Stephan Guyenet, PhD: GLP-1, Semaglutide, and the Big Future of Weight Loss Therapies

The External Medicine Podcast

In this interview, Mitch Belkin and Daniel Belkin speak with Stephan Guyenet, PhD, about Glucagon-like peptide-1 (GLP-1) and Semaglutide. They discuss GLP-1’s mechanisms of action, Anthony Sclafoni’s experiments on food reinforcement and nutrient receptors in the small intestines. Finally, they touch on some exciting new weight loss drugs that may replace semaglutide and potentially even bariatric surgery.
Who is Stephan Guyenet?

Dr. Stephan Guyenet received his PhD in Neurobiology and Behavior from the University of Washington. Afterward, he completed a postdoctoral fellowship in the neuroscience of obesity. He is the author of the book The Hungry Brain. Dr. Guyenet is the founder & director of Red Pen Reviews, which publishes expert reviews of popular nutrition books with structured semi-quantitative evaluations. In addition, he is a senior researcher at GiveWell where he conducts cost effectiveness analyses on water quality interventions and malnutrition treatments in low income countries.

What is GLP-1 ?

Glucagon-like peptide-1 is a hormone produced by the intestines. It is an incretin, meaning it signals the pancreas to increase insulin secretion in a glucose-dependent manner. Initially, GLP-1 agonists were developed for the treatment of diabetes. In both animal and human models, it was discovered that GLP-1 agonists suppress food intake, which led to weight loss. This discovery spurred its use in obesity trials, including STEP 1.

Citations for Stephan Guyenet:

• @WHsource
• The Promise and Impact of the Next Generation of Weight Loss Drugs
• NEJM - Once-Weekly Semaglutide in Adults with Overweight or Obesity
• Safety, tolerability, pharmacokinetics, and pharmacodynamics of concomitant administration of multiple doses of cagrilintide with semaglutide 2·4 mg for weight management: a randomised, controlled, phase 1b trial
• Danuglipron (PF-06882961) in type 2 diabetes: a randomized, placebo-controlled, multiple ascending-dose phase 1 trial
• Diabetes Prevention Program - 58% reduction in progression from pre-diabetes to diabetes.
• Stephanguyenet.com
• March 2021 article in Works in Progress

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