 (11.7%)
3,335 (11.8%)
5,470 (10.1%)
5,544 (10.2%)
0.00
Cardiac conduction disorders; n (%)
349 (2.8%)
350 (2.9%)
228 (1.7%)
281 (2.1%)
1,094 (3.9%)
1,069 (3.8%)
1,671 (3.1%)
1,700 (3.1%)
0.00
Other CVD; n (%)
1,446 (11.8%)
1,455 (11.9%)
1,455 (10.7%)
1,447 (10.6%)
4,255 (15.0%)
4,141 (14.6%)
7,156 (13.2%)
7,043 (13.0%)
0.01
Diabetes-related complications
Diabetic retinopathy; n (%)
828 (6.8%)
904 (7.4%)
613 (4.5%)
641 (4.7%)
2,266 (8.0%)
2,359 (8.3%)
3,707 (6.8%)
3,904 (7.2%)
-0.02
Diabetes with other ophthalmic manifestations; n 
(%)
85 (0.7%)
90 (0.7%)
398 (2.9%)
440 (3.2%)
834 (2.9%)
867 (3.1%)
1,317 (2.4%)
1,397 (2.6%)
-0.01
Retinal detachment, vitreous hemorrhage, 
vitrectomy; n (%)
55 (0.4%)
53 (0.4%)
48 (0.4%)
46 (0.3%)
144 (0.5%)
135 (0.5%)
247 (0.5%)
234 (0.4%)
0.01
Retinal laser coagulation therapy; n (%)
70 (0.6%)
71 (0.6%)
82 (0.6%)
91 (0.7%)
190 (0.7%)
199 (0.7%)
342 (0.6%)
361 (0.7%)
-0.01
Occurrence of Diabetic Neuropathy  ; n (%)
2,907 (23.7%)
2,874 (23.5%)
1,852 (13.6%)
1,890 (13.9%)
6,479 (22.9%)
6,619 (23.4%)
11,238 (20.7%)
11,383 (21.0%)
-0.01
 PS-matched
MarketScan
Medicare
POOLED
Optum
Table 1: Liraglutide vs 2nd Generation Sulfonylureas

Occurrence of diabetic nephropathy  with ICD10 ; n 
(%)
2,029 (16.6%)
2,102 (17.2%)
1,042 (7.7%)
1,008 (7.4%)
3,374 (11.9%)
3,490 (12.3%)
6,445 (11.9%)
6,600 (12.2%)
-0.01
Hypoglycemia ; n (%)
267 (2.2%)
271 (2.2%)
369 (2.7%)
400 (2.9%)
866 (3.1%)
840 (3.0%)
1,502 (2.8%)
1,511 (2.8%)
0.00
Hyperglycemia; n (%)
563 (4.6%)
561 (4.6%)
425 (3.1%)
424 (3.1%)
1,251 (4.4%)
1,233 (4.4%)
2,239 (4.1%)
2,218 (4.1%)
0.00
Disorders of fluid electrolyte and acid-base balance; n 
(%)
766 (6.3%)
812 (6.6%)
603 (4.4%)
592 (4.4%)
2,084 (7.4%)
2,147 (7.6%)
3,453 (6.4%)
3,551 (6.6%)
-0.01
Diabetic ketoacidosis; n (%)
16 (0.1%)
14 (0.1%)
19 (0.1%)
15 (0.1%)
31 (0.1%)
32 (0.1%)
066 (0.1%)
061 (0.1%)
0.00
Hyperosmolar hyperglycemic nonketotic syndrome 
(HONK); n (%)
61 (0.5%)
68 (0.6%)
41 (0.3%)
44 (0.3%)
122 (0.4%)
125 (0.4%)
224 (0.4%)
237 (0.4%)
0.00
Diabetes with peripheral circulatory disorders with 
ICD-10  ; n (%)
950 (7.8%)
959 (7.8%)
497 (3.7%)
522 (3.8%)
1,985 (7.0%)
2,021 (7.1%)
3,432 (6.3%)
3,502 (6.5%)
-0.01
Diabetic Foot; n (%)
309 (2.5%)
308 (2.5%)
275 (2.0%)
296 (2.2%)
909 (3.2%)
931 (3.3%)
1,493 (2.8%)
1,535 (2.8%)
0.00
Gangrene ; n (%)
35 (0.3%)
33 (0.3%)
24 (0.2%)
20 (0.1%)
53 (0.2%)
60 (0.2%)
112 (0.2%)
113 (0.2%)
0.00
Lower extremity amputation; n (%)
114 (0.9%)
103 (0.8%)
39 (0.3%)
41 (0.3%)
153 (0.5%)
163 (0.6%)
306 (0.6%)
307 (0.6%)
0.00
Osteomyelitis; n (%)
112 (0.9%)
87 (0.7%)
71 (0.5%)
66 (0.5%)
196 (0.7%)
166 (0.6%)
379 (0.7%)
319 (0.6%)
0.01
Skin infections ; n (%)
693 (5.7%)
714 (5.8%)
788 (5.8%)
794 (5.8%)
2,223 (7.8%)
2,241 (7.9%)
3,704 (6.8%)
3,749 (6.9%)
0.00
Erectile dysfunction; n (%)
353 (2.9%)
350 (2.9%)
307 (2.3%)
312 (2.3%)
833 (2.9%)
821 (2.9%)
1,493 (2.8%)
1,483 (2.7%)
0.01
Diabetes with unspecified complication; n (%)
742 (6.1%)
789 (6.4%)
634 (4.7%)
634 (4.7%)
1,595 (5.6%)
1,646 (5.8%)
2,971 (5.5%)
3,069 (5.7%)
-0.01
Diabetes mellitus without mention of complications; 
n (%)
10,682 (87.2%)
10,639 (86.8%)
12,694 (93.4%)
12,712 (93.5%)
26,299 (92.8%)
26,320 (92.9%)
49,675 (91.7%)
49,671 (91.7%)
0.00
Hypertension: 1 inpatient or 2 outpatient claims 
within 365 days; n (%)
11,668 (95.2%)
11,662 (95.2%)
12,150 (89.4%)
12,086 (88.9%)
27,462 (96.9%)
27,458 (96.9%)
51,280 (94.6%)
51,206 (94.5%)
0.00
Hyperlipidemia ; n (%)
9,662 (78.9%)
9,646 (78.7%)
9,610 (70.7%)
9,643 (71.0%)
23,411 (82.6%)
23,471 (82.8%)
42,683 (78.8%)
42,760 (78.9%)
0.00
Edema; n (%)
1,043 (8.5%)
1,052 (8.6%)
801 (5.9%)
818 (6.0%)
3,069 (10.8%)
3,179 (11.2%)
4,913 (9.1%)
5,049 (9.3%)
-0.01
Renal Dysfunction (non-diabetic) ; n (%)
2,712 (22.1%)
2,829 (23.1%)
1,804 (13.3%)
1,850 (13.6%)
6,163 (21.7%)
6,236 (22.0%)
10,679 (19.7%)
10,915 (20.1%)
-0.01
Occurrence of acute renal disease ; n (%)
378 (3.1%)
362 (3.0%)
199 (1.5%)
212 (1.6%)
922 (3.3%)
902 (3.2%)
1,499 (2.8%)
1,476 (2.7%)
0.01
Occurrence of chronic renal insufficiency; n (%)
2,280 (18.6%)
2,425 (19.8%)
1,368 (10.1%)
1,413 (10.4%)
5,213 (18.4%)
5,351 (18.9%)
8,861 (16.4%)
9,189 (17.0%)
-0.02
Chronic kidney disease ; n (%)
2,222 (18.1%)
2,351 (19.2%)
1,305 (9.6%)
1,356 (10.0%)
4,960 (17.5%)
5,072 (17.9%)
8,487 (15.7%)
8,779 (16.2%)
-0.01
CKD Stage 3-4; n (%)
1,662 (13.6%)
1,694 (13.8%)
967 (7.1%)
1,002 (7.4%)
3,531 (12.5%)
