Best Peptides for Weight Loss

Increasingly more people are turning to therapeutic peptides to shed weight. Around 12% of adults have taken a particular category of weight loss peptides called glucagon-like peptide-1 receptor agonists (GLP-1 RAs), and combined sales of the most popular GLP-1 RAs have grown by 89% since 2022.1 2 The media has reflected this market expansion, with advertisements for brands like Ozempic and Mounjaro playing in practically every commercial break.

Because commercials can tell you only so much, you need other resources to see whether a particular treatment is the one for you. This guide to the best peptides for weight loss integrates all of the most valuable information on the topic — on GLP-1 RAs as well as non-GLP-1 alternatives — to help steer you toward the right decision for your health.

For the quickest rundown of our findings, here is a handy summary of recommendations directly below. Then you can read through the rest of the guide to understand how we made our selections.

Over the past two decades, Innerbody Research has helped tens of millions of readers make more informed decisions about staying healthy and living healthier lifestyles.

In the years since we started covering weight loss peptides, we’ve actively monitored the space and gained a great deal of knowledge on their therapeutic potential. So far, our cumulative research encompasses several hundred scientific papers and over 1,000 hours. Like the peptide space itself, our efforts are ever-growing.

Our team has also built relationships with medical providers who prescribe weight loss peptides, giving us a closer view of the medicine’s effects on users than you can find from other sources.

Additionally, like all health-related content on this website, this guide was thoroughly vetted by one or more members of our Medical Review Board for accuracy and will continue to be monitored for updates by our editorial team.

We evaluated the market’s best weight loss peptides based on three criteria that are likely to guide your health choices:

• Effectiveness: Which peptide has the most robust scientific evidence to support its utility for weight loss?
• Safety: Among peptides with similar side effect profiles, which one poses the least risk?
• Availability: Which peptide is the most readily accessible through multiple channels?
• Ease of use: Are there any viable non-injectable alternatives?

Here’s how our three recommendations performed in each category:

Effectiveness

Winner: Tirzepatide

The scientific literature points to tirzepatide and semaglutide as the two most effective peptide categories for weight loss. Between them, tirzepatide is the more effective option for its dual mechanisms of action. Two recent studies make clear its superiority.

The first, published in 2021 in The New England Journal of Medicine, was a 40-week phase 3 trial involving a large sample size of 1,973 patients with type 2 diabetes. The patients were randomized into four groups: three received different doses of tirzepatide — 5, 10, and 15mg per week — and the fourth received 1mg semaglutide. By the study’s end, patients in all three tirzepatide groups lost around 4-12 more pounds than the semaglutide group and exhibited better diabetic biomarkers.3

The second was published in JAMA Internal Medicine in 2024. It was a cohort study that examined 18,386 patients with overweight or obesity (mean baseline weight: 242lb) who received tirzepatide or semaglutide between May 2022 and September 2023. The study concluded that tirzepatide was associated with “significantly greater weight loss than semaglutide.”4

Don’t take these findings to mean that semaglutide is drastically inferior to tirzepatide. Far from it. You’ll see later, in its dedicated section, just how potent semaglutide is for weight loss. You’ll also see, in another section, why you may want to consider an alternative like tesamorelin instead.

Safety

Winner: Semaglutide

GLP-1 RAs in general have a lower side effect risk than tesamorelin, and the literature currently favors semaglutide’s safety profile above that of tirzepatide.

The two GLP-1 receptor agonists covered in this guide have common side effects — nausea, diarrhea, and vomiting — but in the 2021 study we’ve referenced, semaglutide exhibited up to a 5% lower risk of nausea, 4% of diarrhea, and 2% of vomiting.3 Its lower side effect risk compared to tirzepatide is slight but clear.

With tesamorelin, the most likely adverse events, according to the clinicians we know, are mild flu-like symptoms such as fatigue, headache, and nausea, but it’s also associated with an increased risk of cancer owing to its activity on growth hormone5 — certainly more worrisome than the gastrointestinal problems linked to GLP-1 RAs. We cover tesamorelin’s cancer risk in greater detail in a later section, “How safe are peptides for weight loss?”

Availability

Winner: Semaglutide

When we say semaglutide is the most widely available weight loss peptide, we mean you can more easily get a prescription through multiple channels.

