GLP-1 RA, with or without SGLT2 inhibitors, prevents cardiac events in T2D

Treatment with the glucagon-like peptide-1 receptor agonist (GLP-1 RA) albiglutide results in fewer cardiovascular events, irrespective of sodium-glucose cotransporter-2 (SGLT2) inhibitor use, among patients with type 2 diabetes (T2D) and cardiovascular disease, according to the post hoc analysis of Harmony Outcomes*.

A total of 9,462 participants were assessed, of whom 575 (6.1 percent) received SGLT2 inhibitors at baseline. Albiglutide reduced the composite of cardiovascular death, myocardial infarction, or stroke (major adverse cardiovascular events) with or without the use of SGLT2 inhibitors (p_interaction=0.70).

Additionally, SGLT2 inhibitors did not modify the effect of albiglutide on secondary outcomes and adverse events.

In the meta-analysis of Harmony Outcomes and AMPLITUDE-O**, 13,538 patients were included, of whom 1,193 (8.8 percent) used SGLT2 inhibitors.

GLP-1 RAs, compared with placebo, decreased major adverse cardiovascular events independently of SGLT2 inhibitor use (with SGLT2 inhibitor: hazard ratio [HR], 0.78, 95 percent confidence interval [CI], 0.49‒1.24; without SGLT2 inhibitor: HR, 0.77, 95 percent CI, 0.6‒0.87; p_interaction=0.95) and reduced heart failure hospitalization (HR, 0.72, 95 percent CI, 0.55‒0.92 vs HR, 0.34, 95 percent CI, 0.12‒0.96; p_interaction=0.18).

“These findings suggest that the combination of GLP-1 RAs with SGLT2 inhibitors may further reduce cardiovascular risk,” the authors said. “Clinical trials with combination therapy are needed.”

In this study, a post hoc analysis of Harmony Outcomes was conducted to assess the effect of albiglutide in T2D with cardiovascular disease by background SGLT2 inhibitor use. The authors also performed a trial-level meta-analysis of Harmony Outcomes and AMPLITUDE-O, which examined T2D with cardiovascular or renal disease, combining the treatment effect estimates based on SGLT2 inhibitor use.

*Albiglutide and Cardiovascular Outcomes in Patients With Type 2 Diabetes and Cardiovascular Disease

**Effect of Efpeglenatide on Cardiovascular Outcomes