3,647 (12.9%)
6,160 (11.4%)
6,343 (11.7%)
-0.01
Occurrence of hypertensive nephropathy; n (%)
996 (8.1%)
1,051 (8.6%)
517 (3.8%)
517 (3.8%)
2,208 (7.8%)
2,249 (7.9%)
3,721 (6.9%)
3,817 (7.0%)
0.00
Occurrence of miscellaneous renal insufficiency ; n 
(%)
632 (5.2%)
632 (5.2%)
499 (3.7%)
509 (3.7%)
1,836 (6.5%)
1,803 (6.4%)
2,967 (5.5%)
2,944 (5.4%)
0.00
Glaucoma or cataracts ; n (%)
2,530 (20.6%)
2,514 (20.5%)
2,365 (17.4%)
2,305 (17.0%)
7,914 (27.9%)
8,032 (28.3%)
12,809 (23.6%)
12,851 (23.7%)
0.00
Cellulitis or abscess of toe; n (%)
189 (1.5%)
180 (1.5%)
117 (0.9%)
122 (0.9%)
457 (1.6%)
440 (1.6%)
763 (1.4%)
742 (1.4%)
0.00
Foot ulcer; n (%)
301 (2.5%)
290 (2.4%)
274 (2.0%)
296 (2.2%)
894 (3.2%)
912 (3.2%)
1,469 (2.7%)
1,498 (2.8%)
-0.01
Bladder stones; n (%)
17 (0.1%)
8 (0.1%)
15 (0.1%)
14 (0.1%)
43 (0.2%)
41 (0.1%)
075 (0.1%)
063 (0.1%)
0.00
Kidney stones; n (%)
327 (2.7%)
308 (2.5%)
342 (2.5%)
334 (2.5%)
797 (2.8%)
799 (2.8%)
1,466 (2.7%)
1,441 (2.7%)
0.00
Urinary tract infections (UTIs); n (%)
1,051 (8.6%)
1,112 (9.1%)
926 (6.8%)
927 (6.8%)
3,560 (12.6%)
3,636 (12.8%)
5,537 (10.2%)
5,675 (10.5%)
-0.01
Dipstick urinalysis; n (%)
4,584 (37.4%)
4,408 (36.0%)
4,689 (34.5%)
4,477 (32.9%)
11,652 (41.1%)
11,552 (40.8%)
20,925 (38.6%)
20,437 (37.7%)
0.02
Non-dipstick urinalysis; n (%)
5,535 (45.2%)
5,355 (43.7%)
4,803 (35.3%)
4,780 (35.2%)
12,816 (45.2%)
13,035 (46.0%)
23,154 (42.7%)
23,170 (42.8%)
0.00
Urine function test; n (%)
320 (2.6%)
272 (2.2%)
370 (2.7%)
340 (2.5%)
1,106 (3.9%)
974 (3.4%)
1,796 (3.3%)
1,586 (2.9%)
0.02
Cytology; n (%)
92 (0.8%)
84 (0.7%)
127 (0.9%)
113 (0.8%)
315 (1.1%)
286 (1.0%)
534 (1.0%)
483 (0.9%)
0.01
Cystos; n (%)
175 (1.4%)
144 (1.2%)
193 (1.4%)
171 (1.3%)
491 (1.7%)
413 (1.5%)
859 (1.6%)
728 (1.3%)
0.03
Other Covariates
Liver disease; n (%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
000 (0.0%)
000 (0.0%)
#DIV/0!
Osteoarthritis; n (%)
2,500 (20.4%)
2,480 (20.2%)
2,220 (16.3%)
2,172 (16.0%)
7,480 (26.4%)
7,389 (26.1%)
12,200 (22.5%)
12,041 (22.2%)
0.01
Other arthritis, arthropathies and musculoskeletal 
pain; n (%)
5,020 (41.0%)
5,007 (40.9%)
5,094 (37.5%)
5,080 (37.4%)
13,898 (49.0%)
13,833 (48.8%)
24,012 (44.3%)
23,920 (44.1%)
0.00
Dorsopathies; n (%)
3,323 (27.1%)
3,268 (26.7%)
3,062 (22.5%)
3,026 (22.3%)
9,051 (31.9%)
8,893 (31.4%)
15,436 (28.5%)
15,187 (28.0%)
0.01
Fractures; n (%)
348 (2.8%)
360 (2.9%)
347 (2.6%)
346 (2.5%)
1,087 (3.8%)
1,065 (3.8%)
1,782 (3.3%)
1,771 (3.3%)
0.00
Falls ; n (%)
366 (3.0%)
366 (3.0%)
148 (1.1%)
137 (1.0%)
1,009 (3.6%)
967 (3.4%)
1,523 (2.8%)
1,470 (2.7%)
0.01
Osteoporosis; n (%)
558 (4.6%)
551 (4.5%)
422 (3.1%)
421 (3.1%)
1,974 (7.0%)
2,013 (7.1%)
2,954 (5.5%)
2,985 (5.5%)
0.00
Hyperthyroidism; n (%)
126 (1.0%)
98 (0.8%)
103 (0.8%)
68 (0.5%)
339 (1.2%)
285 (1.0%)
568 (1.0%)
451 (0.8%)
0.02
Hypothyroidism ; n (%)
2,366 (19.3%)
2,484 (20.3%)
2,087 (15.4%)
2,028 (14.9%)
4,983 (17.6%)
5,062 (17.9%)
9,436 (17.4%)
9,574 (17.7%)
-0.01
Other disorders of thyroid gland ; n (%)
674 (5.5%)
663 (5.4%)
673 (5.0%)
689 (5.1%)
1,711 (6.0%)
1,749 (6.2%)
3,058 (5.6%)
3,101 (5.7%)
0.00
Depression; n (%)
1,294 (10.6%)
1,297 (10.6%)
1,141 (8.4%)
1,143 (8.4%)
3,570 (12.6%)
3,635 (12.8%)
6,005 (11.1%)
6,075 (11.2%)
0.00
Anxiety; n (%)
1,173 (9.6%)
1,157 (9.4%)
774 (5.7%)
753 (5.5%)
2,518 (8.9%)
2,547 (9.0%)
4,465 (8.2%)
4,457 (8.2%)
0.00
Sleep_Disorder; n (%)
1,217 (9.9%)
1,263 (10.3%)
2,193 (16.1%)
2,170 (16.0%)
4,004 (14.1%)
3,931 (13.9%)
7,414 (13.7%)
7,364 (13.6%)
0.00
Dementia; n (%)
225 (1.8%)
256 (2.1%)
125 (0.9%)
144 (1.1%)
949 (3.3%)
1,006 (3.6%)
1,299 (2.4%)
1,406 (2.6%)
-0.01
Delirium; n (%)
82 (0.7%)
92 (0.8%)
80 (0.6%)
69 (0.5%)
345 (1.2%)
350 (1.2%)
507 (0.9%)
511 (0.9%)
0.00
Psychosis; n (%)
74 (0.6%)
80 (0.7%)
48 (0.4%)
52 (0.4%)
240 (0.8%)
256 (0.9%)
362 (0.7%)
388 (0.7%)
0.00
Obesity; n (%)
4,171 (34.0%)
4,169 (34.0%)
3,000 (22.1%)
2,988 (22.0%)
7,848 (27.7%)
7,815 (27.6%)
15,019 (27.7%)
14,972 (27.6%)
0.00
Overweight; n (%)
509 (4.2%)
525 (4.3%)
281 (2.1%)
264 (1.9%)
804 (2.8%)
818 (2.9%)
1,594 (2.9%)
1,607 (3.0%)
-0.01
Smoking; n (%)
1,387 (11.3%)
1,375 (11.2%)
650 (4.8%)
629 (4.6%)
3,607 (12.7%)
3,542 (12.5%)
5,644 (10.4%)
5,546 (10.2%)
0.01
Alcohol abuse or dependence; n (%)
41 (0.3%)
46 (0.4%)
24 (0.2%)
37 (0.3%)
105 (0.4%)
97 (0.3%)
170 (0.3%)
180 (0.3%)
0.00
Drug abuse or dependence; 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!