We’ll illustrate with an example. Say that you want to try tesamorelin. For a prescription, you have little choice but the traditional route — schedule an appointment with your doctor, get the script through them, and get it filled at a pharmacy. But if you wanted semaglutide instead, you could go through any one of the numerous online telemed platforms that carry medical-grade weight loss peptides. A quick accounting shows there are at least nine reputable platforms to choose from:

• Eden
• Mochi
• Zealthy
• Plush
• Ivy Rx
• Henry Meds
• Hims/Hers
• Ro
• Strut

Tirzepatide is available through telemed, too, just not as many platforms as semaglutide. Only the first six of the nine companies above carry the more potent peptide.

Ease of use

Winner: Semaglutide

Therapeutic peptides are typically injectable medications that you have to reconstitute from powder and store in cold conditions. Hardly the picture of convenience. Fortunately, oral weight loss peptides are available, including easy-to-swallow drops, giving the needle-averse among us access to a world of powerful weight loss medications.

And most of them are for semaglutide.

Looking again at the nine reputable telemed platforms we’ve mentioned, we find that seven of them have oral versions of semaglutide:

• Eden
• Mochi
• Zealthy
• Plush
• Ivy Rx
• Henry Meds
• Strut

Meanwhile, only three carry oral tirzepatide — Zealthy, Henry Meds, and Strut.

So, if oral administration is a must-have for your peptide-assisted weight loss, then you’ll have an easier time finding a semaglutide treatment than a tirzepatide one. (Tesamorelin, by the way, isn’t readily available as an oral medication.)

Please know that ease of use comes at the cost of effectiveness. In a later section, “Injectable vs. oral weight loss peptides,” we discuss how much more effective injectables are compared to non-injectable alternatives.

Before we get into the finer scientific details, take a look at this table comparing our three recommendations across key characteristics:

Peptides are chains of amino acids that are essential for metabolism, wound repair, inflammation control, and innumerable other biochemical processes.6 They occur naturally but can also be synthesized in a lab to resemble the ones in your body. Those synthetic variants are called therapeutic peptides because they serve specific healing purposes, such as weight loss.

Weight loss peptides fulfill their purpose by mimicking the hormones responsible for regulating your appetite and metabolizing fat. How they go about their mimicry depends on what category of peptides they belong to.

In the following subsections, we discuss three peptide categories that are known to cause weight loss. In each case, your weight loss depends on continued compliance with therapy, and you can expect weight to return after you stop treatment.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs)

Semaglutide and tirzepatide are examples of GLP-1 RAs, a category of peptides originally developed for diabetes management but found to promote weight loss through their actions on the pancreas and digestion. The “GLP-1” part of the name refers to a naturally occurring hormone in the gut that participates in a broad array of physiological functions. Among other things, it:7

Glucose-dependent insulinotropic polypeptide (GIP) receptor agonists

In addition to being a GLP-1 RA, tirzepatide is also an agonist of GIP, a gut hormone that impacts glucose and fat metabolism.13 It’s similar to GLP-1 in that it stimulates insulin secretion from the pancreas, and research shows that the two hormones work synergistically to increase weight loss. But apart from its action on insulin, GIP is also believed to improve the body’s long-term lipid storage such that it reduces fat accumulation in the skeletal muscles and organs.14 This dual activity is likely what accounts for tirzepatide’s superlative efficacy for weight loss in clinical studies.

Growth hormone secretagogues

A growth hormone secretagogue, such as tesamorelin, is a compound that causes the body to increase its growth hormone levels. Tesamorelin, specifically, is an analog of growth hormone-releasing hormone (GHRH), so it mimics a precursor hormone that stimulates growth hormone secretion.

Besides affecting almost every tissue and organ, growth hormone promotes physical growth and normal metabolism.15 16 Its metabolic effects relate to its ability to stimulate the production of yet another hormone, insulin-like growth factor-1 (IGF-1). It happens that low IGF-1 levels correlate with high body fat composition, so elevating IGF-1 via growth hormone can facilitate fat loss.17

Therapeutic peptides are usually administered by subcutaneous injection (a needle), to ensure the maximum amount of medicine enters your bloodstream to take effect. But oral alternatives — dissolving tablets, drops, troches — are available from some of the leading telemed providers. So, with the availability of a less invasive delivery system, why does subcutaneous injection remain the standard route of administration?

