Comparative effectiveness of GLP-1 receptor agonists on cardiovascular outcomes among adults with type 2 diabetes and moderate cardiovascular risk: emulation of a target trial.

AIM: To compare the cardiovascular outcomes of glucagon-like peptide-1 receptor agonists (GLP-1RAs) among adults with type 2 diabetes mellitus (T2D) at moderate cardiovascular risk.

METHODS

We emulated a target trial using claims data of adults with T2D at moderate cardiovascular risk who initiated dulaglutide, exenatide, liraglutide, or semaglutide between 01/01/2014-12/31/2021. Random treatment assignment was emulated by propensity scores and incorporated into inverse probability of treatment weighted (IPTW) Cox models. Outcomes were time to composite major adverse cardiovascular events (MACE: myocardial infarction, stroke, and all-cause mortality), expanded MACE (MACE, hospitalization for heart failure, and revascularization) and its components, and severe hypoglycemia.

RESULTS

After IPTW, 35,572 patients initiated dulaglutide, 4376 initiated exenatide, 8843 initiated liraglutide, and 33,063 initiated semaglutide. Compared to dulaglutide, semaglutide was associated with lower risk of MACE (HR 0.85, 95CI % 0.78-0.93), expanded MACE (HR 0.92, 95CI % 0.87-0.96), all-cause mortality (HR 0.81, 95CI % 0.71-0.92), stroke (HR 0.82, 95CI % 0.70-0.97), and revascularization (HR 0.93, 95CI % 0.88-0.99), while liraglutide was associated with lower risk of MACE (HR 0.84, 95CI % 0.72-0.97) and all-cause mortality (HR 0.79, 95CI % 0.64-0.99).

CONCLUSIONS

Among GLP-1RAs, semaglutide and liraglutide were associated with the greatest cardiovascular risk reduction in patients with T2D at moderate cardiovascular risk.