CV Benefit of Dulaglutide Present Regardless of Background Metformin Use

A new analysis of data from the REWIND trial indicate dulaglutide (Trulicity) is cardioprotective in patients with diabetes and established or at high risk for coronary vascular disease regardless of background metformin use.

Results of the study, which were presented at European Society of Cardiology (ESC) Congress 2020, found the cardiovascular benefit seen with the GLP-1 receptor agonist in the REWIND trial—putting to rest any speculation the effects seen in the trial were a result of background metformin therapy.

“The present data favor the hypothesis that the cardiovascular benefit of the GLP-1 receptor agonist dulaglutide is consistent regardless of baseline metformin therapy in a population of patients with type 2 diabetes mellitus with established cardiovascular disease or at high cardiovascular risk,” said Giulia Ferrannini, of the Department of Medical Sciences at the University of Turin in Italy, during her presentation at ESC Congress 2020.

After the 2019 ESC/European Association for the Study of Diabetes (EASD) European Guidelines for Diabetes, Prediabetes and Coronary Artery Disease, some clinicians began to speculate whether the recommendation of GLP-1 receptor agonists as an initial glucose-lowering therapy was warranted. To create a more clear determination of whether the cardioprotective effects seen with GLP-1 receptor agonists in clinical trials is the result of metformin therapy, investigators designed the current study as a subgroup analysis of the REWIND trial.

The multicenter, double-blind, placebo-controlled REWIND trial included patients with type 2 diabetes and either a previous cardiovascular event or at high risk for a cardiovascular event. These patients were randomized in a 1:1 to subcutaneous dulaglutide or placebo. With a primary outcome of the first of a composite of non-fatal myocardial infarction, stroke, or cardiovascular death, results of the trial provided investigators data related to a cohort of more than 9500 patients.

From this patient population, investigators identified a cohort of 1864 patients without metformin use at baseline. Investigators noted patients not using metformin at baseline were older, leaner, more likely to be women, and have a history of prior cardiovascular events, heart failure, and renal disease than their counterparts who were taking metformin at baseline.

During a follow-up period lasting a median of 5.4 years, at the primary outcome of the study occurred in 12% of patients receiving baseline metformin and in 215% of patients not receiving metformin at baseline. Results of the investigators’ analysis indicated no significant difference in the effect of dulaglutide on the primary outcome in the groups with and without background metformin use at baseline (HR, 0.93; 95% CI, 0.82-1.06 vs HR, 0.78; 95% CI, 0.61-0.99; P for interaction=.16).

Investigators also assessed the effects of dulaglutide with and without metformin on the secondary outcomes of the trial, which included a microvascular composite end point, all-cause death, and heart failure. In this analysis, investigators found the effects of dulaglutide on the secondary outcomes was not modified by baseline metformin use (P interaction for all >.1).

This study, “Dulaglutide is cardioprotective with or without background metformin in patients with diabetes and established or high risk for coronary vascular disease. A subgroup analysis of the REWIND Trial,” was presented at ESC Congress 2020.