The answer comes down to bioavailability, or the amount of medicine your body actually absorbs. Injected subcutaneously, a peptide can yield a bioavailability of up to 50%, which is worlds above the sub-1% you might get from an orally ingested alternative.18 19 The reason for such a large disparity is that orally ingested peptides must pass through your digestive tract, where they can easily degrade, and peptide molecules are often too large to pass easily through your intestinal lining.19 It’s true there are oral peptides that leverage absorption-enhancing technologies, but even with them you’re getting maybe just a bit closer to 2% bioavailability — little improvement over non-enhanced forms.20 It’s also true that orobuccal administration (through the linings of the mouth) provides a much more bioavailable route than ingestion, but even through that route the relative absorption is less than half that of subcutaneous injection.37

Things being as they are, if you want to get the most out of your (expensive) peptide therapy for weight loss, subcutaneous injection is the way to go — at least until the technology improves enough to raise oral alternatives to the same level of absorptiveness.

Therapeutic peptides are generally safe for people with indicated health problems. Part of that is because you ought to undergo a medical exam and laboratory tests to validate your candidacy for a peptide before you can get a prescription, and the tests function as a first-line failsafe against contraindications. (We say “ought to” because it’s possible to get a GLP-1 RA prescription with no more than a brief appointment — no exam or labs. If that’s how your consultation goes, we recommend asking follow-up questions to help ensure your medical history properly indicates a weight loss peptide.)

Another part is that the most likely side effects are mild. With GLP-1 RAs, you might experience nausea, diarrhea, or vomiting;3 with tesamorelin, it’s flu-like symptoms; and with injectable peptides broadly, there’s a risk of transient injection-site reactions such as pain, itching, swelling, or redness.21

Severe side effects are possible but rare. Among our recommendations, the most serious one is the elevated cancer risk associated with growth hormone secretagogues like tesamorelin. The risk stems from the ability of growth hormone secretagogues to stimulate cell death and replication, two biological events that precede cancer development.5 So if you currently have cancer or have survived a cancer diagnosis, you would not be indicated for tesamorelin or any other peptide in its category. Your exam and lab tests should screen you out of candidacy.

Medical-grade vs. research-grade peptides for weight loss

Many of the therapeutic peptides you can find online are research-grade peptides, designed to be applied in laboratory settings but not to be consumed by humans. They’re available for purchase without a prescription, but because they aren’t subjected to the same purity and safety rigors as their medical-grade counterparts, they’d pose a significant health risk if you were to inject them into your body.

It’s crucial, then, that you use medical-grade products for your weight loss goals. You can get a prescription through your physician or one of the reputable telemed platforms we’ve discussed in this guide (e.g., Henry Meds, Hims/Hers). But keep in mind that, of the three peptides discussed in this guide, reputable telemed platforms carry only tirzepatide and semaglutide at this time. If tesamorelin is what you want, you’ll have to arrange a visit with your physician.

To be a candidate for a weight loss peptide, namely a GLP-1 RA, you typically need to meet one or several of the following diagnostic criteria:

• Obesity: Obesity is defined as having a body mass index (BMI) above 30 (e.g., someone who’s 5’11” and weighs 215lb would qualify as obese),22 but a BMI slightly below 30 doesn’t disqualify you for a peptide prescription.
• Weight-associated health problem: Several health problems stem from carrying excess body weight, including but not limited to type 2 diabetes, cardiovascular disease, hypertension, and sleep apnea. Any one of those health problems, in addition to overweight or obesity, might indicate you for a weight loss peptide.

For tesamorelin, the diagnostic criteria can be broader. Strictly speaking, it’s indicated for people with HIV who’ve accumulated abdominal fat as a result of antiretroviral therapy, but clinicians prescribe it off-label to non-HIV patients who want to shed abdominal fat of their own.

Who are they not for?

Even if you meet the diagnostic criteria we’ve discussed, you would not be indicated for a weight loss peptide if you are:

Most scientifically supported peptide for weight loss

Tirzepatide is a dual agonist, which means it simulates the activities of not one but two hormones:

• GLP-1: stimulates insulin secretion, inhibits glucagon secretion, slows digestion, and increases feelings of fullness7
• GIP: stimulates insulin secretion and helps to reduce fat accumulation14

Thanks to tirzepatide’s two-part action against obesity factors, it has risen to the top of the hierarchy among all therapeutic peptides currently used for weight loss.

