Study summary · research use only
Multifunctional incretin peptides in therapies for type 2 diabetes, obesity and associated co-morbidities
Plain-language summary
Paraphrased from the published abstract below — not a verdict on whether anything works.
This review discusses peptide-based incretin therapies for type 2 diabetes, obesity, and related comorbidities in humans, focusing on the GLP-1 receptor agonist semaglutide and the dual GLP-1/GIP agonist tirzepatide. The abstract reports glucose-lowering and weight-lowering effects across diverse populations, including different ethnic groups and ages, and protection against cardiovascular and renal disease progression, with emerging evidence for benefit in fatty liver disease, chronic inflammation, sleep apnea, and possibly bone disorders and cognitive decline. New incretin-based peptides in development described include a long-acting glucagon receptor agonist (LY3324954), dual GLP-1/glucagon agonists (survodutide, pemvidutide, mazdutide, G49), triple GLP-1/GIP/glucagon agonists (retatrutide, efocipegtrutide), semaglutide plus cagrilintide (CagriSema), a GLP-1/amylin dual agonist (amycretin), and a GIP receptor antibody with GLP-1 agonism (MariTide). The review covers developments from 2023 through February 2025.
Abstract
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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