Semaglutide <i>vs</i> . liraglutide and incidence of diabetes and cardiovascular disease: A target trial emulation using real‐world data

AIMS: The glucagon-like peptide-1 receptor agonists (GLP-1 RAs) semaglutide and liraglutide are approved for chronic weight management. Both drugs also have favourable effects on the risk of developing diabetes and cardiovascular disease (CVD) compared with placebo, but their comparative effectiveness for these outcomes is unclear. METHODS: We employed an active comparator, new user design to emulate a target trial using data from MarketScan claims databases. Enrolees free of diabetes and CVD prescribed semaglutide or liraglutide during 2021-2023 were matched 1:1. Primary endpoints included incident diabetes and CVD (myocardial infarction, heart failure or stroke). We used Cox regression adjusted for a propensity score reflective of comorbidities and medication use. RESULTS: We matched 57 456 GLP-1 RA users (mean age 45; 83% female). Over 1-year mean follow-up, we observed 1104 diabetes events and 57 CVD events. After regression adjustment, semaglutide users had 12% lower risk of diabetes (hazard ratio [HR]: 0.88; 95% CI: 0.78, 0.99). For this endpoint, the proportional hazards assumption was violated (p < .0001), so results were stratified by follow-up time. During the first 6 months of follow-up, semaglutide use was not associated with risk of diabetes compared with liraglutide use (HR: 0.99 [0.82-1.18]), but a significant association was present thereafter (HR: 0.80 [0.68, 0.94]). We did not detect a difference in risk of CVD events (HR: 1.25 [0.74-2.11]). CONCLUSIONS: In this real-world study, semaglutide users had lower risk of incident diabetes compared with liraglutide users. Additional research is needed to elucidate comparative effectiveness of these drugs for cardiovascular risk.