It’s even better than its more widely available cousin, semaglutide, as shown by several large-scale studies. A good example is a trial from 2021 that involved 1,973 patients with diabetes. The patients were randomized to receive either semaglutide or one of three doses of tirzepatide. After 40 weeks, all three tirzepatide groups lost 4-12 more pounds, on average, than the semaglutide group and came out with healthier diabetic biomarkers.3 Another example is a massive cohort study of 18,386 patients, which found that tirzepatide patients lost 5-15% more weight than their semaglutide counterparts.4

Specific side effects of tirzepatide

The most common side effects of tirzepatide are nausea, diarrhea, and vomiting. It’s the same as with semaglutide, except tirzepatide’s superior dual-agonist efficacy seems to correspond to a higher side effect risk. In the 2021 trial of 1,973 patients, tirzepatide led to a 2-5% greater incidence of these gastrointestinal adverse events.3

Most accessible peptide for weight loss, with a lower side effect risk

Semaglutide may not have the double-duty action of tirzepatide, but it’s still a highly effective treatment for achieving rapid weight loss. As a GLP-1 receptor agonist, it targets receptors in your body, including in your pancreas, that are responsible for regulating how full you feel after a meal, and it slows the rate at which food leaves your stomach.24 The result is that you’re likely to eat less than you normally would, so you avoid the excess calories that your body would otherwise store as fat. Such were the outcomes of a 2017 study of 30 subjects with obesity, who not only exhibited “less appetite and food cravings” but also “better control of eating and lower relative preference for fatty, energy‐dense foods.”25

Other studies can help us quantify the extent to which semaglutide can aid in weight loss. Take, for example, a 2022 trial of 338 participants that compared its effects to those of another GLP-1 RA, liraglutide. Here, after 68 weeks, the semaglutide group saw an average 15.8% reduction in body weight from baseline, as opposed to the 6.4% reduction with liraglutide.26

So, while semaglutide is less clinically effective than tirzepatide, it’s a demonstrably excellent GLP-1 solution for weight loss. It’s also more widely available than tirzepatide. At least nine reputable telemed platforms sell it:

• Eden
• Mochi
• Zealthy
• Plush
• Ivy Rx
• Henry Meds
• Hims/Hers
• Ro
• Strut

In comparison, only the first six platforms carry tirzepatide.

Specific side effects of semaglutide

Semaglutide’s most common side effects are the same as tirzepatide’s: nausea, diarrhea, and vomiting. But the effects are usually less prevalent, likely owing to semaglutide’s comparably milder mechanism of action.3 If you have a sensitive stomach, then semaglutide might be the better weight loss peptide for you.

Best non-GLP-1 peptide for moderate weight loss

Tesamorelin is an off-label prescription for weight loss. That means it’s FDA-approved for a separate health condition but has uses that make it effective for other ends.

Its FDA-approved use is for treating HIV-associated lipodystrophy, or excess abdominal fat accumulation resulting from antiretroviral therapy, and it has fared well in its specialty. In a 2010 clinical trial, for example, subjects who received tesamorelin ended with an average 18% decrease in visceral fat compared to placebo.27 This fat-reducing quality is what makes tesamorelin an attractive non-GLP-1 peptide option. It may be especially appealing to people who prefer a more moderate approach to body recomposition so as to avoid the sunken facial features (a.k.a. “Ozempic face”) that attend rapid weight loss.28

Though most tesamorelin research has looked at patients with HIV, at least one study from 2006 points to its utility for non-HIV-positive users. In it, a group of Japanese participants was randomized into either a tesamorelin group or a placebo group. After 24 weeks, the tesamorelin group saw an average 9.3% decrease in body fat, as well as improved serum lipid profiles.29

Other researchers have highlighted tesamorelin’s potential for improving tangential areas of health. For example, a 2019 study found it to be “effective in increasing skeletal muscle area and density.”30

Specific side effects of Tesamorelin

Tesamorelin can cause flu-like symptoms such as fatigue, nausea, and headache. Joint and muscle pain, of varying intensities, may also occur. These effects are usually mild and more typical at the start of treatment. Their likelihood decreases as you continue with your protocol.

Among people with an existing cancer diagnosis, as well as those who’ve recovered from cancer, growth hormone secretagogues in general can worsen their prognosis or elevate the risk of recurrence.5