Retatrutide showing promise in obesity (and type 2 diabetes).

INTRODUCTION: Obesity is a major risk factor for cardiovascular disease, diabetes, osteoarthritis, and some cancers. Retatrutide stimulates Glucagon-like peptide 1 (GLP-1), Glucose-dependent insulinotropic polypeptide (GIP) receptors, and glucagon receptors, and is being developed for the treatment of obesity and type 2 diabetes.

AREAS COVERED: A phase 2 clinical trial of retatrutide (LY3437943) in the treatment of obesity. The primary end point was percentage change in weight from baseline to 24 weeks, which ranged from -7.2% to -~18% as the dose of retatrutide increased from 1 mg to 12 mg. The most frequent adverse events were gastrointestinal (nausea, diarrhea, vomiting).

EXPERT OPINION: The results for retatrutide in phase 2 for obesity (and diabetes) are mostly encouraging. Consistent with being a GLP-1 receptor agonist, heart rate was increased by up to 6.7 beats/min by retatrutide, which may be detrimental and offset some of the benefits of weight loss. Presumably, retatrutide is being developed as a challenger to the recently developed weight loss medicines; semaglutide and/or tirzepatide. Thus, comparator studies are needed between retatrutide and these drugs, but none are ongoing and, in my opinion, this lack is a major omission in the development of retatrutide.