COPD; n (%)
1,011 (8.3%)
1,025 (8.4%)
652 (4.8%)
655 (4.8%)
3,311 (11.7%)
3,256 (11.5%)
4,974 (9.2%)
4,936 (9.1%)
0.00
Table 1: Liraglutide vs 2nd Generation Sulfonylureas

Asthma; n (%)
915 (7.5%)
900 (7.3%)
800 (5.9%)
801 (5.9%)
2,455 (8.7%)
2,417 (8.5%)
4,170 (7.7%)
4,118 (7.6%)
0.00
Obstructive sleep apnea; n (%)
2,161 (17.6%)
2,192 (17.9%)
2,342 (17.2%)
2,318 (17.1%)
4,225 (14.9%)
4,227 (14.9%)
8,728 (16.1%)
8,737 (16.1%)
0.00
Pneumonia; n (%)
219 (1.8%)
249 (2.0%)
265 (1.9%)
241 (1.8%)
763 (2.7%)
788 (2.8%)
1,247 (2.3%)
1,278 (2.4%)
-0.01
Imaging; n (%)
8 (0.1%)
15 (0.1%)
8 (0.1%)
10 (0.1%)
37 (0.1%)
34 (0.1%)
53 (0.1%)
59 (0.1%)
0.00
Diabetes Medications
DM Medications - AGIs; n (%)
36 (0.3%)
40 (0.3%)
51 (0.4%)
48 (0.4%)
114 (0.4%)
120 (0.4%)
201 (0.4%)
208 (0.4%)
0.00
DM Medications - Glitazones; n (%)
1,225 (10.0%)
1,202 (9.8%)
1,799 (13.2%)
1,801 (13.3%)
2,672 (9.4%)
2,555 (9.0%)
5,696 (10.5%)
5,558 (10.3%)
0.01
DM Medications - Insulin; n (%)
2,389 (19.5%)
2,476 (20.2%)
2,319 (17.1%)
2,561 (18.8%)
6,609 (23.3%)
6,878 (24.3%)
11,317 (20.9%)
11,915 (22.0%)
-0.03
DM Medications - Meglitinides; n (%)
133 (1.1%)
144 (1.2%)
295 (2.2%)
297 (2.2%)
570 (2.0%)
585 (2.1%)
998 (1.8%)
1,026 (1.9%)
-0.01
DM Medications - Metformin; n (%)
7,287 (59.5%)
7,222 (58.9%)
8,603 (63.3%)
8,476 (62.4%)
17,200 (60.7%)
17,179 (60.6%)
33,090 (61.1%)
32,877 (60.7%)
0.01
Concomitant initiation or current use of SGLT2i; n 
(%)
638 (5.2%)
670 (5.5%)
681 (5.0%)
681 (5.0%)
1,135 (4.0%)
1,182 (4.2%)
2,454 (4.5%)
2,533 (4.7%)
-0.01
Concomitant initiation or current use of AGIs; n (%)
25 (0.2%)
22 (0.2%)
43 (0.3%)
29 (0.2%)
70 (0.2%)
82 (0.3%)
138 (0.3%)
133 (0.2%)
0.02
Concomitant initiation or current use of Glitazones; 
n (%)
916 (7.5%)
864 (7.1%)
1,260 (9.3%)
1,289 (9.5%)
2,006 (7.1%)
1,949 (6.9%)
4,182 (7.7%)
4,102 (7.6%)
0.00
Concomitant initiation or current use of DPP4i ; n 
(%)
109 (0.9%)
109 (0.9%)
130 (1.0%)
124 (0.9%)
217 (0.8%)
225 (0.8%)
456 (0.8%)
458 (0.8%)
0.00
Concomitant initiation or current use of Insulin; n 
(%)
1,423 (11.6%)
1,523 (12.4%)
1,389 (10.2%)
1,588 (11.7%)
4,047 (14.3%)
4,309 (15.2%)
6,859 (12.7%)
7,420 (13.7%)
-0.03
Concomitant initiation or current use of 
Meglitinides; n (%)
72 (0.6%)
84 (0.7%)
170 (1.3%)
207 (1.5%)
392 (1.4%)
398 (1.4%)
634 (1.2%)
689 (1.3%)
-0.01
Concomitant initiation or current use of Metformin; 
n (%)
5,832 (47.6%)
5,784 (47.2%)
6,814 (50.1%)
6,740 (49.6%)
13,754 (48.5%)
13,814 (48.7%)
26,400 (48.7%)
26,338 (48.6%)
0.00
Past use of SGLT2i  ; n (%)
264 (2.2%)
278 (2.3%)
242 (1.8%)
236 (1.7%)
526 (1.9%)
530 (1.9%)
1,032 (1.9%)
1,044 (1.9%)
0.00
Past use of AGIs ; n (%)
11 (0.1%)
18 (0.1%)
8 (0.1%)
19 (0.1%)
44 (0.2%)
38 (0.1%)
063 (0.1%)
075 (0.1%)
0.00
Past use of Glitazones  ; n (%)
309 (2.5%)
338 (2.8%)
539 (4.0%)
512 (3.8%)
666 (2.4%)
606 (2.1%)
1,514 (2.8%)
1,456 (2.7%)
0.01
Past use of DPP4i  ; n (%)
476 (3.9%)
463 (3.8%)
782 (5.8%)
738 (5.4%)
1,389 (4.9%)
1,313 (4.6%)
2,647 (4.9%)
2,514 (4.6%)
0.01
Past use of Insulin  ; n (%)
966 (7.9%)
953 (7.8%)
930 (6.8%)
973 (7.2%)
2,565 (9.1%)
2,569 (9.1%)
4,461 (8.2%)
4,495 (8.3%)
0.00
Past use of Meglitinides  ; n (%)
61 (0.5%)
60 (0.5%)
125 (0.9%)
90 (0.7%)
178 (0.6%)
187 (0.7%)
364 (0.7%)
337 (0.6%)
0.01
Past use of metformin (final)  ; n (%)
1,455 (11.9%)
1,438 (11.7%)
1,789 (13.2%)
1,736 (12.8%)
3,446 (12.2%)
3,365 (11.9%)
6,690 (12.3%)
6,539 (12.1%)
0.01
Other Medications
Use of ACE inhibitors; n (%)
5,063 (41.3%)
5,097 (41.6%)
5,527 (40.7%)
5,554 (40.9%)
11,457 (40.4%)
11,611 (41.0%)
22,047 (40.7%)
22,262 (41.1%)
-0.01
Use of ARBs; n (%)
4,202 (34.3%)
4,160 (34.0%)
5,158 (38.0%)
5,036 (37.1%)
10,227 (36.1%)
10,180 (35.9%)
19,587 (36.2%)
19,376 (35.8%)
0.01
Use of Loop Diuretics ; n (%)
2,037 (16.6%)
2,076 (16.9%)
2,059 (15.1%)
2,080 (15.3%)
6,079 (21.5%)
6,171 (21.8%)
10,175 (18.8%)
10,327 (19.1%)
-0.01
Use of other diuretics; n (%)
501 (4.1%)
516 (4.2%)
565 (4.2%)
591 (4.3%)
1,463 (5.2%)
1,427 (5.0%)
2,529 (4.7%)
2,534 (4.7%)
0.00
Use of nitrates-United; n (%)
852 (7.0%)
864 (7.1%)
907 (6.7%)
968 (7.1%)
2,172 (7.7%)
2,226 (7.9%)
3,931 (7.3%)
4,058 (7.5%)
-0.01
Use of other hypertension drugs; n (%)
871 (7.1%)
875 (7.1%)
900 (6.6%)
899 (6.6%)
2,265 (8.0%)
2,241 (7.9%)
4,036 (7.4%)
4,015 (7.4%)
0.00
Use of digoxin; n (%)
176 (1.4%)
173 (1.4%)
182 (1.3%)
221 (1.6%)
623 (2.2%)
600 (2.1%)
981 (1.8%)
994 (1.8%)
0.00
Use of Anti-arrhythmics; n (%)
207 (1.7%)
203 (1.7%)
222 (1.6%)
224 (1.6%)
668 (2.4%)
