Review Explores Impact of GLP-1 Agonists on Type 2 Diabetes and Weight Management

Published in eClinical Medicine, the review reveals that GLP-1RAs are particularly effective in reducing HbA1c levels, facilitating weight loss, and providing cardiovascular protective effects. The authors emphasize that ongoing development and application of GLP-1RAs can significantly enhance treatment outcomes for individuals affected by these conditions.

Obesity and type 2 diabetes mellitus (T2DM) represent major global health challenges, with their prevalence steadily increasing. The authors note that GLP-1RAs have become crucial for managing blood glucose levels, promoting weight loss, preventing cardiovascular diseases, and improving kidney health.

GLP-1, an incretin hormone, plays a vital role in glucose metabolism and appetite regulation, affecting insulin secretion, sensitivity, and gastric emptying. The therapeutic use of GLP-1RAs has evolved, with various formulations offering different efficacy levels, administration routes, and dosing flexibility.

Nasreen Alfaris from the Obesity, Endocrine, and Metabolism Center, King Fahad Medical City, Riyadh, and colleagues investigated the mechanisms of action of GLP-1RAs in treating T2DM and obesity. The review examined GLP-1RAs currently in clinical use and those under investigation, highlighting their clinical benefits, potential side effects, and cost-effectiveness. It also proposed a treatment algorithm for effectively managing obesity and T2DM using these agents.

The research indicates that GLP-1RAs enhance insulin secretion, improve insulin sensitivity, and decrease hepatic glucose production, playing a crucial role in blood glucose regulation. Their effects on appetite suppression and satiety contribute significantly to weight loss.

With a range of GLP-1RAs available—from short-acting to long-acting formulations—clinicians can tailor treatments to individual needs. The emergence of novel agents like tirzepatide and other dual and triple hormonal agonists expands the therapeutic landscape for managing T2DM effectively.

In terms of obesity management, GLP-1RAs have demonstrated significant efficacy in promoting weight loss and improving cardiometabolic parameters. Agents such as liraglutide, semaglutide, tirzepatide, orforglipron, and retatrutide have shown substantial weight reductions, both as monotherapy and in combination with lifestyle interventions.

Dual and triple receptor agonists like tirzepatide and retatrutide offer advantages by targeting multiple pathways involved in energy regulation, resulting in enhanced weight loss and improved metabolic outcomes compared to traditional GLP-1RAs. However, safety profiles, particularly gastrointestinal adverse effects, should be considered.

Concerns regarding potential risks, including pancreatitis, thyroid disorders, and depression associated with GLP-1RAs, necessitate careful monitoring and further investigation. Ongoing research is essential for a deeper understanding of long-term safety and efficacy of these medications across diverse patient populations.

"Overall, GLP-1RAs represent a valuable class of medications with diverse applications in diabetes management, offering hope for improved outcomes and enhanced quality of life for individuals with diabetes and obesity," the researchers concluded.

Reference:

Alfaris, N., Waldrop, S., Johnson, V., Boaventura, B., Kendrick, K., & Stanford, F. C. (2024). GLP-1 single, dual, and triple receptor agonists for treating type 2 diabetes and obesity: A narrative review. EClinicalMedicine, 75, 102782. https://doi.org/10.1016/j.eclinm.2024.102782