GLP-1: Potential Applications in Bodybuilding

by Andrew Berry on February 28, 2025

Introduction

Unless you have been living under a rock, you must be seeing a lot of hype about the class of compounds we will refer to GLP-1’s. Now while GLP-1 or Glucagon Like Peptide – 1 is just one of the pathways we will be discussing, I think it’s fair to say that most people know what I’m talking about when I refer to these compounds as GLP-1’s. I’m talking about semaglutide, tirzepatide, and retatrutide. Whether it’s in bodybuilding informational pages, YouTube videos or even mainstream media reports and advertisements, GLP-1’s are here to stay. These drugs are cutting-edge pharmacological agents designed to modulate metabolic pathways primarily for the treatment of type 2 diabetes and obesity. They act on key hormonal systems that regulate glucose metabolism, insulin secretion, appetite suppression, and energy expenditure. Given their substantial effects on body composition, there is emerging interest in their potential applications in bodybuilding and fitness sports, where fat reduction and muscle preservation are highly sought after.

Mechanisms of Action

Each of these drugs targets one or more receptors involved in metabolic regulation:

Glucagon-Like Peptide-1 (GLP-1) Receptor Activation
Glucose-Dependent Insulinotropic Polypeptide (GIP) Receptor Activation
Glucagon Receptor Activation

GLP-1 Receptor Activation

GLP-1 is an incretin (hormones released from the gut into the bloodstream to help regulate blood sugar after eating) hormone secreted by intestinal L-cells in response to food intake. It has several physiological effects, primarily aimed at enhancing glucose homeostasis and promoting satiety. GLP-1 receptor activation leads to:

Increased Insulin Secretion: GLP-1 receptor agonists (GLP-1RAs) stimulate insulin release from pancreatic beta cells in a glucose-dependent manner, which helps maintain stable blood sugar levels.
Reduced Glucagon Secretion: By inhibiting glucagon release from pancreatic alpha cells, GLP-1RAs reduce hepatic glucose production, further improving glycemic control.
Delayed Gastric Emptying: GLP-1 slows gastric emptying, prolonging nutrient absorption and reducing postprandial glucose spikes.
Appetite Suppression: Through central nervous system effects, GLP-1 decreases hunger signals in the hypothalamus, leading to reduced food intake and sustained weight loss.

GIP Receptor Activation

GIP is another incretin hormone secreted by K-cells in the small intestine. Historically considered less significant than GLP-1, recent research indicates that dual activation of GLP-1 and GIP receptors has synergistic benefits:

Enhanced Insulin Secretion: Like GLP-1, GIP also stimulates insulin secretion in response to glucose, aiding in glycemic control.
Improved Beta-Cell Function: GIP helps preserve pancreatic beta-cell mass and function, reducing the risk of insulin resistance over time.
Adipose Tissue Modulation: Unlike GLP-1, GIP has been shown to promote fat storage under certain conditions, but when combined with GLP-1 receptor activation, it enhances lipolysis and metabolic efficiency, leading to superior weight loss effects.

Glucagon Receptor Activation

Glucagon is a hormone primarily involved in increasing blood glucose levels through hepatic glycogenolysis and gluconeogenesis. However, its receptor activation has additional metabolic effects that contribute to weight management:

Increased Energy Expenditure: Glucagon receptor activation boosts energy expenditure by stimulating lipolysis and thermogenesis, promoting fat oxidation.
Reduction in Body Fat Mass: Unlike isolated glucagon secretion, which can increase blood sugar, combined activation with GLP-1 and GIP modulates its effects to drive fat loss without excessive hyperglycemia.

Drug Profiles

Semaglutide
Semaglutide is a GLP-1 receptor agonist initially developed for type 2 diabetes and later approved for weight management. Clinical trials have demonstrated significant weight loss effects in both diabetic and non-diabetic populations. Due to its ability to suppress appetite and promote fat oxidation, semaglutide has attracted attention in bodybuilding for its potential to aid in cutting phases.

Tirzepatide
Tirzepatide is a dual GLP-1 and GIP receptor agonist, offering enhanced metabolic benefits compared to semaglutide. Studies suggest that tirzepatide results in greater weight loss and improved glycemic control. Its ability to modulate fat metabolism and preserve muscle mass makes it a compelling option for bodybuilders looking to achieve a lean physique while maintaining muscle.

Retatrutide
Retatrutide is a triple agonist targeting GLP-1, GIP, and glucagon receptors. By incorporating glucagon receptor activation, retatrutide uniquely increases energy expenditure while still suppressing appetite and improving insulin sensitivity. Preliminary data suggest that retatrutide may achieve even greater fat loss than its predecessors, making it an intriguing candidate for extreme body recomposition strategies.

