According to Gram Research analysis, GLP-1 medications produce weight loss of 15 to 22 percent, but some of this loss is muscle rather than fat. Researchers propose that men with obesity and low testosterone might benefit from combining testosterone therapy with these medications to preserve muscle and prevent fat regain after stopping treatment. However, this idea remains theoretical and requires clinical trials before doctors can recommend it.
A new research paper explores why men regain weight after stopping GLP-1 medications like Ozempic and Wegovy, which help people lose 15 to 22 percent of their body weight. The researchers noticed that some of this weight loss comes from muscle, not just fat. They propose that men with low testosterone might benefit from combining testosterone therapy with these weight-loss drugs to preserve muscle and prevent regaining fat. However, this is still just a theory that needs testing in actual clinical trials before doctors can recommend it.
Key Statistics
A review published in Diabetes, Obesity and Metabolism in 2026 found that GLP-1 receptor agonist medications achieve placebo-subtracted weight loss of 15 to 22 percent, though the composition of this weight loss includes both fat and lean tissue.
Research shows that men with obesity commonly have low or low-normal testosterone levels, which is associated with reduced muscle mass, increased belly fat, and impaired insulin sensitivity.
According to the 2026 hypothesis paper, no lifestyle measure reliably prevents the fat-predominant weight regain that follows when people discontinue weight-loss diets, despite high adherence to exercise and diet during active weight loss.
The Quick Take
- What they studied: Why men regain weight after stopping GLP-1 medications (like Ozempic) and whether adding testosterone therapy could help prevent that regain
- Who participated: This was a theoretical review paper, not a study with participants. The authors analyzed existing research and proposed a new idea for future testing
- Key finding: GLP-1 medications cause weight loss of 15 to 22 percent, but some of that loss is muscle mass rather than fat. Men with low testosterone may lose even more muscle, which could lead to more fat regain when they stop the medication
- What it means for you: If you are a man taking GLP-1 medications and have low testosterone, this research suggests combining testosterone therapy might help you keep the weight off longer. However, this is not yet proven and requires clinical trials before doctors can recommend it
The Research Details
This paper is a review and hypothesis paper, not a traditional research study. The authors examined what we know about GLP-1 medications (drugs like Ozempic and Wegovy that help with weight loss) and noticed a potential problem: when people lose weight on these drugs, they lose both fat and muscle. The authors then looked at what happens to men with obesity who also have low testosterone levels. They found that low testosterone is linked to losing muscle mass, gaining belly fat, and having worse heart health. Based on this information, the authors proposed a new idea: what if doctors gave men with obesity and low testosterone both GLP-1 medications and testosterone therapy together? They think this combination might help preserve muscle while losing fat, and prevent the weight regain that often happens when people stop taking the medications.
Understanding what type of weight people lose matters because losing muscle is worse than losing fat. Muscle helps your body burn calories and keeps you strong. If GLP-1 medications cause significant muscle loss, especially in men with low testosterone, this could cause health problems even if the scale shows weight loss. This research approach is important because it identifies a potential problem and suggests a solution before widespread use causes harm
This is a hypothesis paper, not a completed study, so it presents ideas that need testing rather than proven facts. The authors clearly state their idea is exploratory and based on limited human data from one small pilot study. They acknowledge that testosterone therapy as a weight-loss aid has not been properly tested in clinical trials. The strength of this paper is that it identifies an important gap in our knowledge and proposes a testable solution. The limitation is that it is entirely theoretical and requires clinical trials before any recommendations can be made
What the Results Show
The authors identified that GLP-1 receptor agonist medications (including newer versions that work on multiple hormone systems) produce weight loss of 15 to 22 percent compared to placebo. However, this weight loss includes both fat and lean tissue, including muscle. The proportion of muscle loss compared to fat loss with these medications is unknown. Men with obesity commonly have low or low-normal testosterone levels, which is associated with reduced muscle mass, increased belly fat, poor blood sugar control, and higher heart disease risk. The authors propose that combining testosterone therapy with GLP-1 medications could preserve muscle mass during weight loss and reduce the fat-predominant weight regain that occurs after stopping the medications.