636 (2.2%)
1,097 (2.0%)
1,063 (2.0%)
0.00
Use of COPD/asthma meds; n (%)
2,039 (16.6%)
2,073 (16.9%)
2,388 (17.6%)
2,380 (17.5%)
5,744 (20.3%)
5,694 (20.1%)
10,171 (18.8%)
10,147 (18.7%)
0.00
Use of statins; n (%)
8,485 (69.2%)
8,487 (69.3%)
9,378 (69.0%)
9,460 (69.6%)
20,077 (70.8%)
20,155 (71.1%)
37,940 (70.0%)
38,102 (70.3%)
-0.01
Use of other lipid-lowering drugs; n (%)
1,675 (13.7%)
1,649 (13.5%)
2,457 (18.1%)
2,425 (17.8%)
4,125 (14.6%)
4,179 (14.7%)
8,257 (15.2%)
8,253 (15.2%)
0.00
Use of antiplatelet agents; n (%)
1,783 (14.6%)
1,827 (14.9%)
2,483 (18.3%)
2,532 (18.6%)
4,427 (15.6%)
4,465 (15.8%)
8,693 (16.0%)
8,824 (16.3%)
-0.01
Use of oral anticoagulants (Dabigatran, Rivaroxaban, 
Apixaban, Warfarin); n (%)
911 (7.4%)
886 (7.2%)
847 (6.2%)
849 (6.2%)
2,747 (9.7%)
2,722 (9.6%)
4,505 (8.3%)
4,457 (8.2%)
0.00
Use of heparin and other low-molecular weight 
heparins; n (%)
60 (0.5%)
67 (0.5%)
0 (0.0%)
0 (0.0%)
153 (0.5%)
140 (0.5%)
213 (0.4%)
207 (0.4%)
0.00
Use of NSAIDs; n (%)
2,128 (17.4%)
2,143 (17.5%)
2,463 (18.1%)
2,389 (17.6%)
5,307 (18.7%)
5,160 (18.2%)
9,898 (18.3%)
9,692 (17.9%)
0.01
Use of oral corticosteroids; n (%)
2,113 (17.2%)
2,056 (16.8%)
2,208 (16.2%)
2,148 (15.8%)
5,336 (18.8%)
5,278 (18.6%)
9,657 (17.8%)
9,482 (17.5%)
0.01
Use of bisphosphonate (United); n (%)
247 (2.0%)
244 (2.0%)
223 (1.6%)
210 (1.5%)
674 (2.4%)
727 (2.6%)
1,144 (2.1%)
1,181 (2.2%)
-0.01
Use of opioids; n (%)
3,459 (28.2%)
3,463 (28.3%)
3,962 (29.2%)
3,881 (28.6%)
8,527 (30.1%)
8,497 (30.0%)
15,948 (29.4%)
15,841 (29.2%)
0.00
Use of antidepressants; n (%)
3,896 (31.8%)
3,877 (31.6%)
4,178 (30.7%)
4,117 (30.3%)
9,729 (34.3%)
9,631 (34.0%)
17,803 (32.9%)
17,625 (32.5%)
0.01
Use of antipsychotics; n (%)
298 (2.4%)
291 (2.4%)
259 (1.9%)
251 (1.8%)
740 (2.6%)
738 (2.6%)
1,297 (2.4%)
1,280 (2.4%)
0.00
Use of anticonvulsants; n (%)
2,473 (20.2%)
2,503 (20.4%)
2,053 (15.1%)
2,005 (14.8%)
5,861 (20.7%)
5,797 (20.5%)
10,387 (19.2%)
10,305 (19.0%)
0.01
Use of lithium; n (%)
20 (0.2%)
11 (0.1%)
37 (0.3%)
15 (0.1%)
48 (0.2%)
38 (0.1%)
105 (0.2%)
064 (0.1%)
0.03
Use of Benzos; n (%)
1,479 (12.1%)
1,453 (11.9%)
1,788 (13.2%)
1,768 (13.0%)
3,457 (12.2%)
3,377 (11.9%)
6,724 (12.4%)
6,598 (12.2%)
0.01
Use of anxiolytics/hypnotics; n (%)
923 (7.5%)
931 (7.6%)
1,214 (8.9%)
1,203 (8.9%)
2,382 (8.4%)
2,284 (8.1%)
4,519 (8.3%)
4,418 (8.2%)
0.00
Use of dementia meds; n (%)
117 (1.0%)
120 (1.0%)
91 (0.7%)
98 (0.7%)
587 (2.1%)
614 (2.2%)
795 (1.5%)
832 (1.5%)
0.00
Use of antiparkinsonian meds; n (%)
465 (3.8%)
423 (3.5%)
439 (3.2%)
428 (3.1%)
1,225 (4.3%)
1,242 (4.4%)
2,129 (3.9%)
2,093 (3.9%)
0.00
Any use of pramlintide; n (%)
0 (0.0%)
5 (0.0%)
4 (0.0%)
21 (0.2%)
**
**
**
**
**
Any use of 1st generation sulfonylureas; n (%)
1 (0.0%)
0 (0.0%)
8 (0.1%)
1 (0.0%)
**
**
**
**
**
Entresto (sacubitril/valsartan); n (%)
28 (0.2%)
36 (0.3%)
10 (0.1%)
9 (0.1%)
22 (0.1%)
26 (0.1%)
060 (0.1%)
071 (0.1%)
0.00
Initiation as monotherapy  ; n (%)
1,596 (13.0%)
1,798 (14.7%)
1,351 (9.9%)
1,557 (11.5%)
2,855 (10.1%)
2,775 (9.8%)
5,802 (10.7%)
6,130 (11.3%)
-0.02
Labs
                                          25,844                                           25,844 
Lab values- HbA1c (%) ; n (%)
4,749 (38.8%)
4,611 (37.6%)
981 (7.2%)
738 (5.4%)
N/A
N/A
5,730 (22.2%)
5,349 (20.7%)
0.04
Lab values- HbA1c (%) (within 3 months) ; n (%)
3,629 (29.6%)
3,522 (28.7%)
743 (5.5%)
580 (4.3%)
N/A
N/A
4,372 (16.9%)
4,102 (15.9%)
0.03
Lab values- HbA1c (%) (within 6 months) ; n (%)
4,749 (38.8%)
4,611 (37.6%)
981 (7.2%)
738 (5.4%)
N/A
N/A
5,730 (22.2%)
5,349 (20.7%)
0.04
Table 1: Liraglutide vs 2nd Generation Sulfonylureas

Lab values- BNP; n (%)
121 (1.0%)
124 (1.0%)
21 (0.2%)
23 (0.2%)
N/A
N/A
142 (0.5%)
147 (0.6%)
-0.01
Lab values- BNP (within 3 months); n (%)
72 (0.6%)
81 (0.7%)
12 (0.1%)
21 (0.2%)
N/A
N/A
084 (0.3%)
102 (0.4%)
-0.02
Lab values- BNP (within 6 months); n (%)
121 (1.0%)
124 (1.0%)
21 (0.2%)
23 (0.2%)
N/A
N/A
142 (0.5%)
147 (0.6%)
-0.01
Lab values- BUN (mg/dl); n (%)
4,869 (39.7%)
4,746 (38.7%)
902 (6.6%)
766 (5.6%)
N/A
N/A
5,771 (22.3%)
5,512 (21.3%)
0.02
Lab values- BUN (mg/dl) (within 3 months); n (%)
3,694 (30.1%)
3,594 (29.3%)
654 (4.8%)
581 (4.3%)
N/A
N/A
4,348 (16.8%)
4,175 (16.2%)
0.02
Lab values- BUN (mg/dl) (within 6 months); n (%)
4,869 (39.7%)
4,746 (38.7%)
902 (6.6%)
766 (5.6%)
N/A
N/A
5,771 (22.3%)
5,512 (21.3%)
0.02
Lab values- Creatinine (mg/dl) ; n (%)
4,980 (40.6%)
4,900 (40.0%)
955 (7.0%)
797 (5.9%)
N/A
N/A
