Drive with Dr. Peter Attia

Podcast Notes Key Takeaways

• GLP-1 and GIP both started as drugs to control glucose and insulin resistance in people developing or with type 2 diabetes
• Studies showed the added benefit of GLP-1 agonists on weight loss but the mechanism is unclear, though they do reduce appetite in some way

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In this “Ask Me Anything” (AMA) episode, Peter focuses the discussion on two topics getting a lot of attention recently. He first dives deep into GLP-1 agonists, most notably semaglutide and tirzepatide, which originally came to market as diabetes drugs but are now being studied and prescribed for weight loss. He walks through the data and compares the effectiveness of the two drugs, the side effects, and perhaps more importantly, his reservations around wide use of these drugs and who he would consider to be a candidate for them. Next, Peter discusses how metformin, another drug originally brought to market for diabetes management, gained popularity as a potential longevity drug even for non-diabetics. Peter gives his take on this possibility and reviews data from a more recent study investigating the question of whether metformin should be used for general “geroprotection.”

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We discuss:

• The hype around semaglutide, tirzepatide, and other GLP-1 agonists for weight loss [2:30];
• Overview of GLP-1 agonists and why these drugs are getting so much attention [6:15];
• Defining the term “geroprotective” [13:30];
• Semaglutide: background, brand names, indications, and more [15:15];
• Tirzepatide: background, brand names, indications, and more [19:15];
• How semaglutide and tirzepatide compare in their efficacy in terms of weight loss and other metabolic health metrics [23:45];
• Data showing sustained weight loss and improved metabolic metrics with after more than a year of using semaglutide and tirzepatide [29:00];
• What happens to body weight when a patient discontinues the medication? [34:45];
• Noteworthy side effects of GLP-1 agonists and similar classes of drugs [40:45];
• Increased resting heart rate and other concerning trends in patients using GLP-1 agonists [45:15];
• Changes in body composition (body fat and lean muscle) in patients on GLP-1 agonists [50:45];
• Possible reasons for the loss of lean muscle mass and tips for protecting lean mass [59:00];
• GLP-1 agonists and thyroid cancer [1:01:30];
• Who might be a candidate for GLP-1 agonists? [1:03:45];
• The large financial cost of this class of drugs [1:08:30];
• Metformin as a geroprotective drug: origin of the idea that metformin could be a longevity agent even for non-diabetic patients [1:11:30];
• A 2022 study on metformin sheds more light on the question of whether metformin should be used for “geroprotection” in non-diabetics [1:21:00];
• Peter’s current approach with metformin for his patients [1:25:15]; and
• More.

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