Multifunctional incretin peptides in therapies for type 2 diabetes, obesity and associated co-morbidities.
Bailey. Clifford J CJ; Flatt. Peter R PR; Conlon. J Michael JM
Key Findings
- Cagrilintide is being tested together with semaglutide (CagriSema) to give stronger weight‑loss and glucose‑control than GLP‑1 alone.
- Multi‑agonist peptides (GLP‑1/GIP/glucagon or GLP‑1/amylin) are showing added benefits for cardiovascular, renal, liver, and possibly cognitive health.
- These next‑generation peptides are still in development (2023‑2025) and not yet widely available, but early trials suggest they could outperform current single‑target drugs.
Practical Outcomes
- For biohackers, the takeaway is to watch for CagriSema and similar multi‑agonist peptides as they may become the next big tool for weight loss and metabolic health. Right now they’re experimental, so any use should be limited to clinical trials or under medical supervision. Keep an eye on emerging safety and dosage data as they become available.
Summary
The review talks about the newest wave of peptide drugs that hit several hormone receptors at once. One of the most interesting combos is semaglutide (a GLP‑1 drug) paired with cagrilintide, an amylin‑like peptide, called CagriSema. These multi‑target peptides are shown to lower blood sugar, cut weight, and may also help heart, kidney, liver, and even brain health, but most of the data are still from early trials.
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).
Study Information
pubmed
2025
2025-03-11T00:00:00.000Z
10.1016/j.peptides.2025.171380
10
150