5,935 (23.0%)
5,697 (22.0%)
0.02
Lab values- Creatinine (mg/dl) (within 3 months) ; n 
(%)
3,790 (30.9%)
3,714 (30.3%)
695 (5.1%)
605 (4.5%)
N/A
N/A
4,485 (17.4%)
4,319 (16.7%)
0.02
Lab values- Creatinine (mg/dl) (within 6 months) ; n 
(%)
4,980 (40.6%)
4,900 (40.0%)
955 (7.0%)
797 (5.9%)
N/A
N/A
5,935 (23.0%)
5,697 (22.0%)
0.02
Lab values- HDL level (mg/dl); n (%)
4,142 (33.8%)
3,943 (32.2%)
903 (6.6%)
681 (5.0%)
N/A
N/A
5,045 (19.5%)
4,624 (17.9%)
0.04
Lab values- HDL level (mg/dl) (within 3 months); n (%)
2,951 (24.1%)
2,818 (23.0%)
630 (4.6%)
508 (3.7%)
N/A
N/A
3,581 (13.9%)
3,326 (12.9%)
0.03
Lab values- HDL level (mg/dl) (within 6 months); n (%)
4,142 (33.8%)
3,943 (32.2%)
903 (6.6%)
681 (5.0%)
N/A
N/A
5,045 (19.5%)
4,624 (17.9%)
0.04
Lab values- LDL level (mg/dl) ; n (%)
4,233 (34.5%)
4,065 (33.2%)
932 (6.9%)
704 (5.2%)
N/A
N/A
5,165 (20.0%)
4,769 (18.5%)
0.04
Lab values- LDL level (mg/dl) (within 3 months) ; n (%)
3,015 (24.6%)
2,914 (23.8%)
648 (4.8%)
520 (3.8%)
N/A
N/A
3,663 (14.2%)
3,434 (13.3%)
0.03
Lab values- LDL level (mg/dl) (within 6 months) ; n (%)
4,233 (34.5%)
4,065 (33.2%)
932 (6.9%)
704 (5.2%)
N/A
N/A
5,165 (20.0%)
4,769 (18.5%)
0.04
Lab values- NT-proBNP; n (%)
10 (0.1%)
30 (0.2%)
1 (0.0%)
3 (0.0%)
N/A
N/A
11 (0.0%)
0 (0.1%)
-
Lab values- NT-proBNP (within 3 months); n (%)
5 (0.0%)
20 (0.2%)
0 (0.0%)
1 (0.0%)
N/A
N/A
05 (0.0%)
0 (0.1%)
-
Lab values- NT-proBNP (within 6 months); n (%)
10 (0.1%)
30 (0.2%)
1 (0.0%)
3 (0.0%)
N/A
N/A
11 (0.0%)
33 (0.1%)
-
Lab values- Total cholesterol (mg/dl) ; n (%)
4,202 (34.3%)
4,042 (33.0%)
911 (6.7%)
691 (5.1%)
N/A
N/A
5,113 (19.8%)
4,733 (18.3%)
0.04
Lab values- Total cholesterol (mg/dl) (within 3 
months) ; n (%)
3,000 (24.5%)
2,889 (23.6%)
634 (4.7%)
517 (3.8%)
N/A
N/A
3,634 (14.1%)
3,406 (13.2%)
0.03
Lab values- Total cholesterol (mg/dl) (within 6 
months) ; n (%)
4,202 (34.3%)
4,042 (33.0%)
911 (6.7%)
691 (5.1%)
N/A
N/A
5,113 (19.8%)
4,733 (18.3%)
0.04
Lab values- Triglyceride level (mg/dl); n (%)
4,168 (34.0%)
3,999 (32.6%)
901 (6.6%)
676 (5.0%)
N/A
N/A
5,069 (19.6%)
4,675 (18.1%)
0.04
Lab values- Triglyceride level (mg/dl) (within 3 
months); n (%)
2,979 (24.3%)
2,862 (23.4%)
629 (4.6%)
503 (3.7%)
N/A
N/A
3,608 (14.0%)
3,365 (13.0%)
0.03
Lab values- Triglyceride level (mg/dl) (within 6 
months); n (%)
4,168 (34.0%)
3,999 (32.6%)
901 (6.6%)
676 (5.0%)
N/A
N/A
5,069 (19.6%)
4,675 (18.1%)
0.04
Lab result number- HbA1c (%) mean (only 2 to 20 
included) 
4,726
                                            
4,589
                                            
877
                                                
694
                                                
N/A
N/A                                              5,603                                              5,283 
...mean (sd)
8.09 (1.82)
7.86 (1.75)
8.13 (1.91)
7.85 (1.83)
N/A
N/A
8.10 (1.83)
7.86 (1.76)
0.13
...median [IQR]
7.70 [6.90, 8.85]
7.40 [6.60, 8.70]
7.60 [6.90, 8.90]
7.40 [6.50, 8.76]
N/A
N/A
7.68 (1.83)
7.40 (1.76)
0.16
...Missing; n (%)
7,527 (61.4%)
7,664 (62.5%)
12,714 (93.5%)
12,897 (94.9%)
N/A
N/A
20,241 (78.3%)
20,561 (79.6%)
-0.03
Lab result number- BNP mean 
121
                                                
124
                                                
21
                                                   
23
                                                   
N/A
N/A                                                  142                                                  147 
...mean (sd)
146.97 (207.33)
105.07 (131.54)
72.61 (105.14)
105.16 (203.02)
N/A
N/A
135.97 (196.72)
105.08 (145.18)
0.18
...median [IQR]
67.00 [20.55, 178.80]
46.65 [21.92, 138.88]
42.00 [10.50, 64.50]
24.00 [14.00, 124.00]
N/A
N/A
#VALUE!
#VALUE!
#VALUE!
...Missing; n (%)
12,132 (99.0%)
12,129 (99.0%)
13,570 (99.8%)
13,568 (99.8%)
N/A
N/A
25,702 (99.5%)
25,697 (99.4%)
0.01
Lab result number- BUN (mg/dl) mean 
                                             4,869                                              4,746                                                  902                                                  766 
N/A
N/A                                              5,771                                              5,512 
...mean (sd)
18.85 (8.25)
18.98 (7.61)
556.53 (9,565.83)
697.32 (11,098.36)
N/A
N/A
102.89 (3780.71)
113.25 (4135.75)
0.00
...median [IQR]
17.00 [13.63, 22.00]
17.50 [14.00, 22.00]
17.00 [14.00, 22.08]
17.00 [14.00, 22.00]
N/A
N/A
#VALUE!
#VALUE!
#VALUE!
