Multifunctional incretin peptides in therapies for type 2 diabetes, obesity and associated co-morbidities

Mar 13, 2025Peptides

Incretin peptides with multiple roles in treatments for type 2 diabetes, obesity, and related health problems

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Abstract

Randomised clinical trials have confirmed the marked glucose-lowering and weight-lowering efficacy of peptide-based therapies for diverse populations.

Incretin therapies have shown effectiveness across various ethnic groups and age ranges, including individuals with and without diabetes.
These therapies are associated with additional protections against cardiovascular and renal disease progression.
Emerging evidence suggests potential benefits for conditions such as fatty liver disease, chronic inflammation, and sleep apnea.
New incretin-based therapies under development include various receptor agonists and combinations aimed at improving management of type 2 diabetes and obesity.

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Recent studies with peptide-based incretin therapies have focussed mainly on the glucagon-like peptide-1 (GLP-1) receptor agonist semaglutide and the dual agonist tirzepatide that engages receptors for GLP-1 and glucose-dependent insulinotropic polypeptide (GIP). Randomised clinical trials and 'real-world' studies have confirmed the marked glucose-lowering and weight-lowering efficacy of these agents across diverse populations. These include different ethnic groups, young and elderly individuals with and without diabetes and/or overweight or obesity. Recent studies have also confirmed protections against the development and progression of cardiovascular and renal diseases that are additive to the benefits conferred by improved control of blood glucose and body weight. Emerging evidence suggests that incretin therapies could additionally ameliorate fatty liver disease, chronic inflammation, sleep apnea and possibly degenerative bone disorders and cognitive decline. New incretin-based peptide therapies in development include a long-acting glucagon receptor agonist (LY3324954), dual GLP-1/glucagon receptor agonists (survodutide, pemvidutide, mazdutide, G49), triple GLP-1/GIP/glucagon receptor agonists (retatrutide, efocipegtrutide), a combination of semaglutide with the amylin analogue cagrilintide (CagriSema), a unimolecular GLP-1/amylin receptor dual agonist (amycretin), and a GIP receptor antibody with GLP-1 receptor agonism (MariTide). The creation of multi-targeting incretin-based synthetic peptides provides opportunities for improved management of type 2 diabetes and obesity as well as new therapeutic approaches to an expanding list of associated co-morbidities. The aim of the review is to acquaint the reader with developments in the field from 2023 to the present (February 2025).

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Multifunctional incretin peptides in therapies for type 2 diabetes, obesity and associated co-morbidities

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