October 07, 2024

#320 – AMA 64: New insights on GLP-1 agonists (Ozempic, Wegovy, Mounjaro) - efficacy, benefits, risks, and considerations in the rapidly evolving weight-loss drug landscape

20 minutes

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In this "Ask Me Anything" (AMA) episode, Peter dives back into the increasingly popular topic of GLP-1 agonists, such as Ozempic and Mounjaro, which have garnered widespread attention for their ability to promote weight loss. Peter covers the latest findings in this rapidly evolving landscape, including new insights into their long-term efficacy, side effects, and what happens when the drug is discontinued. Peter also explores their impact on body composition and how resistance training interacts with these treatments. Additionally, he compares different GLP-1 receptor agonists and discusses promising new drugs in the pipeline. Finally, Peter addresses questions about the role of compounding pharmacies in the GLP-1 agonist market, compares oral vs. injectable options, and provides key considerations for anyone deciding whether to use a GLP-1 agonist for weight loss.

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We discuss:

The rapidly evolving landscape of GLP-1 agonists [2:15];
The mechanism of GLP-1 agonists, their origin as diabetes treatments, and how they evolved into weight-loss drugs [6:45];
Overview of new data and open questions related to the benefits and risks of GLP-1 agonists [10:30];
New insights into the long-term safety of GLP-1 agonists, side effects, and more [16:45];
The long-term efficacy of GLP-1 agonists, financial barriers, and more [19:45];
The mechanisms behind GLP-1 agonists' ability to promote weight loss [22:00];
New data on body weight changes after discontinuing the drug [26:00];
Effects of GLP-1 agonists on lean mass and body composition, and the role of protein and resistance training in preserving muscle [31:30];
Semaglutide vs. tirzepatide: comparing benefits and side effects [36:30];
How compounding pharmacies affect availability of GLP-1 drugs and the types of formulations that are available [39:15];
How do oral formulations of GLP-1 drugs compare to injectable formulations? [44:15];
How do sublingual (under tongue) formulations of GLP-1 drugs compare to injectable formulations? [46:15];
Guidance for using compounding pharmacies to purchase GLP-1 agonists [47:15];
Data on retatrutide—a promising new triple receptor agonist in the pipeline [50:15];
Can GLP-1 agonists be beneficial for sleep apnea and immune function? [57:00];
Potential neuroprotective benefits of GLP-1 agonists: impact on dementia risk [1:00:45];
Exploring why GLP-1 agonists may reduce the risk of cancer, kidney disease, and cardiovascular disease [1:04:00];
How GLP-1 agonists might boost fertility in women [1:10:15];
Early indications that GLP-1 agonists may help treat substance abuse disorders [1:12:00];
Potential health risks of GLP-1 agonists: addressing thyroid cancer concerns and the unknowns due to lack of data [1:14:00];
Examining the potential link between GLP-1 agonists and increased depression or suicidal ideation [1:16:00];
Major remaining questions: the effects of cyclic use, rebound appetite, impact on adolescents' development, and more [1:19:30];
Key considerations when deciding whether to use a GLP-1 agonist for weight loss [1:23:45]; and
More.

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By Peter Attia, MD

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