Retatrutide, a new drug that hits three hormone receptors (GLP‑1, GIP, and glucagon), helped people lose a lot of weight in a Phase 2 trial – about 7% at the lowest dose and up to roughly 18% at the highest dose over 24 weeks. The main side effects were typical for this class – nausea, diarrhea and vomiting – and it also raised heart rate by up to 7 beats per minute, which could be a concern. The data look promising for obesity and type‑2 diabetes, but we still need head‑to‑head comparisons with existing drugs like semaglutide or tirzepatide before it can be recommended for self‑experimentation.

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. 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). 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.