GLP-1 Mailbag: Weight Regain, Leptin Resistance, Hypoglycemia & Why Calories Aren’t the Problem

This week on Fat Science, Dr. Emily Cooper, Mark Wright, and Andrea Taylor tackle a wide-ranging mailbag episode with listener questions from the U.S., UK, and Europe. Topics include unexpected weight regain on GLP-1s, post-meal sleepiness and hypoglycemia, metabolic dysfunction despite normal labs, GLP-1 dosing strategies, and why these medications are about metabolism, not appetite suppression.

Key Questions Answered

• Why can weight regain happen on GLP-1s even when habits haven’t changed?
• How do leptin, ghrelin, injury, stress, and under-fueling affect weight regulation?
• What does it mean if you get extremely sleepy after meals—is it hypoglycemia?
• Do GLP-1s increase insulin in a harmful way for non-diabetics?
• Can you have metabolic dysfunction with normal A1C, cholesterol, and blood pressure?
• Do GLP-1 medications “wear off,” and how should dosing be adjusted long term?
• Are GLP-1s just appetite suppressants—or true metabolic treatment?
• Is it possible to undo decades of calorie counting and restriction-based thinking?
• What are the risks of the return to extreme thinness in celebrity culture?

Key Takeaways

• Calories don’t explain metabolism. GLP-1 and GIP work across the brain and body—repairing signaling, not just reducing appetite.
• Leptin matters after dieting. Years of restriction and weight cycling can weaken leptin signaling, making the brain defend weight gain.
• Fueling is foundational. Medication can’t replace adequate food, sleep, and recovery.
• Post-meal fatigue is a clue. Reactive hypoglycemia is common and often misunderstood.
• Lowest effective dose wins. GLP-1 success is about pacing, not racing to the max dose.
• Chasing the “last 10 pounds” can backfire. Cosmetic restriction can create new metabolic problems.

Dr. Cooper’s Actionable Tips

• If weight gain appears after injury or stress, focus first on sleep, regular meals, and full fueling, not restriction.
• Suspected hypoglycemia? Ask about a mixed meal tolerance test to assess glucose and insulin response.
• Stay on the lowest GLP-1 dose that’s working and adjust only when progress truly stalls.
• Push back on “appetite suppressant” language—these meds amplify hormones your body already makes.

Notable Quote

“GLP-1s aren’t about eating less—they’re about strengthening metabolic signaling” — Dr. Emily Cooper

Links & Resources

Podcast Home: Fat Science Podcast Website – https://fatsciencepodcast.com/

Podcast Episode References: https://fatsciencepodcast.com/wp-content/uploads/2025/06/Scientific-References-Fat-Science-Episodes.pdfCooper Center for Metabolism & Fat Science Episodes: https://coopermetabolic.com/podcast/
Resources from Dr. Cooper: https://coopermetabolic.com/resources/
Submit a Show Question: questions@fatsciencepodcast.com
Dr. Cooper direct show email: dr.c@fatsciencepodcast.com

Fat Science breaks diet myths and advances the science of real metabolic health. No diets, no agendas—just science that makes you feel better. This show is informational only and does not constitute medical advice.