Tesamorelin for weight loss: does this peptide work?

Tesamorelin is a peptide that’s been approved to reduce excess abdominal fat in people with HIV. Could this peptide have similar fat-related benefits in a broader population as well? The short answer is: We don’t know. For the longer answer, read on as we explore the possibilities of tesamorelin for weight loss.

Tesamorelin is a prescription medication approved by the US Food and Drug Administration (FDA) to reduce deep belly (visceral) fat in adults with HIV-associated lipodystrophy (a condition that affects how your body stores or loses fat). Some healthcare providers prescribe tesamorelin off-label for body recomposition changes, though evidence for this use outside of HIV is limited. 

Tesamorelin is a synthetic (i.e. man-made) peptide and growth hormone-releasing factor analog. Meaning, it stimulates your pituitary gland to produce more human growth hormone. 

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Not exactly, no. Tesamorelin can decrease both visceral belly fat and waist circumference. However, it does not typically reduce total body weight. These effects have been primarily studied in people with HIV-related lipodystrophy.  

The prescribing information for tesamorelin specifically states that it is not approved for weight loss because it has a “weight neutral effect.” 

In two 26-week clinical trials, weight changes were negligible in both the tesamorelin and placebo groups. 

• In one study, people taking tesamorelin lost about 0.9 pounds, while those on placebo had no change in body weight. 

• In the other, people taking tesamorelin gained about 1.1 pounds, compared with about 0.7 pounds in the placebo group.  

• Neither difference was statistically significant. 

Tesamorelin should not be considered a weight loss medication, says Manu Sehgal, MD, an internal medicine and geriatrics physician. “When used correctly in the appropriate patient, tesamorelin has been shown to specifically reduce visceral fat (the fat that accumulates around the internal organs) rather than the total body weight.” 

Tesamorelin does not generally cause weight loss. But it can change body fat distribution by reducing visceral fat while helping to maintain lean muscle.  

Here’s how tesamorelin works, based on studies of people with HIV:

• Encourages your body to release more growth hormone naturally. Growth hormone, in turn, helps increase lean muscle mass while decreasing belly fat.

• Helps break down visceral fat. This is the deeper fat that wraps around your organs and increases your risk of fatty liver disease and metabolic syndrome. Losing this kind of fat can lower some of the cardiometabolic risk factors associated with obesity, Dr. Sehgal says.

• Helps to maintain — or increase — the percentage of lean muscle. Preserving muscle mass supports a healthier metabolism, leading to faster calorie burning, and can help you stay physically active, which in turn supports further weight loss.

Thanks to how tesamorelin works, it can lead to dramatic improvements in your waistline — even if you lose little body weight, or none at all, Dr. Seghal says. 

Tesamorelin has been approved since 2010 for reducing excess belly fat in HIV-positive adults with lipodystrophy. It is not recommended for weight loss, and its safety has not been well-studied in people without HIV. 

While tesamorelin can be an effective treatment for lipodystrophy, it can cause serious side effects and should not be taken by people who:

• Are pregnant

• Have cancer or are undergoing cancer treatment

• Have hypothalamic-pituitary axis (HPA) dysfunction for reasons such as former pituitary surgery, radiation to certain areas of the head, or head trauma 

Tesamorelin side effects and risks

The most common side effects of tesamorelin include:

• Injection site reactions (e.g. redness, itching)

• Pain in the arms or legs

• Joint pain

• Muscle pain

• Peripheral edema (swelling in the hands, arms, legs, ankles, or feet)

Tesamorelin may also cause serious side effects, including:

• Fluid retention, which can present as swelling, muscle pain, and carpal tunnel syndrome

• Serious allergic reactions

• Increased risk of neoplasms (abnormal tissue growths), especially in people with a history of cancer

• Increased risk of diabetes

• Increased risk of death in people who are critically ill as a result of open-heart surgery, abdominal surgery, trauma, or acute respiratory failure 

There is no officially recommended dosage of tesamorelin for weight loss, since the drug is not approved for weight loss. 

When used for reducing belly fat in people with HIV-related lipodystrophy, the recommended dose is 1.28 mg daily (as brand-name Egrifta WR). Tesamorelin is administered once daily via subcutaneous (under-the-skin) injection into the abdomen, rotating injection sites.  

Here are the main things to keep in mind when considering tesamorelin for weight loss:

• It hasn’t been shown to drive weight loss. While tesamorelin can help reduce belly fat and inches off your waistline, that may not translate into pounds on the scale, according to existing research.

• Its fat loss benefits have been primarily studied in people with HIV. While tesamorelin shows promise, more research is needed before any conclusions can be drawn about its effectiveness for fat loss in people without HIV.

• It can affect your blood sugar. Growth hormone secretagogues like tesamorelin can worsen insulin resistance and blood sugar control, which can be risky for people with diabetes or prediabetes, Dr. Sehgal explains. 

