Results of the REWIND trial presented at the American Diabetes Association 79th Scientific Sessions in San Francisco and simultaneously published in The Lancet demonstrated that the glucagon-like peptide-1 receptor agonist (GLP 1 RA) dulaglutide reduced cardiovascular events by 12%. The study reflects similar benefits seen in other GLP-1 RA trials including LEADER (liraglutide), SUSTAIN-6 (semaglutide), and EXSCEL (long-acting exenatide).
GLP-1 therapies improve glucose control by increasing glucose-dependent insulin secretion, slowing the emptying of the stomach, and reducing postprandial glucagon and food intake.
The REWIND trial included 9,901 patients with type 2 diabetes (T2D) from 24 countries. Participants were randomized 1:1 to receive weekly subcutaneous injections of 1.5 mg dulaglutide (4,949) or placebo (4,952) for up to eight years. At baseline, participants had a mean HbA1c of 7.3% and a mean age of 66.2 years. Participants continued their existing diabetes medications.
Unlike previous GLP-1 RA trials, a high proportion (69%) did not have existing cardiovascular disease. Women comprised 46.3% of the study group.
After a mean follow up of 5.4 years, the primary outcome, a composite of non-fatal myocardial infarction, non-fatal stroke, or death from cardiovascular causes, occurred in 594 participants in the dulaglutide arm and 663 in the placebo arm, for a reduction in risk of 12%.
That result was largely driven by a 24% reduction in the risk of non-fatal stroke. There was no significant reduction in all cause mortality, cardiovascular death or non-fatal myocardial infarction.
Subgroup analysis revealed that participants with and without prior cardiovascular disease derived the same benefit from dulaglutide.
Participants in the dulaglutide arm also experienced modestly greater reduction in HbA1c (0.6%), weight (1.5 kg) and systolic blood pressure (1.7 mm Hg).