Peptides for the Treatment of Obesity: An Update on Clinical Findings

With weight-related diseases at an all-time high, controlling body weight is becoming increasingly important. While we know that physical activity and mindful diet choices can promote fat loss, the emergence of the weight loss peptide, semaglutide, has popularised a new way of managing weight. By altering the activity of specific receptors in the body, researchers have discovered that they can induce metabolic states and promote certain behaviours. Whether this is the healthiest option for most people is questionable, but the efficacy of these drugs makes them an attractive option.

As fascinating as these new peptides may be, each one must undergo a rigorous set of tests to ensure that they are safe and effective. In vitro studies allow us to see how drugs affect cells and enzymes outside of the body. Animal, or in vivo studies, can give us some idea of how a drug works in a living organism. Clinical studies tell us what they actually do in humans. These are the riskiest but most valuable tests we can perform and are required before approving a drug.

This article highlights some of the results from clinical trials of yet unapproved weight loss peptides.

Retatrutide

Retatrutide is being investigated for its ability to manage weight, treat type 2 diabetes (T2D) and improve fatty liver disease. It acts on GLP-1, GIP and GCG receptors to reduce hunger, promote the burning of fat and regulate blood glucose levels.

A phase 2 trial on people with a body mass index (BMI) of over 30 found that after 48 weeks, participants taking 12 mg once per week lost an average of 24.2% of their body weight. Even just 1 mg per week of retatrutide was able to produce a 8.7% reduction in weight, which was higher than the 2.1% weight reduction seen in the placebo group¹.

Another phase 2 trial was conducted on participants with T2D. After 36 weeks, participants who had been taking an escalating dose up to 12 mg per week experienced an average weight loss of 16.94%. This study found that a dose of 4 mg per week was required to produce significant weight loss results. In addition to this, glycaemic control was improved².

A phase 2 trial looking at retatrutide’s ability to treat fatty liver disease was conducted, with the amount of liver fat being assessed after 24 weeks. 1 mg of retatrutide per week reduced liver fat by 42.9%, with the efficacy of the drug increasing with dose. Doses of 8 and 12 mg reduced liver fat by 81.4% and 82.4%, respectively³.

Although retatrutide and other GLP-1 receptor agonists reduce body weight, they can also cause the loss of other tissues. A study that looked at body composition over 36 weeks of treatment found that it was mostly fat that was lost, with only a small loss of lean mass⁴.

So far, results suggest that retatrutide is a powerful peptide, able to potently promote weight loss. In all of these studies, participants most commonly complained of gastrointestinal disturbances such as nausea, diarrhoea, vomiting and constipation.

Cagrilintide

This peptide is an analogue of amylin. Amylin is a hormone produced mainly by the beta cells of the pancreas that helps to control food intake by influencing satiety. It has been paired with semaglutide, an approved GLP-1 receptor agonist, for the treatment of obesity and T2D in clinical trials. This combination of cagrilintide and semaglutide is named CagriSema.

A phase 2 clinical trial looking at CagriSema treatment for T2D found that the peptides could improve glycaemic control and significantly improve weight loss when compared to treatment with semaglutide or cagrilintide alone. CagriSema could also improve HbA_1C more effectively than cagrilintide, although it did not outperform semaglutide monotreatment⁵.

A phase 3a, 68-week clinical trial was conducted to assess CagriSema and its effect on people with a BMI of 30 or more who did not have T2D. Participants were given a dose of 2.4 mg semaglutide and 2.4 mg cagrilintide together, which produced an impressive weight reduction of 20.4%.

Overall, CagriSema appears to effectively reduce body weight. Although it may not lower HbA_1C to as great an extent as semaglutide alone, it still offers a significant improvement in blood sugar control⁶.

Pemvidutide

The peptide Pemvidutide is a GLP-1 and GCG dual receptor agonist currently being investigated for its efficacy at treating fatty liver disease and obesity.

In one clinical study, patients with a BMI of more than 28 were given 1.2 to 2.4 mg of pemvidutide weekly for 12 weeks. A reduction in liver fat content of up to 68.5% was seen in participants who were given the dose of 1.8 mg⁷.

Another study on patients with metabolic dysfunction-associated steatohepatitis (MASH) and fibrosis of the liver found that resolution of MASH was achieved in just over half of the participants taking pemvidutide, while a third saw improvements in fibrosis⁸.

Mazdutide

Mazdutide, like pemvidutide, is a GLP-1 and GCG dual receptor agonist. It is approved for the management of weight and T2D in China, but is not yet approved elsewhere. It has been tested on Chinese patients with obesity and T2D.

In studies on participants who were obese but did not have T2D, mazdutide has been found to reduce weight in a dose-dependent manner. A study lasting 48 weeks found that people taking 6 mg of mazdutide per week achieved an average weight loss of 14.01%, with almost half of this group achieving at least a 15% reduction in weight⁹.

Even higher doses have been tested in an escalation study, where participants took doses of mazdutide that gradually increased to 16 mg per week over the course of 20 weeks. In this study, approximately 75% of participants lost at least 15% of their body weight¹⁰.

For those with T2D, higher doses produced the greatest improvements in blood glucose control. After 24 weeks, participants taking 6 mg per week saw reductions of 2.15% in their HbA_1C and lost 7.81% of their body weight¹¹.

The most common adverse events associated with mazdutide were diarrhoea, decreased appetite and nausea¹².

AMG 133 (maridebart cafraglutide)

This peptide is a fully human monoclonal anti-human GIPR antagonist antibody conjugated to two GLP-1 analogue agonist peptides. Although other weight loss peptides aim to agonise GIP receptors, the antagonism of GIP by AMG 133 is intended to reduce the negative effects associated with GIP activation while stimulating weight loss by activating GLP-1 receptors.

