Semaglutide vs. liraglutide and incidence of diabetes and cardiovascular disease: A target trial emulation using real‐world data
7 affiliations
- 1Division of Epidemiology & Community Health University of Minnesota School of Public Health Minneapolis Minnesota USA
- 2Department of Epidemiology, Peter O'Donnell Jr. School of Public Health UT Southwestern Medical Center Dallas Texas USA
- 3Department of Internal Medicine UT Southwestern Medical Center Dallas Texas USA
- 4Department of Tropical Medicine and Infectious Diseases Tulane University Celia Weatherhead School of Public Health New Orleans Louisiana USA
- 5Department of Epidemiology Tulane University Celia Weatherhead School of Public Health New Orleans Louisiana USA
- 6Division of Diabetes, Endocrinology and Metabolism, Department of Medicine University of Minnesota Medical School Minneapolis Minnesota USA
- 7Department of Pharmaceutical Care & Health Systems University of Minnesota College of Pharmacy Minneapolis Minnesota USA
Abstract
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.
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BibTeX
@article{cannon2026semaglutide,
title = {{Semaglutide vs. liraglutide and incidence of diabetes and cardiovascular disease: A target trial emulation using real‐world data}},
author = {Ethan J. Cannon and Wendy Wang and Faye L. Norby and Rob F. Walker and Shalini Kulasingam and Lisa S. Chow and Joel F. Farley and Pamela L. Lutsey},
journal = {British Journal of Clinical Pharmacology},
year = {2026},
month = jul,
doi = {10.1002/bcp.70711},
url = {https://doi.org/10.1002/bcp.70711},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Semaglutide vs. liraglutide and incidence of diabetes and cardiovascular disease: A target trial emulation using real‐world data
AU - Ethan J. Cannon
AU - Wendy Wang
AU - Faye L. Norby
AU - Rob F. Walker
AU - Shalini Kulasingam
AU - Lisa S. Chow
AU - Joel F. Farley
AU - Pamela L. Lutsey
PY - 2026
DA - 2026/07/16
JO - British Journal of Clinical Pharmacology
DO - 10.1002/bcp.70711
UR - https://doi.org/10.1002/bcp.70711
AB - 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.
SN - 0306-5251
SN - 1365-2125
ER -