By Julie Stewart
Medically Reviewed by Alexander Watson, M.D.If you’re a man with low testosterone, losing weight can feel like an uphill battle. Your energy is low, your metabolism has slowed, and hitting the gym doesn’t deliver the results it used to. That’s where testosterone replacement therapy (TRT) comes in: Restoring testosterone levels helps build muscle, burn fat, and improve motivation.
Then there’s semaglutide, the GLP-1 drug behind Ozempic and Wegovy, which works in an entirely different way to support weight loss: it dials down appetite, stabilizes blood sugar, and shifts the body into fat-burning mode.
Together, testosterone and semaglutide tackle weight loss from both sides for the right candidates. The key? Understanding how they interact, when combining them makes sense, and when it doesn’t. Here’s what experts say about using semaglutide and TRT together for fat loss, muscle growth, and metabolic health.
About the Experts:
Lester Lee, M.D., is a regenerative medicine physician specializing in hormone replacement therapy.
Taylor Kohn, M.D., is a fellow in male reproductive medicine and surgery at Baylor College of Medicine
James Staheli, D.O., is the medical director for Broad Health and a family medicine doctor specializing in hormone treatment for men.
Can You Combine Semaglutide and Testosterone Replacement Therapy?
You can take Semaglutide and testosterone replacement therapy (TRT) together if you have low testosterone and obesity or diabetes, and your doctor clears you for both. In fact, some experts believe pairing semaglutide with testosterone could lead to more weight loss than either drug alone.
“[Using TRT and semaglutide together] seems to be a nice combination for the person who has low testosterone and is trying to lose weight, but just doesn’t necessarily have the energy to be able to go and do workouts,” says Taylor Kohn, M.D., a fellow in male reproductive medicine and surgery at Baylor College of Medicine.
That said, this drug combination isn’t recommended for men with normal testosterone levels. And if you have a condition that makes taking either TRT or semaglutide dangerous—a history of pancreatitis, medullary thyroid cancer, a family history of thyroid cancer, or a heart attack or stroke within the last six months—your doctor will likely advise against it.
While doctors frequently prescribe semaglutide and TRT together, controlled studies on their long-term combined effects are still lacking. That’s why some physicians start patients on one before adding the second.
“When a man has both low testosterone and weight concerns, the initial treatment often targets the most pressing issue,” says James Staheli, D.O., a family medicine doctor who specializes in hormone health. “Severe low testosterone symptoms may necessitate starting with TRT, while significant weight loss goals might prioritize a GLP-1 like semaglutide.”
One of the biggest concerns when starting two medications at the same time is that if a side effect occurs, it can be difficult to know which one caused it, says Staheli.
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Let’s Get StartedWhat to Know About TRT and Ozempic
Although they work in different ways, TRT and semaglutide both help change your body shape.
What is Semaglutide and How Does it Help with Weight Loss?
Semaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist, a class of drugs that regulate appetite, slow digestion, and help control blood sugar.
GLP-1 is a hormone produced naturally in your gut, brain, and pancreas. By activating GLP-1 receptors, semaglutide prompts the pancreas to release more insulin and less glucagon, lowering blood sugar. 1
It also slows gastric emptying, so food stays in your stomach longer, reducing hunger and calorie intake. As a result, semaglutide users lose around 14-17 percent of their body weight on average within four years. 2
Does ozempic affect testosterone?
Ozempic’s effects on testosterone haven’t been extensively researched, and early studies show mixed results about whether it lowers or raises testosterone levels.
One clinical trial found that men with low testosterone and type 2 diabetes who took semaglutide increased their total testosterone by an average of 1.6 nanomoles per liter (nmol/L). The study authors suspect weight loss drives this effect, though GLP-1 agonists may also influence testosterone through their impact on inflammation and hormone signaling in the brain. 3
However, a separate medical records analysis suggested that non-diabetic men using semaglutide were slightly more likely to develop low testosterone than those who weren’t. The risk, though, was small–less than 1.5 percent. 4 Kohn, an author of this study, says men who take semaglutide are likely to see testosterone rise in the long run as they shed fat and produce less estrogen in their fat cells.
Interestingly, while total testosterone may increase with semaglutide use, free testosterone—the form readily available for the body to use—can sometimes decline. This is because hemoglobin A1C (a measure of blood sugar control) and sex hormone-binding globulin (SHBG) are inversely correlated: as A1C improves with weight loss, SHBG levels may rise, which can bind more testosterone and reduce the amount that circulates freely in the bloodstream. 5
What is TRT and How Does it Help with Weight Loss?
Testosterone replacement therapy (TRT) is a prescription form of testosterone that helps restore low blood levels of testosterone to relieve symptoms of low T. It comes in injections, topicals (like testosterone creams), nasal gels, pellets, and lozenge-like troches.
TRT has direct metabolic effects, including:
- Muscle growth: Testosterone directly stimulates muscle protein synthesis, growth, and repair, especially of the fast-twitch muscle fibers that power strength and hypertrophy, says Lee.
- Fat loss: The effects compound since muscle burns more energy than fat. Higher T levels increase basal metabolic rate, meaning you burn more calories at rest.
