Are there long-term studies on GLP-1 (Glucagon-Like Peptide-1) agonists?

From the Guidelines

Long-term Studies on GLP-1 Agonists

Yes, there are long-term studies on GLP-1 agonists, which have demonstrated their efficacy in reducing cardiovascular events in patients with type 2 diabetes.

• The LEADER trial 1, a randomized, double-blind trial, assessed the effect of liraglutide, a GLP-1 receptor agonist, versus placebo on cardiovascular outcomes in 9,340 people with type 2 diabetes at high risk for cardiovascular disease or with cardiovascular disease.
• The trial showed that the primary composite outcome (MI, stroke, or cardiovascular death) occurred in fewer participants in the treatment group (13.0%) than in the placebo group (14.9%) (HR 0.87 [95% CI 0.78–0.97]; P < 0.001 for noninferiority; P = 0.01 for superiority).
• Semaglutide, another GLP-1 receptor agonist, has also been studied in the SUSTAIN-6 trial 1, which demonstrated a significant reduction in cardiovascular events compared to placebo.
• Other GLP-1 receptor agonists, such as albiglutide and dulaglutide, have also shown reductions in cardiovascular events in clinical trials 1.
• The evidence suggests that GLP-1 receptor agonists, as a class, reduce the risk of atherosclerotic major adverse cardiovascular events to a comparable extent as SGLT2 inhibitors 1.
• The LEADER trial 1 and other studies provide strong evidence for the long-term benefits of GLP-1 agonists in reducing cardiovascular risk in patients with type 2 diabetes.
• The use of GLP-1 agonists, such as liraglutide and semaglutide, is supported by the evidence as a valuable treatment option for patients with type 2 diabetes at high risk for cardiovascular disease.

From the Research

Long-term Studies on GLP-1 Agonists

• There are several long-term studies on GLP-1 agonists, including a systematic review and meta-analysis of randomized controlled trials that evaluated the effects of GLP-1 receptor agonists on cardiovascular outcomes in high-risk patients with type 2 diabetes mellitus (T2DM) 2.
• Another systematic review assessed the long-term cardiovascular effects of GLP-1 receptor agonists in adults with T2D, comparing them to placebo, standard care, or other glucose-lowering medications 3.
• A nationwide cohort study investigated the association between long-term prognosis and GLP-1RA treatment before ST-segment elevation myocardial infarction (STEMI) in patients with type 2 diabetes, finding that GLP-1RA treatment was associated with lower long-term mortality 4.
• A review of glycemic benefits and beyond highlighted the potential of GLP-1 receptor agonists in improving glycemic control, as well as their effects on weight, blood pressure, cholesterol, renal function, and beta-cell proliferation 5.
• A global retrospective cohort study examined the long-term safety and efficacy of GLP-1 receptor agonists in individuals with obesity and without type 2 diabetes, finding that GLP-1 RA treatment was associated with a lower risk of all-cause mortality and several cardiovascular complications 6.

Key Findings

• GLP-1 receptor agonists have been shown to reduce the risk of major adverse cardiovascular events (MACE) in patients with type 2 diabetes 3.
• GLP-1 RAs have also been associated with improved renal outcomes, reduced risk of acute kidney injury, and lower risk of allergic reactions 6.
• The effects of GLP-1 RAs on cardiovascular outcomes may be particularly pronounced in certain patient subgroups, such as those with chronic kidney disease or frail patients 2, 3.
• GLP-1 RAs may offer a comprehensive approach to managing obesity and its related comorbidities, potentially improving overall health and survival in this population 6.