Episode 1 - Stop GLP-1s…Then What? | The Truth About Weight Gain.

In Episode 1 of The GLP-1 MasterClass, Dr. Subodh Verma is joined by endocrinologist Dr. Jennifer Green to explore one of the most important and misunderstood questions in obesity and cardiometabolic medicine: what happens after discontinuing GLP-1 therapy?

Together, they discuss:

• why hunger and “food noise” often return after stopping treatment

• how GLP-1 therapies work within the brain and metabolic system • why weight regain is biologically driven, not a failure of willpower

• how cardiovascular and metabolic risk factors may gradually return after discontinuation

• why obesity is increasingly understood as a chronic biologically regulated disease

• why GLP-1 therapies may need to be approached as long-term disease management tools

• the emotional experience many patients feel when weight returns

• how GLP-1 therapies are reshaping cardiovascular prevention medicine

• muscle mass, muscle strength, resistance training, and preserving health during weight loss

• why reducing stigma around obesity remains critically important

This conversation is part of The GLP-1 MasterClass — a 10-part series from The Six Health exploring the future of cardiometabolic medicine, obesity, cardiovascular disease, inflammation, kidney health, and prevention science.

GUEST EXPERT

Jennifer B. Green, MD, Endocrinologist Professor of Medicine Duke University Medical Center, Division of Endocrinology Duke Clinical Research Institute, Durham, North Carolina

References

1. Wilding JPH, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021.

2. Rubino D, et al. Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity: The STEP 4 Randomized Clinical Trial. JAMA. 2021.

3. Wilding JPH, et al. Weight Regain and Cardiometabolic Effects After Withdrawal of Semaglutide: The STEP 1 Trial Extension. Diabetes Obes Metab. 2022.

4. SELECT Trial Investigators. Semaglutide and Cardiovascular Outcomes in Obesity Without Diabetes. N Engl J Med. 2023.

5. WHO Guideline on GLP-1 Therapies for Obesity in Adults. JAMA. 2025.

This content is intended for educational and informational purposes only and should not be considered personal medical advice. Please consult your physician or qualified healthcare provider regarding your individual health needs.

Episode 2 - GLP-1s and Muscle Loss. Fact or Fear?

In Episode 2 of The GLP-1 MasterClass, Dr. Subodh Verma is joined by endocrinologist Dr. Jennifer Green to explore one of the most discussed and misunderstood topics in obesity medicine today: muscle loss during GLP-1 therapy.

Together, they separate fact from fiction and examine what clinical trials actually tell us about lean mass, muscle strength, body composition, and healthy weight loss.

Together, they discuss:

• whether concerns about muscle loss with GLP-1 therapies are justified

• why most weight lost during treatment is fat rather than muscle

• the difference between lean mass, muscle mass, and muscle strength

• what the clinical evidence tells us about body composition changes during weight loss

• practical strategies to preserve muscle strength, including protein intake and resistance training

• why health, strength, and function matter more than the number on the scale

This conversation is part of The GLP-1 MasterClass - a 10-part series from The Six Health exploring the future of cardiometabolic medicine, obesity, cardiovascular disease, inflammation, kidney health, and prevention science.

GUEST EXPERT

Jennifer B. Green, MD, Endocrinologist Professor of Medicine Duke University Medical Center, Division of Endocrinology Duke Clinical Research Institute, Durham, North Carolina

References

1. Wilding JPH, Batterham RL, Calanna S, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021;384(11):989-1002.

2. Rubino D, Abrahamsson N, Davies M, et al. Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity: The STEP 4 Randomized Clinical Trial. JAMA. 2021;325(14):1414-1425.

3. Sattar N, McGuire DK, Pavo I, et al. Tirzepatide and Body Composition in Adults With Overweight or Obesity: A Substudy of the SURMOUNT-1 Trial. Obesity. 2024.

4. Tan S, Gao Y, Wang J, et al. Effects of GLP-1 Receptor Agonists on Body Composition in Adults With Overweight or Obesity: A Systematic Review and Network Meta-analysis. Diabetes Obes Metab. 2024.

5. Cava E, Yeat NC, Mittendorfer B. Preserving Healthy Muscle during Weight Loss. Adv Nutr. 2017;8(3):511-519.

6. Weimann A, Braga M, Carli F, et al. ESPEN Practical Guideline: Clinical Nutrition in Surgery. Clin Nutr. 2021;40(7):4745-4761.

7. Bauer J, Biolo G, Cederholm T, et al. Evidence-Based Recommendations for Optimal Dietary Protein Intake in Older People. J Am Med Dir Assoc. 2013;14(8):542-559.

This content is intended for educational and informational purposes only and should not be considered personal medical advice. Please consult your physician or qualified healthcare provider regarding your individual health needs.

Episode 3 - Pills or Injections? Does It Really Matter?

In Episode 3 of The GLP-1 MasterClass, Dr. Subodh Verma is joined by endocrinologist Dr. Jennifer Green to explore one of the most important developments in obesity and cardiometabolic medicine today: the evolution of oral GLP-1 therapies.

As the use of GLP-1 receptor agonists continues to expand, many patients and clinicians are asking an important question: do oral GLP-1 medications work as well as injectable therapies?

Together, they discuss:

• whether oral GLP-1 medications can be as effective as injectable therapies

• how oral GLP-1 treatments work and why developing them was such a scientific challenge

• what the latest evidence shows about weight loss and cardiovascular benefits with oral semaglutide

• the advantages and limitations of both oral and injectable options

• why finding a treatment that fits a person’s preferences and lifestyle is essential for long-term success

• how new oral therapies may expand access, increase choice, and shape the future of obesity and diabetes care

This conversation is part of The GLP-1 MasterClass - a 10-part series from The Six Health exploring the future of cardiometabolic medicine, obesity, cardiovascular disease, inflammation, kidney health, and prevention science.

GUEST EXPERT

Jennifer B. Green, MD, Endocrinologist Professor of Medicine Duke University Medical Center, Division of Endocrinology Duke Clinical Research Institute, Durham, North Carolina

References

1. Davies M, Pieber TR, Hartoft-Nielsen ML, Hansen OKH, Jabbour S, Rosenstock J. Effect of Oral Semaglutide Compared With Placebo and Subcutaneous Semaglutide on Glycemic Control in Patients With Type 2 Diabetes. JAMA. 2017;318(15):1460-1470.

2. Husain M, Birkenfeld AL, Donsmark M, et al. Oral Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. N Engl J Med. 2019;381(9):841-851.

3. O’Neil PM, Birkenfeld AL, McGowan B, et al. Efficacy and Safety of Oral Semaglutide for Weight Management in Adults With Overweight or Obesity. Lancet. 2023.

4. Aroda VR, Rosenstock J, Terauchi Y, et al. PIONEER Clinical Trial Program: Oral Semaglutide in Type 2 Diabetes. Diabetes Ther. 2020;11:1545-1560.

5. Wharton S, Astrup A, Endahl L, et al. Estimating Treatment Effects of Oral Semaglutide for Obesity Management. Obesity. 2023.

6. Drucker DJ. Advances in Oral Peptide Therapeutics and Incretin Biology. Cell Metabolism. 2024.

7. Green JB, Bethel MA, Armstrong PW, et al. Contemporary Perspectives on GLP-1 Receptor Agonist Therapy and Cardiometabolic Disease Prevention. Circulation. 2024.

This content is intended for educational and informational purposes only and should not be considered personal medical advice. Please consult your physician or qualified healthcare provider regarding your individual health needs.