The next generation of weight-loss drugs

In this episode of The Lancet Voice, host Callam Davidson and The Lancet's North American Executive Editor, Miriam Sabin, interview Professor Steven Heymsfield about next-generation obesity therapeutics. Professor Heymsfield discusses his early work on cachexia and how it led to his involvement in obesity research, including his experience with the discovery of leptin. The conversation covers currently approved GLP-1 agonists like semaglutide and tirzepatide, their mechanisms of action, and potential long-term adverse effects, drawing parallels with the Fen-Phen example. Professor Heymsfield also discusses the development of bimagromab, which focuses on improving the quality of weight loss by preserving muscle mass. The discussion touches on the potential of oral GLP-1 small molecule inhibitors like orforglipron, global public health implications, equity in access to medications, and the complex interplay between pharmaceutical interventions and public health policies in addressing obesity. The episode concludes with a discussion on the ethical and moral questions surrounding gene therapies and RNA interference approaches to eradicating obesity.