...Missing; n (%)
7,384 (60.3%)
7,507 (61.3%)
12,689 (93.4%)
12,825 (94.4%)
N/A
N/A
20,073 (77.7%)
20,332 (78.7%)
-0.02
Lab result number- Creatinine (mg/dl) mean (only 0.1 
to 15 included) 
                                             4,951                                              4,872                                                  855                                                  730 
N/A
N/A                                              5,806                                              5,602 
...mean (sd)
1.04 (0.41)
1.02 (0.36)
1.03 (0.38)
0.99 (0.30)
N/A
N/A
1.04 (0.41)
1.02 (0.35)
0.05
...median [IQR]
0.94 [0.79, 1.17]
0.95 [0.78, 1.16]
0.97 [0.80, 1.15]
0.93 [0.78, 1.13]
N/A
N/A
0.94 (0.41)
0.95 (0.35)
-0.03
...Missing; n (%)
7,302 (59.6%)
7,381 (60.2%)
12,736 (93.7%)
12,861 (94.6%)
N/A
N/A
20,038 (77.5%)
20,242 (78.3%)
-0.02
Lab result number- HDL level (mg/dl) mean (only 
=<5000 included) 
                                             4,142                                              3,943                                                  901                                                  679 
N/A
N/A                                              5,043                                              4,622 
...mean (sd)
46.63 (13.79)
46.80 (13.34)
45.37 (14.04)
44.85 (14.28)
N/A
N/A
46.40 (13.84)
46.51 (13.48)
-0.01
...median [IQR]
44.50 [37.00, 54.00]
45.00 [37.50, 54.00]
44.00 [36.50, 53.00]
43.50 [36.00, 53.00]
N/A
N/A
44.41 (13.84)
44.78 (13.48)
-0.03
...Missing; n (%)
8,111 (66.2%)
8,310 (67.8%)
12,690 (93.4%)
12,912 (95.0%)
N/A
N/A
20,801 (80.5%)
21,222 (82.1%)
-0.04
Lab result number- LDL level (mg/dl) mean (only 
=<5000 included) 
                                             4,143                                              3,983                                                  870                                                  619 
N/A
N/A                                              5,013                                              4,602 
...mean (sd)
87.05 (39.40)
83.22 (37.92)
92.02 (41.04)
83.66 (41.01)
N/A
N/A
87.91 (39.69)
83.28 (38.35)
0.12
...median [IQR]
84.00 [63.00, 109.00]
79.50 [61.00, 103.33]
88.25 [67.00, 115.50]
83.00 [62.00, 107.00]
N/A
N/A
84.74 (39.69)
79.97 (38.35)
0.12
...Missing; n (%)
8,110 (66.2%)
8,270 (67.5%)
12,721 (93.6%)
12,972 (95.4%)
N/A
N/A
20,831 (80.6%)
21,242 (82.2%)
-0.04
Lab result number- Total cholesterol (mg/dl) mean 
(only =<5000 included) 
                                             4,198                                              4,041                                                  909                                                  688 
N/A
N/A                                              5,107                                              4,729 
...mean (sd)
174.87 (45.66)
168.95 (44.31)
177.69 (50.94)
171.56 (49.44)
N/A
N/A
175.37 (46.65)
169.33 (45.10)
0.13
...median [IQR]
169.00 [144.00, 199.00]
162.50 [140.00, 192.00]
173.00 [146.25, 204.00]
166.25 [143.00, 198.00]
N/A
N/A
169.71 (46.65)
163.05 (45.10)
0.15
...Missing; n (%)
8,055 (65.7%)
8,212 (67.0%)
12,682 (93.3%)
12,903 (94.9%)
N/A
N/A
20,737 (80.2%)
21,115 (81.7%)
-0.04
Table 1: Liraglutide vs 2nd Generation Sulfonylureas

Lab result number- Triglyceride level (mg/dl) mean 
(only =<5000 included) 
                                             4,168                                              3,999                                                  899                                                  674 
N/A
N/A                                              5,067                                              4,673 
...mean (sd)
189.65 (149.17)
179.99 (140.90)
191.74 (149.61)
186.92 (137.38)
N/A
N/A
190.02 (149.26)
180.99 (140.41)
0.06
...median [IQR]
155.00 [109.50, 223.00]
150.00 [107.00, 212.00]
157.00 [108.00, 220.50]
152.00 [108.00, 224.00]
N/A
N/A
155.35 (149.26)
150.29 (140.41)
0.03
...Missing; n (%)
8,085 (66.0%)
8,254 (67.4%)
12,692 (93.4%)
12,917 (95.0%)
N/A
N/A
20,777 (80.4%)
21,171 (81.9%)
-0.04
Lab result number- Hemoglobin mean (only >0 
included)
                                             3,487                                              3,344                                                  640                                                  521 
N/A
N/A                                              4,127                                              3,865 
...mean (sd)
13.46 (1.66)
13.48 (1.58)
16,304.65 (395,377.51)
308.91 (6,746.28)
N/A
N/A
2539.84 (155633.49)
53.30 (2475.48)
0.02
...median [IQR]
13.50 [12.40, 14.50]
13.50 [12.40, 14.50]
13.50 [12.40, 14.60]
13.50 [12.50, 14.65]
N/A
N/A
#VALUE!
#VALUE!
#VALUE!
...Missing; n (%)
8,766 (71.5%)
8,909 (72.7%)
12,951 (95.3%)
13,070 (96.2%)
N/A
N/A
21,717 (84.0%)
21,979 (85.0%)
-0.03
Lab result number- Serum sodium mean (only > 90 
and < 190 included)
                                             4,853                                              4,782                                                  895                                                  717 
N/A
N/A                                              5,748                                              5,499 
...mean (sd)
139.54 (2.72)
139.80 (2.62)
139.15 (2.58)
139.15 (2.51)
N/A
N/A
139.48 (2.70)
139.72 (2.61)
-0.09
...median [IQR]
140.00 [138.00, 141.00]
140.00 [138.00, 141.50]
139.00 [137.50, 141.00]
139.00 [137.88, 141.00]
N/A
N/A
139.84 (2.70)
139.87 (2.61)
-0.01
...Missing; n (%)
7,400 (60.4%)
7,471 (61.0%)
12,696 (93.4%)
12,874 (94.7%)
N/A
N/A
20,096 (77.8%)
20,345 (78.7%)
-0.02
Lab result number- Albumin mean (only >0 and <=10 
included)
                                             4,530                                              4,437                                                  788                                                  676 
N/A
N/A                                              5,318                                              5,113 
...mean (sd)
4.23 (0.32)
4.22 (0.30)
4.15 (0.58)
4.11 (0.62)
N/A
N/A
4.22 (0.37)
4.21 (0.36)
0.03
...median [IQR]
4.25 [4.05, 4.43]
4.20 [4.00, 4.40]
4.20 [4.00, 4.40]
4.20 [4.00, 4.40]
N/A
N/A
4.24 (0.37)
