Why does GLP ‐1 agonist combined with GIP and/or GCG agonist have greater weight loss effect than GLP ‐1 agonist alone in obese adults without type 2 diabetes?

🥉 Top 5% JournalNov 26, 2024Diabetes, obesity & metabolism

Why combining GLP-1 with GIP and/or GCG agonists causes more weight loss than GLP-1 alone in obese adults without diabetes

AI simplified

GLP-1 Therapies on OpenScience ↗PubMed ↗DOI ↗

Abstract

Liraglutide and semaglutide, both approved for long-term weight management, significantly reduce food intake and delay gastric emptying.

Unimolecular polypharmacology represents an advance in obesity treatment by using single molecules to target multiple pathways.
Tirzepatide, a dual agonist, activates both GLP-1 and GIP receptors, showing enhanced weight loss potency compared to traditional GLP-1 mono agonists.
Preliminary data indicate that GLP-1/glucagon dual agonists and GLP-1/GIP/glucagon triple agonists may provide better weight loss results than GLP-1 mono agonists.
Understanding the mechanisms of these unimolecular multitargeting agents could inform future clinical applications and drug development for obesity.

AI simplified

Obesity is a chronic condition demanding effective treatment strategies, among which pharmacotherapy plays a critical role. As glucagon-like peptide-1 (GLP-1) agonist approved by the Food and Drug Administration (FDA) for long-term weight management in adults with obesity, liraglutide and semaglutide have great weight loss effect through reducing food intake and delaying gastric emptying. The emergence of unimolecular polypharmacology, which utilizes single molecules to simultaneously target multiple receptors or pathways, marked a revolutionary improvement in GLP-1-based obesity pharmacotherapy. The dual agonist tirzepatide activates both GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) receptors and has shown enhanced potency for weight loss compared to conventional GLP-1 mono agonist. Furthermore, emerging data suggests that unimolecular GLP-1/glucagon (GCG) dual agonist, as well as GLP-1/GIP/GCG triple agonist, may offer superior weight loss efficacy over GLP-1 agonist. This review summarizes the comprehensive mechanisms underlying the pronounced advantages of GLP-1/GIP dual agonist, GLP-1/GCG dual agonist and GLP-1/GIP/GCG triple agonist over GLP-1 mono agonist in weight reduction in obese adults without type 2 diabetes. A deeper understanding of these unimolecular multitargeting GLP-1-based agonists will provide insights for their clinical application and guide the development of new drugs for obesity treatment.

Full Text

Full text is available at the source.

View full text ↗

Abstract

Full Text

Related papers