Cardiovascular outcomes with glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes: a meta-analysis

Abstract

Amylin Pharmaceuticals (AstraZeneca).

The Clinical Impact of GLP-1 Receptor Agonists in Type 2 Diabetes: Focus on the Long-Acting Analogs

“…61 A meta-analysis of the four cardiovascular trials reported to date evaluating cardiovascular safety of the GLP-1 RA included ELIXA, LEADER, SUSTAIN-6, and EXSCEL. 62 These trials demonstrated cardiovascular safety, with findings from two trials (LEADER and SUSTAIN-6) showing significant reductions in the primary endpoint, a 3-point MACE outcome, including cardiovascular mortality, nonfatal myocardial infarction, or nonfatal stroke. Only liraglutide was associated with significant reductions in all-cause mortality and cardiovascular mortality, and only semaglutide was associated with a significant reduction in nonfatal stroke.…”

“…If one assumes that all of the GLP-1 RAs were to show a class effect for cardioprotection and average the results of the LEADER, ELIXA, SUSTAIN-6, and EXSCEL studies, then the HR would be 0.90. 62 …”

The Ascending GLP-1 Road From Clinical Safety to Reduction of Cardiovascular Complications

“…Multiple cardiovascular outcome trials (CVOTs) have been carried out examining the safety of GLP-1R agonists in individuals with T2D and existing cardiovascular disease (CVD) or multiple CVD risk factors. Individual studies to date revealed cardiovascular safety (18), a trend toward reduction in major cardiovascular events (19), or a clear reduction in major adverse cardiovascular events (MACE) such as stroke (20) and cardiovascular death (6,21). Indeed, a meta-analysis of the major CVOTs was consistent with the notion that the GLP-1R agonists class reduces MACE, cardiovascular mortality, and risk for all-cause mortality (6).…”

Sodium Glucose Cotransporter 2 Inhibitors and Amputation Risk

“…Recently, findings from clinical trials of 2 classes of glucose-lowering agents (eg, sodium glucose cotransporter 2 inhibitors [SGLT2i] and glucagon-like peptide-1 receptor agonists) have demonstrated cardiovascular benefits with patterns and timing of efficacy that suggest mediation through mechanisms apart from glucose lowering alone. [2][3][4] The SGLT2i appear to have particularly profound benefits in patients with established cardiovascular disease for reducing cardiovascular death and heart failure as well as adverse renal outcomes. Benefits have been reported in 2 completed randomized trials with consistent associations in observational studies, [2][3][4][5] including those reported by Udell et al 6 in this issue of Circulation.…”

“…[2][3][4] The SGLT2i appear to have particularly profound benefits in patients with established cardiovascular disease for reducing cardiovascular death and heart failure as well as adverse renal outcomes. Benefits have been reported in 2 completed randomized trials with consistent associations in observational studies, [2][3][4][5] including those reported by Udell et al 6 in this issue of Circulation. In contrast to the more consistent cardiovascular benefits described across these studies, however, is a finding isolated to the CANVAS trial (Canagliflozin Cardiovascular Assessment Study) showing an excess risk of amputation with canagliflozin.…”