• It requires close monitoring. Because tesamorelin carries serious risks and side effects, Dr. Sehgal says it’s safest when used under close medical supervision, especially if you have a history of cancer or other serious medical conditions.

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There are multiple FDA-approved alternatives to tesamorelin for weight loss, from weight loss-specific GLP-1s and other pills to evidence-based lifestyle changes. What’s more, they all have stronger safety profiles and weight loss results than tesamorelin. (Likely because, again, tesamorelin has been shown to have a “weight neutral effect.”)

GLP-1 medications for weight loss

Glucagon-like peptide 1 receptor agonists — or GLP-1s — are prescription medications that target hormones in the body that help control appetite, satiety (aka fullness), and blood sugar. More specifically, they work by slowing digestion and sending fullness signals to the brain, helping you feel satisfied sooner, stay full longer, and experience fewer cravings.

Injectable GLP-1s approved for weight loss include: 

• Wegovy (semaglutide), which led to an average weight loss of about 15% on the standard 2.4 mg dose in 68 weeks, and up to about 19% on the higher 7.2 mg dose in 72 weeks.

• Zepbound (tirzepatide), which targets GLP-1 and  GIP (another hormone) and led to an average weight loss of about 20% in 72 weeks. 

• Saxenda (liraglutide), which led to an average weight loss of about 8% over 56 weeks. 

Like tesamorelin, these medications are injected subcutaneously (under the skin). Wegovy and Zepbound are administered weekly, while Saxenda is taken daily (also like tesamorelin). 

Oral GLP-1s approved for weight loss include:  

• Wegovy pill (semaglutide), which produced an average weight loss of ~14% in 64 weeks. 

• Foundayo (orforglipron), which produced an average weight loss of 7.5%--11.2% in 72 weeks. 

Both GLP-1 tablets are taken daily, but only Foundayo can be taken any time, with or without food. (The Wegovy pill administration must be taken on an empty stomach with water, and requires waiting at least 30 minutes before eating, drinking, or taking other medications.) 

Other weight loss pills

In addition to GLP-1s, there are other FDA-approved weight loss medications that can also help you reach your goals. Keep in mind, though, that each of these prescription drugs works differently and generally produces less weight loss than GLP-1s. Still, they may be a fit for you, depending on your other health conditions and your healthcare provider’s assessment. 

So, here are a few non-GLP-1 weight loss pill options: 

• Qsymia (phentermine-topiramate), which led to an average weight loss of about 8%–11% within a year, depending on the dose.  

• Contrave (naltrexone/bupropion), which led to an average weight loss of about 5%–6% within a year. 

• Xenical (orlistat), which led to an average weight loss of about 6%–10% within a year. 

Lifestyle changes

Finally, it’s possible to lose at least 5% of your body weight by implementing lifestyle changes alone. Depending on your current body weight and health situation, experts may recommend a combination of:

• Reducing your caloric intake to about 1,200–1,500 calories daily for most women, and about 1,500–1,800 for most men (though speak with your healthcare provider for an individualized recommendation)

• Getting at least 150–200 minutes of aerobic exercise weekly, plus two (or more) resistance-based workouts

• Setting goals and tracking your weight loss progress

• Making other healthy lifestyle changes, such as managing stress and improving your sleep

“Sleep is one of the most powerful contributors to visceral fat accumulation,” Dr. Sehgal says. 

Instead of trying tesamorelin, he recommends doing an experiment: “Take your waist measurement every two weeks for two months and optimize sleep.” 

By simply focusing on improving your sleep quality, you may notice significant improvements in your belly fat, Dr. Sehgal says. 

The research backs him up. In a study of a year-long weight loss program, participants who got better sleep also lost more weight and fat overall. That being said, sleep optimization works best as part of a broader lifestyle approach that includes diet and exercise, not as a standalone strategy.

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While tesamorelin is technically a peptide like popular GLP-1s (e.g. Wegovy, Zepbound), it belongs to a completely different drug class and works in a very different way. It’s not approved — or really that effective — for weight loss. That said, the drug is known to reduce belly fat and waist circumference in people with HIV-related lipodystrophy. 

Here’s what to remember before bringing up this peptide to your healthcare provider:

• Tesamorelin works by telling the body to release more growth hormone, which can have positive effects on fat burning, metabolism, and lean muscle mass. It’s what’s known as a growth hormone secretagogue.

• While tesamorelin may help you shed excess belly fat and a few inches off your waistline, it doesn’t cause weight loss. Plus, nearly all the evidence on its body recomposition effects comes from studies of adults with HIV-related lipodystrophy. 

• In addition to research being almost exclusively limited to people with  HIV, tesamorelin can carry serious side effects, including an increased risk of diabetes and cancer. When used for its FDA-approved indication (and as prescribed by your provider!), the benefits may outweigh the risks, but close medical supervision is important.   

• When it comes to weight loss, there are other proven and approved alternatives to tesamorelin with stronger evidence for reducing body weight. These include oral and injectable GLP-1s, other prescription weight loss pills, and certain lifestyle changes.