Cardiometabolic & kidneyCohort study
Comparative Cardiovascular Effectiveness of Glucagon-Like Peptide 1 Receptor Agonists and Sodium-Glucose Cotransporter 2 Inhibitors in Diabetes Mellitus
- Retrospective cohort study
- multinational
- new-user active-comparator
- 10 claims and EHR databases
- propensity score adjustment
- negative control calibration
- random-effects meta-analysis across data sources
Diagnostics confirmed adequate equipoise, covariate balance and power to detect similarity in HRs between 0.8 and 1.2 for commonly used agents
Authors' conclusion
In this large-scale real-world study, individual GLP-1RAs and SGLT2Is exhibited largely comparable cardiovascular benefits, including in patients with established CVD.
Study context
- Population
- Adults with T2DM on metformin initiating second-line therapy with 1 of 6 GLP-1RAs or 1 of 4 SGLT2Is316,242 with established CVD
- Participants
- 1,245,211 adults
- Exposure
- Individual GLP-1RAs vs individual SGLT2Is
- Empagliflozinn = 393,499reference
- Semaglutiden = 235,585
- Dapagliflozinn = 208,666
- Dulaglutiden = 207,348
- Outcome
- 3-point MACE (acute MI, stroke, sudden cardiac death) and 4-point MACE (adding hospitalization/ED visit with HF)
Main finding
As reported in the abstract
3-point and 4-point MACE
Semaglutide vs EmpagliflozinMeta-analytic HR (95% CI)
3-point MACE
1.05(0.79–1.39)
4-point MACE
0.95(0.81–1.12)
Observational data: associations, not effects.
Secondary outcomes
3-point and 4-point MACE, established CVD (subgroup)
- Consistent findings in the CVD subgroup
Original publication
Comparative Cardiovascular Effectiveness of Glucagon-Like Peptide 1 Receptor Agonists and Sodium-Glucose Cotransporter 2 Inhibitors in Diabetes Mellitus. J Am Coll Cardiol. Published 15 April 2026. doi:10.1016/j.jacc.2026.02.5123
Summarised from the published abstract; every number is checked against it