4.20 (0.36)
0.11
...Missing; n (%)
7,723 (63.0%)
7,816 (63.8%)
12,803 (94.2%)
12,915 (95.0%)
N/A
N/A
20,526 (79.4%)
20,731 (80.2%)
-0.02
Lab result number- Glucose (fasting or random) mean 
(only 10-1000 included)
                                             4,843                                              4,782                                                  885                                                  704 
N/A
N/A                                              5,728                                              5,486 
...mean (sd)
169.27 (69.50)
160.44 (68.75)
169.76 (71.09)
164.21 (69.10)
N/A
N/A
169.35 (69.75)
160.92 (68.80)
0.12
...median [IQR]
152.00 [123.00, 197.00]
143.00 [113.00, 186.00]
152.00 [122.00, 195.75]
145.25 [115.00, 192.25]
N/A
N/A
152.00 (69.75)
143.29 (68.80)
0.13
...Missing; n (%)
7,410 (60.5%)
7,471 (61.0%)
12,706 (93.5%)
12,887 (94.8%)
N/A
N/A
20,116 (77.8%)
20,358 (78.8%)
-0.02
Lab result number- Potassium mean (only 1-7 
included)
                                             4,941                                              4,865                                                  883                                                  749 
N/A
N/A                                              5,824                                              5,614 
...mean (sd)
4.44 (0.43)
4.44 (0.42)
4.34 (0.44)
4.33 (0.46)
N/A
N/A
4.42 (0.43)
4.43 (0.43)
-0.02
...median [IQR]
4.41 [4.20, 4.70]
4.40 [4.20, 4.70]
4.30 [4.00, 4.70]
4.30 [4.00, 4.60]
N/A
N/A
4.39 (0.43)
4.39 (0.43)
0.00
...Missing; n (%)
7,312 (59.7%)
7,388 (60.3%)
12,708 (93.5%)
12,842 (94.5%)
N/A
N/A
20,020 (77.5%)
20,230 (78.3%)
-0.02
Comorbidity Scores
CCI (180 days)- ICD9 and ICD10 
...mean (sd)
2.71 (1.81)
2.75 (1.84)
2.04 (1.47)
2.05 (1.50)
2.89 (2.02)
2.91 (2.02)
2.64 (1.85)
2.66 (1.86)
-0.01
...median [IQR]
2.00 [1.00, 4.00]
2.00 [1.00, 4.00]
2.00 [1.00, 3.00]
2.00 [1.00, 3.00]
2.00 [1.00, 4.00]
2.00 [1.00, 4.00]
2.00 (1.85)
2.00 (1.86)
0.00
Frailty Score: Qualitative Version 365 days as 
Categories, 
...0; n (%)
6,556 (53.5%)
6,470 (52.8%)
4,392 (32.3%)
4,325 (31.8%)
9,934 (35.1%)
9,809 (34.6%)
20,882 (38.5%)
20,604 (38.0%)
0.01
...1 to 2; n (%)
3,663 (29.9%)
3,793 (31.0%)
5,956 (43.8%)
6,111 (45.0%)
9,080 (32.0%)
9,317 (32.9%)
18,699 (34.5%)
19,221 (35.5%)
-0.02
...3 or more; n (%)
2,034 (16.6%)
1,990 (16.2%)
3,243 (23.9%)
3,155 (23.2%)
9,324 (32.9%)
9,212 (32.5%)
14,601 (26.9%)
14,357 (26.5%)
0.01
Frailty Score: Empirical Version 365 days as 
Categories, 
...< 0.12908; n (%)
2,200 (18.0%)
2,163 (17.7%)
2,347 (17.3%)
2,284 (16.8%)
2,788 (9.8%)
2,572 (9.1%)
7,335 (13.5%)
7,019 (13.0%)
0.01
...0.12908 - 0.1631167; n (%)
4,002 (32.7%)
3,922 (32.0%)
4,497 (33.1%)
4,507 (33.2%)
6,595 (23.3%)
6,757 (23.8%)
15,094 (27.9%)
15,186 (28.0%)
0.00
...>= 0.1631167; n (%)
6,051 (49.4%)
6,168 (50.3%)
6,747 (49.6%)
6,800 (50.0%)
18,955 (66.9%)
19,009 (67.1%)
31,753 (58.6%)
31,977 (59.0%)
-0.01
Non-Frailty; n (%)
7,239 (59.1%)
7,551 (61.6%)
7,578 (55.8%)
7,639 (56.2%)
1,368 (4.8%)
1,168 (4.1%)
16,185 (29.9%)
16,358 (30.2%)
-0.01
Frailty Score (mean): Qualitative Version 365 days, 
...mean (sd)
1.15 (1.76)
1.11 (1.65)
1.60 (1.71)
1.58 (1.64)
1.99 (2.24)
1.97 (2.22)
1.70 (2.01)
1.68 (1.97)
0.01
...median [IQR]
0.00 [0.00, 2.00]
0.00 [0.00, 2.00]
1.00 [0.00, 2.00]
1.00 [0.00, 2.00]
1.00 [0.00, 3.00]
1.00 [0.00, 3.00]
0.77 (2.01)
0.77 (1.97)
0.00
Frailty Score (mean): Empirical Version 365 days, 
...mean (sd)
0.17 (0.05)
0.17 (0.05)
0.16 (0.05)
0.16 (0.05)
0.20 (0.06)
0.20 (0.07)
0.18 (0.06)
0.18 (0.06)
0.00
...median [IQR]
0.16 [0.14, 0.20]
0.16 [0.14, 0.20]
0.16 [0.13, 0.19]
0.16 [0.13, 0.19]
0.19 [0.15, 0.23]
0.18 [0.15, 0.23]
0.18 (0.06)
0.17 (0.06)
0.17
Healthcare Utilization
Any hospitalization; n (%)
941 (7.7%)
916 (7.5%)
1,031 (7.6%)
1,065 (7.8%)
2,631 (9.3%)
2,630 (9.3%)
4,603 (8.5%)
4,611 (8.5%)
0.00
Any hospitalization within prior 30 days; n (%)
162 (1.3%)
186 (1.5%)
158 (1.2%)
171 (1.3%)
509 (1.8%)
500 (1.8%)
829 (1.5%)
857 (1.6%)
-0.01
Any hospitalization during prior 31-180 days; n (%)
802 (6.5%)
773 (6.3%)
898 (6.6%)
919 (6.8%)
2,216 (7.8%)
2,238 (7.9%)
3,916 (7.2%)
3,930 (7.3%)
0.00
Endocrinologist Visit; n (%)
2,262 (18.5%)
2,532 (20.7%)
2,533 (18.6%)
2,934 (21.6%)
6,395 (22.6%)
7,062 (24.9%)
11,190 (20.7%)
12,528 (23.1%)
-0.06
Endocrinologist Visit (30 days prior); n (%)
1,446 (11.8%)
1,557 (12.7%)
1,734 (12.8%)
1,932 (14.2%)
4,097 (14.5%)
4,318 (15.2%)
7,277 (13.4%)
7,807 (14.4%)
-0.03
Endocrinologist Visit (31 to 180 days prior); n (%)
1,786 (14.6%)
1,874 (15.3%)
1,918 (14.1%)
2,110 (15.5%)
5,288 (18.7%)
5,456 (19.3%)
8,992 (16.6%)
9,440 (17.4%)
-0.02
Internal medicine/family medicine visits; n (%)
10,202 (83.3%)
10,147 (82.8%)
11,788 (86.7%)
11,665 (85.8%)
23,822 (84.1%)
23,670 (83.5%)
45,812 (84.6%)
45,482 (83.9%)
0.02
Internal medicine/family medicine visits (30 days 
prior) ; n (%)
7,061 (57.6%)
7,104 (58.0%)
8,414 (61.9%)
8,259 (60.8%)
15,702 (55.4%)
15,549 (54.9%)
31,177 (57.5%)
30,912 (57.1%)
0.01
Internal medicine/family medicine visits (31 to 180 
days prior) ; n (%)
9,245 (75.5%)
9,285 (75.8%)
10,665 (78.5%)
10,541 (77.6%)
21,778 (76.9%)
21,674 (76.5%)
41,688 (76.9%)
41,500 (76.6%)
0.01
Cardiologist visit; n (%)
4,160 (34.0%)
4,220 (34.4%)
4,436 (32.6%)
4,565 (33.6%)
10,443 (36.9%)
10,503 (37.1%)
19,039 (35.1%)
19,288 (35.6%)
-0.01
Number of Cardiologist visits (30 days prior); n (%)
1,419 (11.6%)
1,400 (11.4%)
1,393 (10.2%)
1,516 (11.2%)
3,361 (11.9%)
3,349 (11.8%)
6,173 (11.4%)
6,265 (11.6%)
-0.01
Table 1: Liraglutide vs 2nd Generation Sulfonylureas

Number of Cardiologist visits (31 to 180 days prior); 
n (%)
3,594 (29.3%)
3,630 (29.6%)
3,842 (28.3%)
3,921 (28.8%)
9,261 (32.7%)
9,271 (32.7%)
16,697 (30.8%)
16,822 (31.0%)
0.00
Electrocardiogram ; n (%)
4,252 (34.7%)
4,193 (34.2%)
4,843 (35.6%)
4,951 (36.4%)
10,287 (36.3%)
10,253 (36.2%)
19,382 (35.8%)
19,397 (35.8%)
0.00
Use of glucose test strips; n (%)
500 (4.1%)
503 (4.1%)
623 (4.6%)
615 (4.5%)
1,140 (4.0%)
1,101 (3.9%)
2,263 (4.2%)
2,219 (4.1%)
0.01
Dialysis; n (%)
5 (0.0%)
8 (0.1%)
3 (0.0%)
6 (0.0%)
16 (0.1%)
11 (0.0%)
024 (0.0%)
025 (0.0%)
#DIV/0!
