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ABSTRACT
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.
Declaration of interest
The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants, or patents received or pending, or royalties.
Reviewer disclosures
A reviewer on this manuscript has disclosed they are a consultant with Novo Nordisk. A different reviewer has disclosed they appear on Scientific Advisory Boards for Novo Nordisk Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.