Recent advances in peptide-based therapies for obesity and type 2 diabetes.

Abstract

Options for the treatment of type 2 diabetes mellitus (T2DM) and obesity have recently been expanded by the results of several large clinical trials with incretin-based peptide therapies. Most of these studies have been conducted with the glucagon-like peptide-1 (GLP-1) receptor agonist semaglutide, which is available as a once weekly subcutaneous injection and once daily tablet, and the once weekly injected dual agonist tirzepatide, which interacts with receptors for GLP-1 and glucose-dependent insulinotropic polypeptide (GIP). In individuals with T2DM these therapies have achieved reductions of glycated haemoglobin (HbA1c) by > 2% and lowered body weight by > 10%. In some studies, these agents tested in non-diabetic, obese individuals at much higher doses have lowered body weight by > 15%. Emerging evidence suggests these agents can also offer cardio-protective and potentially reno-protective effects. Other incretin-based peptide therapies in early clinical development, notably a triple GLP-1/GIP/glucagon receptor agonist (retatrutide) and a combination of semaglutide with the amylin analogue cagrilintide (CagriSema), have shown strong efficacy. Although incretin therapies can incur adverse gastrointestinal effects these are for most patients mild-to-moderate and transient but result in cessation of treatment in some cases. Thus, the efficacy of new incretin-based peptide therapies is enhancing the opportunity to control body weight and blood glucose and improve the treatment of T2DM and obesity.

• Authors: Clifford J Bailey, Peter R Flatt, J Michael Conlon
• Journal: Peptides (Peptides) Vol. 173 Pg. 171149 (Mar 2024) ISSN: 1873-5169 [Electronic] United States
• PMID: 38184193 (Publication Type: Journal Article)
• Copyright: Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Incretins
• Gastric Inhibitory Polypeptide
• Glucagon-Like Peptide 1
• Glucagon-Like Peptide-1 Receptor
• Hypoglycemic Agents

Topics

• Humans
• Diabetes Mellitus, Type 2 (drug therapy)
• Incretins (therapeutic use)
• Gastric Inhibitory Polypeptide (therapeutic use)
• Obesity
• Glucagon-Like Peptide 1 (therapeutic use)
• Body Weight
• Glucagon-Like Peptide-1 Receptor (agonists)
• Hypoglycemic Agents (therapeutic use)