Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial

The REWIND trial (Researching Cardiovascular Events with a Weekly INcretin in Diabetes) was one of the largest and longest cardiovascular outcome studies with GLP-1 agonists, enrolling 9,901 patients with type 2 diabetes and cardiovascular risk factors (or established cardiovascular disease) from 24 countries, with a median follow-up of 5.4 years.

Participants were randomized to receive dulaglutide 1.5 mg subcutaneous weekly or placebo. The primary composite endpoint (MACE) included cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Dulaglutide significantly reduced MACE by 12% (hazard ratio 0.88; 95% CI 0.79–0.99; p=0.026). Notably, the reduction in non-fatal stroke was 24% (HR 0.76).

A key differentiator of REWIND compared to prior GLP-1 cardiovascular outcome studies is that 69% of participants did not have established cardiovascular disease at baseline, demonstrating benefit in both primary and secondary prevention. The population also included a higher proportion of women (46%) and was more geographically diverse.

The REWIND findings consolidated the position of GLP-1 agonists as agents with proven cardiovascular benefit in type 2 diabetes, influencing international guidelines that began recommending these medications earlier in patients with elevated cardiovascular risk.