New Amylin-Based Agonists for the Treatment of Obesity and Type 2 Diabetes Mellitus
- 1Second Department of Internal Medicine, Diabetes Centre, Democritus University of Thrace, Alexandroupolis, Greece
- 2Clinic for Endocrinology, Diabetes and Metabolic Disorders, Clinical Centre of Vojvodina, Novi Sad, Serbia
- 3Medical Faculty, University of Novi Sad, Novi Sad, Serbia
Abstract
Introduction: Type 2 diabetes mellitus (T2DM) and obesity represent two major global health challenges. Amylin-based agonists offer a promising perspective. Three frontrunner agents of this class are increasingly being investigated: zenagamtide, eloralintide and cagrilintide–semaglutide (CagriSema).
Methods: A search in PubMed/MEDLINE, Scopus and Google Scholar was conducted with the use of appropriate keywords until June 2026 for this narrative review.
Results: Zenagamtide (formerly known as amycretin), a unimolecular long-lasting amylin and glucagon-like peptide-1 receptor (GLP-1R) co-agonist, achieved weight loss up to 13.1% (phase 1 study, 85 days) in obesity trials as an oral formulation and up to 24.3% (phase 1b/2a study, 36 weeks) as a subcutaneous formulation. Moreover, eloralintide, a long-acting mostly amylin type 1 receptor (AMY1R) agonist, achieved weight loss up to 20.1% (phase 2 study, 48 weeks), and CagriSema resulted in weight loss up to 22.7% (phase 3a study, 68 weeks). All these agents reduced body mass index (BMI) and waist circumference (WC). In T2DM, CagriSema reduced glycated haemoglobin (HbA1c) by up to 2.0% (trial product estimand, phase 3a study, 68 weeks) and is currently the most well-studied agent in T2DM. In treatment-naïve people with T2DM, this agent has been successfully used, leading even to T2DM remission in approximately one out of two CagriSema users (phase 3a, 40 weeks). In individuals with T2DM receiving basal insulin, it reduced insulin dose by 20 units compared with the control arm (phase 3a, 40 weeks). The safety profile of amycretin and CagriSema is overall consistent with that of glucagon-like peptide 1 receptor agonists (GLP-1RAs). Preliminary evidence suggests that eloralintide, as an AMY1R monoagonist, was associated with a distinct adverse events profile, including fatigue, headache and appetite loss.
Conclusions: These agents hold therapeutic potential in the management of both T2DM and obesity, as shown by preliminary clinical trial outcomes. Further trials are now needed to validate them in clinical practice.
Related
- Glucagon-like Peptide-1 Receptor Agonists in Treating Diabetes Mellitus and Weight Loss with Potential Application to Rare Obesity-related Genetic Disorders: A Commentary
- Neuropsychiatric Safety of GLP-1 Receptor Agonists and Tirzepatide in Adults with Type 2 Diabetes Mellitus or Obesity.
- Janus Polymeric Nanorods Inhibit human Amylin Oligomerization and Fibrillation for Potential Type 2 Diabetes Treatment
- GLP-1 Receptor Agonists and Obesity-Related Cancer by Diabetes Severity
- Modern Obesity Treatment: Efficacy, Safety, and Future Directions of GLP-1 (Glucagon-Like Peptide-1) and GIP (Glucose-Dependent Insulinotropic Polypeptide) Receptor Agonists
BibTeX
@article{panou2026amylinbased,
title = {{New Amylin-Based Agonists for the Treatment of Obesity and Type 2 Diabetes Mellitus}},
author = {Theodoros Panou and Evanthia Gouveri and Djordje S. Popovic and Nikolaos Papanas},
journal = {Diabetes Therapy},
year = {2026},
month = sep,
doi = {10.1007/s13300-026-01921-0},
url = {https://doi.org/10.1007/s13300-026-01921-0},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - New Amylin-Based Agonists for the Treatment of Obesity and Type 2 Diabetes Mellitus
AU - Theodoros Panou
AU - Evanthia Gouveri
AU - Djordje S. Popovic
AU - Nikolaos Papanas
PY - 2026
DA - 2026/09/28
JO - Diabetes Therapy
DO - 10.1007/s13300-026-01921-0
UR - https://doi.org/10.1007/s13300-026-01921-0
AB - Introduction: Type 2 diabetes mellitus (T2DM) and obesity represent two major global health challenges. Amylin-based agonists offer a promising perspective. Three frontrunner agents of this class are increasingly being investigated: zenagamtide, eloralintide and cagrilintide–semaglutide (CagriSema). Methods: A search in PubMed/MEDLINE, Scopus and Google Scholar was conducted with the use of appropriate keywords until June 2026 for this narrative review. Results: Zenagamtide (formerly known as amycretin), a unimolecular long-lasting amylin and glucagon-like peptide-1 receptor (GLP-1R) co-agonist, achieved weight loss up to 13.1% (phase 1 study, 85 days) in obesity trials as an oral formulation and up to 24.3% (phase 1b/2a study, 36 weeks) as a subcutaneous formulation. Moreover, eloralintide, a long-acting mostly amylin type 1 receptor (AMY1R) agonist, achieved weight loss up to 20.1% (phase 2 study, 48 weeks), and CagriSema resulted in weight loss up to 22.7% (phase 3a study, 68 weeks). All these agents reduced body mass index (BMI) and waist circumference (WC). In T2DM, CagriSema reduced glycated haemoglobin (HbA1c) by up to 2.0% (trial product estimand, phase 3a study, 68 weeks) and is currently the most well-studied agent in T2DM. In treatment-naïve people with T2DM, this agent has been successfully used, leading even to T2DM remission in approximately one out of two CagriSema users (phase 3a, 40 weeks). In individuals with T2DM receiving basal insulin, it reduced insulin dose by 20 units compared with the control arm (phase 3a, 40 weeks). The safety profile of amycretin and CagriSema is overall consistent with that of glucagon-like peptide 1 receptor agonists (GLP-1RAs). Preliminary evidence suggests that eloralintide, as an AMY1R monoagonist, was associated with a distinct adverse events profile, including fatigue, headache and appetite loss. Conclusions: These agents hold therapeutic potential in the management of both T2DM and obesity, as shown by preliminary clinical trial outcomes. Further trials are now needed to validate them in clinical practice.
SN - 1869-6953
SN - 1869-6961
ER -