Dulaglutide, a glucagon-like peptide 1 receptor agonist (GLP-1 RA), significantly reduced major adverse cardiovascular events (MACE), a composite endpoint of cardiovascular (CV) death, non-fatal myocardial infarction (MI) or non-fatal stroke, meeting the primary efficacy objective in the Researching cardiovascular Events with a Weekly INcretin in Diabetes (REWIND) trial (n=9,901). Once-weekly dulaglutide is the first type 2 diabetes (T2DM) medicine to demonstrate superiority in the reduction of MACE in a clinical trial that included a majority of participants who did not have established CV disease (CVD).

REWIND is distinct compared to other CV outcome trials due to the limited number of people with established CVD who participated in the trial, allowing dulaglutide’s CV effect to be measured in a broad population of people with T2DM. Importantly, REWIND had a median follow-up period of more than 5 years, the longest for a CV outcome trial in the GLP-1 RA class. In comparison, other CV outcome trials had more people with a higher baseline HbA1C and a greater percentage of patients who had established CVD. Of the 9,901 REWIND participants, the mean baseline HbA1C was relatively lower at 7.3%, and only 31% had established CVD.

REWIND was a multicenter, randomized, double-blind, placebo-controlled trial designed to assess the effect of dulaglutide 1.5 mg, compared to placebo, both added to standard of care, on CV events in adults with T2DM. The primary CV outcome was the first occurrence of MACE. Secondary outcomes include each component of the primary composite CV outcome, a composite clinical microvascular outcome comprising retinal or renal disease, hospitalization for unstable angina, heart failure (HF) requiring hospitalization or an urgent HF visit, and all-cause mortality. Prior (or established) CVD in REWIND was defined as prior MI, prior ischemic stroke, prior unstable angina, prior revascularization (coronary, carotid, or peripheral), prior hospitalization for ischemia-related events (unstable angina or myocardial ischemia on imaging, or need for percutaneous coronary intervention), or prior documented myocardial ischemia.

The REWIND trial's international scope, high proportion of women, high proportion of people without established CVD and inclusion of participants with a lower mean baseline hbA1C suggest that the findings will be directly relevant to the typical T2DM patient seen in general practice throughout the world.

The safety profile of dulaglutide in REWIND was generally consistent with the GLP-1 RA class. Detailed results will be presented at the American Diabetes Association (ADA) Scientific Sessions in 2019.

Source: press release Eli Lilly, Nov 5, 2018