What do meta-analyses say about Glucagon-like peptide-1 (GLP-1)?

From the Guidelines

GLP-1 agonists are recommended as a first-line treatment for type 2 diabetes management due to their ability to reduce all-cause mortality, major adverse cardiovascular events, and severe hypoglycemia, as demonstrated in a recent systematic review and network meta-analysis 1.

Key Findings

• GLP-1 agonists have been shown to reduce severe hypoglycemia and major adverse cardiovascular events compared to sulfonylureas and insulin 1.
• A network meta-analysis found that GLP-1 agonists, along with SGLT2 inhibitors, reduce all-cause mortality and major adverse cardiovascular events compared to usual care 1.
• The medications work by mimicking the incretin hormone GLP-1, stimulating insulin secretion, suppressing glucagon, delaying gastric emptying, and increasing satiety through central nervous system effects.

Clinical Implications

• Treatment with GLP-1 agonists typically begins with weekly injections at a low dose, gradually increasing over several weeks to minimize gastrointestinal side effects like nausea, vomiting, and diarrhea.
• Patients should be monitored for potential side effects, including pancreatitis and thyroid C-cell tumors, although these are rare but serious concerns.
• Meta-analyses demonstrate that GLP-1 agonists provide cardiovascular benefits, reducing major adverse cardiovascular events by 12-15% in high-risk patients, as reported in a study on cardiovascular disease and risk management 1.

Medication Options

• Semaglutide (Ozempic, Wegovy), liraglutide (Victoza, Saxenda), dulaglutide (Trulicity), and tirzepatide (Mounjaro) are examples of GLP-1 agonists that have shown impressive results in terms of A1C reductions and weight loss.
• These medications are generally well-tolerated long-term, making them a viable option for patients with type 2 diabetes.

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Meta-Studies on GLP-1

• Meta-studies have shown that GLP-1 receptor agonists (GLP-1 RAs) are effective in reducing the incidence of major adverse cardiovascular events (MACE) in type 2 diabetes (T2D) 2, 3, 4.
• GLP-1 RAs have been found to reduce the risk of hospitalization for heart failure (HHF) and kidney events, as well as all-cause mortality 3, 5, 4.
• The benefits of GLP-1 RAs extend to both subcutaneous and oral formulations, with no significant heterogeneity by administration route 4.
• GLP-1 RAs have been found to have a low risk of hypoglycemia and do not increase the risk of severe hypoglycemia, retinopathy, or pancreatic events 6, 4.

Cardiovascular and Kidney Outcomes

• Long-acting GLP-1 RAs have been found to reduce the incidence of MACE by 14% and HHF by 14% 4.
• GLP-1 RAs have also been found to reduce the composite kidney outcome by 17% and all-cause mortality by 12% 4.
• The benefits of GLP-1 RAs on cardiovascular and kidney outcomes are consistent across different patient populations, including those with established cardiovascular disease or chronic kidney disease 2, 3, 5.

Clinical Practice Guidelines

• Clinical practice guidelines recommend the use of GLP-1 RAs as a first-line treatment for T2D, particularly in patients with established cardiovascular disease or chronic kidney disease 3, 5.
• The guidelines also recommend the use of GLP-1 RAs in patients with multiple cardiovascular risk factors, even if they do not have established cardiovascular disease 5.
• The choice of GLP-1 RA should be individualized based on patient characteristics, such as the presence of cardiovascular disease or chronic kidney disease, and the patient's values and preferences 5.