In a phase 1 study, single doses of 21 and 840 mg resulted in 1.6% and 2.8% reductions in body weight after 6 days, respectively. Reductions in weight continued over time. When given as multiple doses, by day 85, a reduction in body weight of 14.5% was experienced by participants who were administered 420 mg¹³.

A phase 2 study has also been conducted on obese and diabetic participants. Doses of 140 to 420 mg were given subcutaneously every 4 weeks. After 52 weeks, obese participants lost 12.3 to16.2% of their body weight, while obese and diabetic participants lost between 8.4 and 12.3%. A reduction of up to 1.6% in HbA_1C was observed¹⁴.

Adverse events were mainly GI-related, including nausea and vomiting and were mild in severity. Participants who took escalating doses experienced these negative effects less frequently.

Conclusion

These are just a few examples of some weight loss drugs currently being investigated in clinical trials. Researchers are continuously coming up with new solutions to problems and finding novel ways to use old drugs; as such, this list is far from exhaustive. It is particularly fascinating to see that both GIPR agonism and antagonism, when combined with GLP-1R agonism, can result in weight loss.

Clinical trials give us some of the most reliable data on how safe and effective a drug is and are necessary before approval can be granted. Since all of these drugs are already undergoing clinical trials, we may soon see some of them being prescribed as weight loss drugs.

References

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Rosenstock J, Frias J, Jastreboff AM, et al. Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes: a randomised, double-blind, placebo and active-controlled, parallel-group, phase 2 trial conducted in the USA. Lancet Lond Engl. 2023;402(10401):529-544. doi:10.1016/S0140-6736(23)01053-X
Sanyal AJ, Kaplan LM, Frias JP, et al. Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease: a randomized phase 2a trial. Nat Med. 2024;30(7):2037-2048. doi:10.1038/s41591-024-03018-2
Coskun T, Wu Q, Schloot NC, et al. Effects of retatrutide on body composition in people with type 2 diabetes: a substudy of a phase 2, double-blind, parallel-group, placebo-controlled, randomised trial. Lancet Diabetes Endocrinol. 2025;13(8):674-684. doi:10.1016/S2213-8587(25)00092-0
Frias JP, Deenadayalan S, Erichsen L, et al. Efficacy and safety of co-administered once-weekly cagrilintide 2·4 mg with once-weekly semaglutide 2·4 mg in type 2 diabetes: a multicentre, randomised, double-blind, active-controlled, phase 2 trial. Lancet. 2023;402(10403):720-730. doi:10.1016/S0140-6736(23)01163-7
Garvey WT, Blüher M, Osorto Contreras CK, et al. Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2025;393(7):635-647. doi:10.1056/NEJMoa2502081
Harrison SA, Browne SK, Suschak JJ, et al. Effect of pemvidutide, a GLP-1/glucagon dual receptor agonist, on MASLD: A randomized, double-blind, placebo-controlled study. J Hepatol. 2025;82(1):7-17. doi:10.1016/j.jhep.2024.07.006
Noureddin M, Harrison SA, Loomba R, et al. Safety and efficacy of weekly pemvidutide versus placebo for metabolic dysfunction-associated steatohepatitis (IMPACT): 24-week results from a multicentre, randomised, double-blind, phase 2b study. Lancet. 2025;406(10520):2644-2655. doi:10.1016/S0140-6736(25)02114-2
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Bhattachar SN, Tham LS, Li Y, et al. Mazdutide reduces body weight in adults with overweight or obesity: A high-dose Phase 1 trial. Diabetes Obes Metab. 2025;27(11):6460-6469. doi:10.1111/dom.70040
Zhu D, Zhao J, Cai H, et al. Mazdutide versus placebo in Chinese adults with type 2 diabetes. Nature. 2026;652(8108):174-180. doi:10.1038/s41586-025-10026-w
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Which SARM is the best for muscle gain?

It can be difficult to determine which SARMs are best for lean muscle building because different body types respond differently to them. Almost all SARMs boost muscle gain, but some have a stronger effect than others.

Top-tier SARMs for muscle gain include:

Test RAD-140
Ibutamoren MK-677
Ostarine MK-2866

Compared to some other brands, they also offer really good performance. RAD-140, Ostarine, and MK-677 are well-known for boosting muscle growth explosively and making gaining muscle much easier.

If you want to gain a lot of muscle quickly, consider using one of the above SARMs.

Do SARMs have side effects?

SARMs’ side effects are generally fewer and less serious than those of anabolic steroids. Still, using SARMs supplement products does have a small risk of complications.

Some side effects that have been reported include:

Diarrhoea
Headaches
Hypertension
Heart disease
Aggression
Acne

It is important to remember that the severity and presence of a side effect will likely depend on both dosage and the specific SARM taken.

Why should I use SARMs?

Burning fat
Bulking or cutting
Improving performance
Decreased recovery time
Building lean body mass
Increasing bone density

What are SARMs?

SARMs, or selective androgen receptor modulators, are relatively new drugs that attach to your body’s androgen receptors, triggering changes in your DNA, which in turn increases your muscles’ ability to grow. Unlike steroids, they target specific types of tissues and don’t come with side effects like breast growth in males.

They combat muscle loss caused by age, osteoporosis, disease, and building muscle and bone. Due to their ability to improve strength with fewer side effects than steroids, dietary supplement brands have started selling them to athletes.

Because they’re anabolic agents that enhance performance, SARMs are on the World Anti-Doping Agency’s list of prohibited substances.

What should I consider before I buy SARMs in the UK?

Before you buy SARMs in the UK, it’s important to consider factors such as product purity, third-party testing, and supplier transparency. UK SARMs is committed to providing high-quality research compounds with clear labelling and lab reports available. Always ensure you’re purchasing from a trusted source that complies with UK regulations.