Retatrutide in type 2 diabetes mellitus and obesity: an overview

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly used for T2DM and obesity.

An electronic search was conducted in Scopus, PubMed/MEDLINE, and Google Scholar databases. Retatrutide (LY3437943) is a novel triple agonist targeting glucagon receptor (GCGR), glucose-dependent insulinotropic polypeptide receptor (GIPR), and glucagon-like peptide-1 receptor (GLP-1 R). In subjects with type 2 diabetes mellitus (T2DM), decreased glycated hemoglobin (HbA_1c) by up to 2.16% and decreased fasting glucose by up to 69.1 mg/dL have been seen. Weight loss up to 16.94% was observed in subjects with T2DM. Subjects with overweight or obesity experienced a greater weight loss by up to 26.56% (24.15 kg). Reductions in body-mass index and waist circumference were achieved. In subjects with T2DM and overweight or obesity, decreased systolic blood pressure was found. Finally, relative liver fat count in subjects with metabolic dysfunction-associated steatotic liver disease (MASLD) was reduced by up to 86%. Increased frequency of mild-to-moderate gastrointestinal adverse events (mainly nausea, vomiting, constipation, and diarrhea) was reported in participants on the highest retatrutide doses, likely due to rapid dose escalation and higher starting dose.

These promising effects on glycemic control, weight loss, and emerging pleiotropic actions merit further investigation.