Ep. 262, Chapter 2: Foundational Obesity Research Enables Therapeutic Breakthroughs With Roger Cone, Ph.D.

11:56 – 18:39

Progress in obesity research was powered by fundamental research that uncovered the mechanisms regulating hunger and satiety, including gut peptides like GLP-1 and the central melanocortin system. This foundational research led to two distinct, highly effective therapeutic approaches. One approach, exemplified by setmelanotide (Imcivree), is a melanocortin-4 (MC4) receptor agonist used for rare syndromic forms of obesity. This drug effectively normalizes body weight in patients with defects in their primary melanocortin system.

The second approach, built on an understanding of GLP-1 biology, led to the development of drugs like Wegovy and Mounjaro. Native GLP-1 is a gut peptide with a very short half-life, limiting its effect on hunger. By tweaking the molecule to be more stable and long-acting, pharmaceutical companies have created GLP-1 analogs that produce significant and safe weight loss, ranging from 5% to over 15% in some cases.