The paper emphasizes that resistance exercise and adequate protein intake are the first-line approaches for preserving muscle during weight loss. However, no lifestyle measure reliably prevents the fat-predominant weight regain that follows when people stop dieting, and long-term adherence to lifestyle interventions is poor. The authors position testosterone therapy as a potential pharmacological addition to weight-loss treatment in men with obesity and low testosterone, but only after proper clinical trials evaluate its safety and effectiveness
This paper builds on existing knowledge that GLP-1 medications are highly effective for weight loss, achieving results superior to older weight-loss drugs. It adds to growing awareness that the composition of weight loss matters, not just the total amount. The proposal to combine testosterone therapy is novel and represents an evolution in thinking about how to optimize weight loss in men with low testosterone. However, the idea remains untested in rigorous clinical trials
This is a hypothesis paper based on theoretical reasoning and one small, non-randomized pilot study, not a completed clinical trial. The authors have no direct human data showing that testosterone therapy combined with GLP-1 medications actually works. The clinical consequences of muscle loss during GLP-1 treatment are not yet fully understood. The paper does not address potential side effects of testosterone therapy or which men would be appropriate candidates. The idea requires evaluation in randomized controlled trials with proper measurement of muscle mass and safety monitoring before it can guide clinical practice
The Bottom Line
Current evidence supports using GLP-1 medications for weight loss in people with obesity or type 2 diabetes (high confidence). Resistance exercise and adequate protein intake should be used to preserve muscle during weight loss (high confidence). Combining testosterone therapy with GLP-1 medications is a promising idea that requires clinical trials before it can be recommended (low confidence, exploratory stage only). Men with low testosterone considering this approach should discuss it with their doctor and participate in clinical trials if available
Men with obesity who have low or low-normal testosterone levels should be aware of this emerging research. Men currently taking GLP-1 medications who experience significant weight regain after stopping should discuss this with their doctor. Researchers and clinicians studying weight loss and testosterone should follow this hypothesis as it develops. Women and men with normal testosterone levels should not assume this applies to them without further research
This research is in the hypothesis stage. Clinical trials would likely take 1 to 3 years to complete. If trials show promise, it may take another 2 to 5 years before testosterone combination therapy could become a standard recommendation. Do not expect changes in clinical practice for at least 3 to 5 years
Frequently Asked Questions
Do GLP-1 medications like Ozempic cause muscle loss?
GLP-1 medications produce significant weight loss of 15 to 22 percent, but research shows some of this loss includes lean tissue and muscle, not just fat. The exact proportion of muscle loss compared to other weight-loss methods is unknown and needs further study.
Can testosterone therapy help prevent weight regain after stopping GLP-1 drugs?
This is a promising hypothesis proposed in 2026 research, but it has not been tested in clinical trials yet. The idea is that testosterone might preserve muscle mass in men with low testosterone, potentially preventing fat regain, but this requires proper testing before doctors can recommend it.
What should men do to keep muscle while taking weight-loss medications?
Resistance exercise 2 to 3 times per week and adequate protein intake are the first-line approaches for preserving muscle during weight loss. Discuss testosterone testing with your doctor if you have symptoms of low testosterone, as this may affect your results.
Why do people regain weight after stopping GLP-1 medications?
Research shows that weight regain after stopping weight-loss diets is primarily fat rather than muscle, and no lifestyle measure reliably prevents this regain. The mechanisms behind this regain are not fully understood, which is why researchers are exploring combination therapies.
Is it safe to combine testosterone therapy with GLP-1 medications?
The safety of combining these treatments has not been studied in clinical trials. Before considering this combination, men should discuss testosterone testing and potential risks with their doctor. Any new treatment combination requires medical supervision and proper monitoring.
Want to Apply This Research?
- Track weekly weight, waist circumference, and muscle mass (via bioelectrical impedance or DEXA scan if available). Monitor energy levels and strength during resistance exercise to detect muscle loss early
- If taking GLP-1 medications, perform resistance exercise 2 to 3 times per week and consume adequate protein (0.7 to 1 gram per pound of body weight daily). Discuss testosterone testing with your doctor if you have symptoms of low testosterone
- Monthly check-ins on weight composition, quarterly testosterone level testing if applicable, and ongoing tracking of exercise performance and muscle strength to detect changes early
This article discusses a hypothesis paper proposing testosterone therapy as a potential adjunct to GLP-1 medications. This is not yet proven and should not be considered medical advice. The combination of testosterone therapy with GLP-1 medications has not been tested in clinical trials and is not currently recommended by medical organizations. Men considering any weight-loss treatment, especially those with low testosterone or other health conditions, should consult with their healthcare provider before starting new medications. Testosterone therapy carries potential risks and side effects that must be discussed with a doctor. This research is in the exploratory stage and requires clinical trials before it can inform clinical practice.
This research translation is published by Gram Research, the science division of Gram, an AI-powered nutrition tracking app.