Potential Benefits for Bodybuilders

Fat Reduction: These medications promote significant weight loss by suppressing appetite, increasing energy expenditure, and enhancing lipolysis.
Muscle Preservation: By improving insulin sensitivity and reducing systemic inflammation, they may help mitigate muscle loss during caloric deficits.
Enhanced Recovery: Improved glucose metabolism ensures stable energy availability, aiding in muscle recovery and performance.
Optimized Body Composition: Through targeted hormonal modulation, these agents provide a pharmacological approach to achieving lower body fat percentages while retaining lean mass.

Risks and Considerations

Gastrointestinal Side Effects: Nausea, vomiting, and diarrhea are common side effects, potentially affecting training performance.
Potential Muscle Loss: While these drugs primarily target fat loss, excessive weight reduction without adequate nutrition and resistance training could lead to muscle degradation.
Off-Label Use Risks: None of these drugs are FDA-approved for bodybuilding purposes, and their long-term effects in non-diabetic, lean individuals remain uncertain.
Regulatory and Ethical Issues: Competitive athletes should be cautious as these medications may be prohibited in professional sports organizations.

My Take

I think these drugs offer some unique pathways to maintain and develop a physique that weren’t previously available to us in the past. I have used several of these compounds with myself and clients with success. I do want to mention that I think starting doses should be much lower than what you find prescribed in a clinical setting. For instance, Tirzepatide has a standard starting dose prescribed at 2.5 mg per week and it increases from there, usually after 4 weeks. I like to start at 1.5 mg per week to avoid the sudden negative digestive side effects like constipation and bloating. I also think you can get a lot out of a smaller dose, and you can always increase it from there if needed. I also like to space injections out over 3 weekly preparations vs. 1 bolus dose per week.

I see plenty of applications for use with clients:

Clients that have a hard time sticking to a diet- while these compounds do lower your appetite, it doesn’t make it impossible to eat meals on time. I like to say that it quiets the background food noise. You can eat when it’s time to eat but you are not thinking about food as much between meals.
Clients that have destroyed insulin sensitivity for some reason or another. Maybe add it in as an aid in a recomp or to the working soccer mom that’s stressed to the max.
Clients that want to maintain a lean physique while pushing food back up, such as after a contest prep.
Clients that want to avoid stimulant compounds for health or other reasons.

Note of caution:

Be sure to add kinetic agents like magnesium citrate in the 300-600 mg per day range and an additional serving of fiber.
Be sure to stay well hydrated. These compounds lower the desire for fluids which can lead to dehydration and more gastric distress.
Semaglutide, tirzepatide, and retatrutide represent a new frontier in metabolic modulation with significant implications for weight management and body composition. While their use in bodybuilding remains experimental, their ability to facilitate fat loss while preserving metabolic health makes them attractive tools for those seeking an optimized physique. However, due diligence, medical supervision, and adherence to ethical guidelines are essential before considering their integration into any fitness regimen.

References

Drucker, D. J. (2021). Mechanisms of action and therapeutic application of glucagon-like peptide-1. Cell Metabolism, 34(2), 188-200. https://doi.org/10.1016/j.cmet.2021.06.020

Kushner, R. F., & Calanna, S. (2020). GLP-1 receptor agonists for obesity: Mechanisms of action and implications for body composition. Diabetes, Obesity and Metabolism, 22(Suppl 1), 5-15. https://doi.org/10.1111/dom.14092

Müller, T. D., Finan, B., Bloom, S. R., D’Alessio, D., Drucker, D. J., Flatt, P. R., … & Tschöp, M. H. (2022). Glucagon-like peptide 1 (GLP-1) and its combination therapies with GIP and glucagon for the treatment of obesity and diabetes. Physiological Reviews, 102(2), 515-532. https://doi.org/10.1152/physrev.00023.2021

Jastreboff, A. M., Kaplan, L. M., Frías, J. P., Wu, Q., Du, Y., Gurbuz, S., & Coskun, T. (2022). Tirzepatide once weekly for the treatment of obesity. New England Journal of Medicine, 387(3), 205-216. https://doi.org/10.1056/NEJMoa2206038

Rubino, D. M., Greenway, F. L., Khalid, U., O’Neil, P. M., Skovgaard, D., Hesse, D., & Rosenstock, J. (2022). Effect of weekly subcutaneous semaglutide on weight loss in adults with overweight or obesity: The STEP 1 trial. JAMA, 325(14), 1403-1413. https://doi.org/10.1001/jama.2021.18318

Andrew is a strength coach and nutritionist in the South Burlington, Vermont area. Andrew has worked with John closely for several years and knows the ins and outs of the Mountain Dog philosophy and is an integral part of the team.