Naive new user v8 ; n (%)
2,783 (22.7%)
2,834 (23.1%)
2,462 (18.1%)
2,509 (18.5%)
4,946 (17.5%)
4,883 (17.2%)
10,191 (18.8%)
10,226 (18.9%)
0.00
N antidiabetic drugs at index date  
...mean (sd)
1.74 (0.70)
1.74 (0.72)
1.78 (0.71)
1.77 (0.74)
1.77 (0.70)
1.77 (0.71)
1.77 (0.70)
1.76 (0.72)
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 (0.70)
2.00 (0.72)
0.00
number of different/distinct medication 
prescriptions
...mean (sd)
11.07 (5.36)
11.08 (5.16)
11.05 (5.23)
11.02 (4.89)
11.05 (5.15)
11.03 (4.85)
11.05 (5.22)
11.04 (4.93)
0.00
...median [IQR]
10.00 [7.00, 14.00]
10.00 [8.00, 14.00]
10.00 [7.00, 14.00]
10.00 [8.00, 14.00]
10.00 [7.00, 14.00]
10.00 [8.00, 14.00]
10.00 (5.22)
10.00 (4.93)
0.00
Number of Hospitalizations
...mean (sd)
0.09 (0.34)
0.09 (0.34)
0.09 (0.32)
0.09 (0.33)
0.12 (0.41)
0.12 (0.41)
0.11 (0.37)
0.11 (0.38)
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 (0.37)
0.00 (0.38)
0.00
Number of hospital days
...mean (sd)
0.45 (2.24)
0.45 (2.52)
0.40 (1.80)
0.43 (2.25)
0.68 (3.01)
0.69 (3.23)
0.56 (2.59)
0.57 (2.86)
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 (2.59)
0.00 (2.86)
0.00
Number of Emergency Department (ED) visits 
...mean (sd)
0.40 (1.08)
0.40 (1.20)
0.14 (1.11)
0.14 (1.17)
0.47 (1.21)
0.46 (1.22)
0.37 (1.16)
0.37 (1.20)
0.00
...median [IQR]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 (1.16)
0.00 (1.20)
0.00
Number of Office visits
...mean (sd)
5.79 (4.49)
5.80 (4.12)
6.02 (5.06)
6.03 (4.31)
6.59 (5.00)
6.58 (4.75)
6.27 (4.90)
6.27 (4.51)
0.00
...median [IQR]
5.00 [3.00, 8.00]
5.00 [3.00, 8.00]
5.00 [3.00, 8.00]
5.00 [3.00, 8.00]
5.00 [3.00, 9.00]
5.00 [3.00, 9.00]
5.00 (4.90)
5.00 (4.51)
0.00
Number of Endocrinologist visits
...mean (sd)
0.98 (3.22)
1.09 (3.58)
0.91 (3.04)
1.15 (3.71)
1.48 (4.78)
1.70 (5.36)
1.22 (4.08)
1.42 (4.62)
-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 (4.08)
0.00 (4.62)
0.00
Number of internal medicine/family medicine visits
...mean (sd)
9.88 (14.15)
10.31 (14.74)
7.49 (9.52)
7.76 (9.83)
8.62 (12.28)
8.76 (11.52)
8.62 (12.12)
8.86 (11.95)
-0.02
...median [IQR]
6.00 [2.00, 13.00]
6.00 [2.00, 13.00]
5.00 [2.00, 10.00]
5.00 [2.00, 10.00]
5.00 [2.00, 11.00]
5.00 [2.00, 12.00]
5.23 (12.12)
5.23 (11.95)
0.00
Number of Cardiologist visits
...mean (sd)
1.76 (4.28)
1.68 (4.00)
1.42 (3.34)
1.55 (3.80)
2.04 (5.01)
2.04 (5.04)
1.82 (4.48)
1.84 (4.53)
0.00
...median [IQR]
0.00 [0.00, 2.00]
0.00 [0.00, 2.00]
0.00 [0.00, 1.00]
0.00 [0.00, 2.00]
0.00 [0.00, 2.00]
0.00 [0.00, 2.00]
0.00 (4.48)
0.00 (4.53)
0.00
Number electrocardiograms received 
...mean (sd)
0.67 (1.35)
0.67 (1.47)
0.64 (1.21)
0.64 (1.22)
0.74 (1.40)
0.72 (1.36)
0.70 (1.34)
0.69 (1.35)
0.01
...median [IQR]
0.00 [0.00, 1.00]
0.00 [0.00, 1.00]
0.00 [0.00, 1.00]
0.00 [0.00, 1.00]
0.00 [0.00, 1.00]
0.00 [0.00, 1.00]
0.00 (1.34)
0.00 (1.35)
0.00
Number of HbA1c tests ordered
...mean (sd)
1.35 (0.92)
1.36 (0.92)
1.13 (0.93)
1.13 (0.93)
1.49 (0.90)
1.49 (0.88)
1.37 (0.91)
1.37 (0.90)
0.00
...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 (0.91)
1.00 (0.90)
0.00
Number of glucose tests ordered
...mean (sd)
0.56 (2.54)
0.57 (1.38)
0.49 (1.40)
0.48 (1.12)
0.52 (1.30)
0.53 (1.17)
0.52 (1.68)
0.53 (1.21)
-0.01
...median [IQR]
0.00 [0.00, 0.00]
0.00 [0.00, 1.00]
0.00 [0.00, 0.00]
0.00 [0.00, 1.00]
0.00 [0.00, 1.00]
0.00 [0.00, 1.00]
0.00 (1.68)
0.00 (1.21)
0.00
Number of lipid tests ordered
...mean (sd)
1.09 (1.01)
1.08 (1.02)
1.00 (1.40)
1.00 (1.28)
1.12 (0.89)
1.11 (0.90)
1.08 (1.07)
1.08 (1.03)
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 (1.07)
1.00 (1.03)
0.00
Number of creatinine tests ordered
...mean (sd)
0.06 (0.33)
0.06 (0.32)
0.07 (0.39)
0.07 (0.36)
0.10 (0.43)
0.10 (0.40)
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)
0.04 (0.25)
0.03 (0.24)
0.04 (0.26)
0.04 (0.29)
0.06 (0.33)
0.06 (0.30)
0.05 (0.30)
0.05 (0.28)
0.00
...median [IQR]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 [0.00, 0.00]
0.00 (0.30)
0.00 (0.28)
0.00
Number of tests for microalbuminuria
...mean (sd)
0.87 (1.24)
0.84 (1.23)
0.63 (1.07)
0.62 (1.06)
0.56 (0.81)
0.56 (0.78)
0.65 (0.99)
0.64 (0.97)
0.01
...median [IQR]
0.00 [0.00, 2.00]
0.00 [0.00, 2.00]
0.00 [0.00, 1.00]
0.00 [0.00, 1.00]
0.00 [0.00, 1.00]
0.00 [0.00, 1.00]
0.00 (0.99)
0.00 (0.97)
0.00
Total N distinct ICD9/ICD10 diagnoses at the 3rd 
digit level 
...mean (sd)
7.11 (8.17)
7.09 (8.36)
2.46 (4.33)
2.42 (4.51)
6.66 (8.69)
6.69 (8.92)
5.71 (7.70)
5.71 (7.91)
0.00
...median [IQR]
5.00 [0.00, 11.00]
5.00 [0.00, 11.00]
0.00 [0.00, 4.00]
0.00 [0.00, 4.00]
4.00 [0.00, 10.00]
4.00 [0.00, 10.00]
3.22 (7.70)
3.22 (7.91)
0.00
Use of thiazide; n (%)
1,601 (13.1%)
1,597 (13.0%)
1,648 (12.1%)
1,695 (12.5%)
4,220 (14.9%)
4,168 (14.7%)
7,469 (13.8%)
7,460 (13.8%)
0.00
Use of beta blockers; n (%)
5,279 (43.1%)
5,288 (43.2%)
5,784 (42.6%)
5,886 (43.3%)
13,340 (47.1%)
13,381 (47.2%)
24,403 (45.0%)
24,555 (45.3%)
-0.01
Use of calcium channel blockers; n (%)
3,483 (28.4%)
3,522 (28.7%)
3,883 (28.6%)
3,851 (28.3%)
8,623 (30.4%)
8,726 (30.8%)
15,989 (29.5%)
16,099 (29.7%)
0.00
Table 1: Liraglutide vs 2nd Generation Sulfonylureas