Pharmacoepidemiology
Semaglutide versus liraglutide and incidence of diabetes and cardiovascular disease: an analysis of real-world data Ethan Cannon* Ethan Cannon Wendy Wang Faye Norby Rob Walker Pamela Lutsey
Introduction: Semaglutide (2.4 mg) and liraglutide (3.0 mg) are glucagon-like peptide-1 receptor agonists (GLP-1 RAs) initially indicated for treating obesity, though clinical trials have also shown CVD risk reduction and improved glycemic control. While semaglutide is superior for weight loss, no trials have compared these drugs head-to-head for CVD risk, nor assessed incident diabetes as a primary endpoint.
Methods: Using the MarketScan insurance claims database from 2020-22, we matched diabetes-free patients prescribed semaglutide with up to 2 controls prescribed liraglutide by age, sex, enrollment date and prescription date. We used Cox regression to compare semaglutide versus liraglutide use and incident 1) diabetes, 2) hard CVD (myocardial infarction, stroke and heart failure), and 3) a composite of hard CVD plus unstable angina and coronary revascularization. Models adjusted for age, sex and a propensity score determined by comorbidities and use of other medications.
Results: 15,017 semaglutide users and 21,431 matched liraglutide users initiated treatment during 2021 or 2022 (mean age 45; 83% female). Follow-up concluded at the end of 2022 or insurance disenrollment. Over a mean of 0.7 years, there were 631 diabetes, 30 hard CVD, and 64 composite CVD events. Comparing semaglutide with liraglutide, the HR (95% CI) was 0.60 (0.35-1.02) for the composite CVD outcome and 0.57 (0.26-1.25) for hard CVD. The proportional hazards assumption was violated in the analysis of diabetes (p=.01); semaglutide was associated with higher risk in the first six months of follow-up (2.07 [1.70-2.53]) and lower risk thereafter (0.70 [0.54-0.92]).
Conclusions: In this real-world study of GLP-1 RAs, results directionally favored semaglutide for CVD outcomes. For diabetes, the change in directionality may be supported by the SUSTAIN 10 and PIONEER 4 trials, where liraglutide initially had a greater effect on glycemic control but semaglutide was superior at completion of the study.