- Insulin sensitivity: Losing fat and building muscle both improve insulin sensitivity, making it easier to regulate blood sugar, says Lee. The TRAVERSE trial—a large, well-regarded study on TRT—didn’t find a significant benefit in preventing worsening insulin resistance in men with prediabetes. However, a key criticism of the study is that the testosterone doses used were lower than what many clinicians consider therapeutically effective. Mechanistically, testosterone still has a clear role in improving insulin sensitivity indirectly by promoting fat loss and muscle growth, both of which enhance the body’s ability to regulate blood sugar, says Lee. 6
- Energy and motivation: TRT stimulates neurotransmitters—like dopamine, epinephrine, and norepinephrine—in the brain, which improves mood, focus, and motivation, says Lee.
In one study, men with low testosterone who used TRT lost about 11 pounds of fat and gained about nine pounds of lean mass over 18 months. 7
The Benefits of Combining Semaglutide and TRT
Pairing semaglutide with testosterone replacement therapy may help men with low testosterone lose fat while preserving muscle mass. While semaglutide reduces your appetite, TRT helps build muscle and gives you the energy to make healthier food and exercise choices, says Kohn.
More research is needed on how semaglutide affects testosterone, but Kohn says he doesn’t see a big effect in practice. “We’re not seeing that semaglutide and testosterone interact in such a way that we have to dose adjust,” he says.
Semaglutide might even increase your testosterone over time. When men lose fat, they naturally produce more testosterone because there’s less aromatase activity converting the testosterone into estrogen. “Testosterone is converted to estrogen in peripheral fat,” says Kohn. “So less fat, more of your testosterone in men stays as testosterone and won’t convert to estrogen.”
Over time, some men may even be able to wean off TRT under medical supervision, says Kohn. When you start TRT, your doctor should check your blood levels of testosterone every three to six months. If you’re combining semaglutide with testosterone, they might stick closer to confirming your testosterone every three months, he says.
TRT can help mitigate the muscle loss seen in semaglutide users, says Kohn. One study found that 45 percent of the weight people lost on semaglutide came from lean muscle mass. 8
“You need a certain amount of testosterone to be able to maintain the turnover of your muscles,” says Kohn. “So in theory, people who have low testosterone and take semaglutide experience more of a loss of muscle mass.” Resistance training and a high-protein diet are essential for preserving muscle—whether you’re on TRT, semaglutide, or both, says Lee.
Taking semaglutide and TRT together could also improve your emotional well-being, says Lee. TRT boosts mood on its own, and losing weight while gaining muscle by adding semaglutide could help you feel better about your body.
Semaglutide, TRT, and Erectile Dysfunction
There’s speculation (especially on Reddit) that semaglutide causes ED. But does the science back that up?
Semaglutide affects appetite and satiety, and some men report a drop in libido—possibly because the same neural pathways that regulate hunger also influence sexual desire. “People report a decreased interest in sex, [similar to their] decreased interest in food when they start semaglutide,” says Kohn. “Theoretically, taking testosterone plus semaglutide could help cancel out some degree of that.”
Testosterone is a proven libido booster, but the science of semaglutide and sex is more complicated. Medical records analysis showed that about 1.5 percent of non-diabetic men taking semaglutide had erectile dysfunction (ED)—more than men who didn’t take the weight-loss drug. 9
But semaglutide might help ED in the long run, says Kohn. It improves obesity and cardiovascular health—two factors linked to erectile dysfunction. Since strong blood flow is essential for erections, weight loss could actually help in the long run.
If you experience ED while taking semaglutide, talk to your doctor about adjusting your dose, adding TRT, or temporarily using an ED medication like sildenafil or tadalafil.
Who Shouldn’t Combine TRT and Semaglutide?
You should only use TRT if you have hypogonadism—clinically low testosterone. “If someone has a normal testosterone level and is starting on semaglutide, it would not be advisable to add TRT,” says Kohn.
Here’s why: Your body can only use so much testosterone. If you have a normal amount, adding more doesn’t add benefits, but it does pose the risk of side effects, he says.
TRT is also not recommended if you have heart issues including:
- Uncontrolled heart failure
- A recent heart attack (within six months)
- Untreated high blood pressure
“Patients with other cardiac issues, if well managed, may be treated but require close cardiac monitoring,” says Staheli
TRT may also not be advised if you have sleep apnea. If you have a history of prostate cancer, your doctor will need to monitor you more closely while using TRT, he says. Avoid TRT if you’re planning to expand your family, as it can suppress fertility. 10
Semaglutide is FDA-approved for weight management in people with a body mass index of 30 or higher or 27 or higher with at least one weight-related condition such as high blood pressure or high cholesterol. It’s also approved for type 2 diabetes.
Nearly half of Americans meet this criteria. 11 Taking semaglutide for other conditions, however, could be risky. In one study, off-label use was one of the top factors in adverse event reports about semaglutide. (11) Avoid semaglutide if you have a history of pancreatitis, medullary thyroid cancer, or a family history of thyroid cancer, says Lee.
TRT and semaglutide must be prescribed by a licensed physician who reviews your health first. Both have potential for side effects, but if you’re eligible for both medications, using them together is unlikely to add extra risk, says Lee.
The Bottom Line
If you have low testosterone and need to lose weight, pairing semaglutide and TRT could help. Semaglutide helps you eat less, while TRT provides energy and supports muscle growth. Talk to your healthcare provider about whether this drug combination will be safe and effective for you based on your health history and risk factors.
