What do the Results of the Latest Phase 3 Trials Say About Retatrutide? - High-Quality UK SARMs | #1 SARMs Supplier

The results of Phase 3 trials for retatrutide have recently been announced. One of these studies followed patients over the course of 80 to 104 weeks and reported huge weight loss results and improved markers of cardiovascular disease, while another looked at its ability to treat type 2 diabetes. This article will cover how retatrutide is different from other GLP-1RAs and look at the results of these latest studies in greater detail.

What is Retatrutide?

Retatrutide is a peptide that, like semaglutide and other similar weight loss peptides, mimics the action of incretins such as GLP-1. But unlike the first GLP-1RAs, retatrutide targets two additional receptors to enhance its weight loss effects.

One of the best-known examples of a GLP-1RA is semaglutide, sold under the trade name Ozempic. Semaglutide targets only the GLP-1 receptor, bringing about a reduction in appetite and enhancing insulin secretion, leading to improved blood glucose regulation and body weight reduction. Other receptor targets commonly include GIP and GCG, although there are other receptor targets. GIP receptor agonism reduces body weight and appetite independently of GLP-1R signalling¹, while GCG increases energy expenditure and appetite².

These receptors are the targets of numerous drugs aimed at reducing body weight and researchers have investigated the effects of targeting different numbers and combinations of these receptors with varying degrees of success.

Retatrutide is one of the first weight loss peptides that targets GLP-1, GIP and GCG receptors. It is able to bind to GIP receptors with almost 9 times greater affinity than the endogenous hormone, while its affinity for GLP-1R and GCGR is lower than that of their corresponding hormones.

Previous Trials

Just as commonly prescribed GLP-1RAs reduce appetite, so does retatrutide. It can alter people’s attitudes towards eating, reducing the tendency to overeat and overall food intake³.

In some of the earlier trials done on retatrutide, obese patients lost up to 24.2% of their body weight when taking a 12 mg dose⁴.

In patients with type 2 diabetes, a reduction of 2.02% in HbA_1C after 24 weeks and body weight reduction of 16.94% after 36 weeks were recorded in the group taking 12 mg⁵.

In patients with metabolic dysfunction associated steatotic liver disease, an 82.4% reduction in liver fat was seen by 24 weeks in patients taking 12 mg retatrutide, with 86% of participants in this group achieving a normal liver fat percentage by the end of the study⁶.

One of the studies more carefully looked at changes in body composition while on retatrutide, as there has been some concern about lean mass loss while taking these types of drugs. Body composition was analysed by DXA scan and found that retatrutide produced reductions in lean mass similar to what has been observed from other weight loss drugs⁷.

The Latest Retatrutide Study

Eli Lilly recently released the results of their latest Phase 3 obesity trial⁸, demonstrating retatrutide’s ability to repeatedly produce profound weight loss results. The participants of this study were all obese adults without diabetes, but with at least one weight-related comorbidity.

Weight Reduction

Retatrutide produced a dose-dependent reduction in weight over the 80 week trial period, with participants taking 4, 9 and 12 mg losing an average of 47.2, 64.4 and 70.3 lbs, respectively. In terms of total body weight percentage lost, this equated to a 19 – 28.3% reduction. This reduction in weight led to 65.3% of participants transitioning from being obese to a healthier weight with a BMI of less than 30.

Participants with a BMI greater than 35 who took 12 mg of retatrutide for a longer period of 104 weeks, lost an average of 30.3% (85lbs) of their body weight

Cardiovascular Risk Factors

Waist circumference was also measured, and participants taking 12 mg reduced their waist measurements by an average of 24.1 cm after 80 weeks of treatment, suggesting the loss of visceral fat.

Blood parameters, including non-HDL cholesterol, triglycerides, systolic blood pressure and hsCRP, significantly improved in participants over the course of the study, indicating that cardiovascular risk could be reduced.

Diabetes

In the Phase 3 trial that looked at retatrutide’s effect in people with type 2 diabetes, participants received retatrutide for 40 weeks and HbA_1C and body weight were measured. A dose-dependent reduction in HbA_1C was observed. Participants taking 4, 9 and 12 mg of retatrutide experienced a 1.69, 1.86 and 1.94 reduction in HbA_1C, respectively.

Body weight was also reduced by an average of 11.5, 13.9 and 15.3% in the groups taking 4, 9 and 12 mg, respectively⁹.

Adverse Events and Discontinuation

The adverse events reported were those typical of other incretin-based therapies, including:

Nausea
Diarrhoea
Constipation
Vomiting
Upper respiratory tract infection

Dysesthesia was also reported by 12.5% of patients given the 12 mg dose and participants in all groups experienced an increase in incidence of urinary tract infections.

Discontinuation of the treatment due to adverse events was more likely in the groups receiving higher doses, with 11.3% of participants receiving 12 mg retatrutide dropping out of the study. Only 4.1% of participants taking the 4 mg dose discontinued treatment.

Other Uses Explored

Retatrutide is also being studied for its ability to treat knee osteoarthritis pain and moderate to severe sleep apnoea, the results of which are expected to be released later.

What We Don’t Know

When weight is lost rapidly, lean mass is often lost in conjunction with fat mass. These reports make no mention of body composition and only report the change in overall body weight. A minimal loss of lean mass is ideal, especially muscle tissue, as this helps to prevent frailty and is metabolically active.

Although this 80-104 week study is the longest study yet on retatrutide, there may be side effects that we have yet to discover. People tend to be averse to discontinuing these types of treatments and thus are likely to take them for several years. Only through continued monitoring will we learn more about the long-term implications of taking retatrutide.

Further monitoring of these patients after they have discontinued treatment will provide valuable insight into how likely it is that patients will be able to maintain weight loss results after reaching their weight and health goals. Much of the research on incretin-based therapies so far would suggest that a large percentage of people are likely to regain weight upon cessation of the medication¹⁰.

The Future of Retatrutide

Since the Phase 3 trials are ongoing, and although results are looking promising, we still do not know if or when it will receive approval.

Conclusion

Retatrutide is a novel, triple receptor agonist that targets not only GLP-1R but also GIPR and GCGR to elicit powerful weight loss effects that confer cardiovascular health benefits. Trials have consistently demonstrated this drug’s potent ability to reduce body weight, improve blood markers for cardiovascular risk and reduce visceral fat. The adverse events associated with retatrutide are similar to those reported from the use of other GLP-1RAs and, in some cases, are severe enough that participants choose to discontinue treatment. We are currently awaiting the results of the remaining Phase 3 trials, after which we will see if approval for this drug can be sought.

References

Gutgesell RM, Khalil A, Liskiewicz A, et al. GIPR agonism and antagonism decrease body weight and food intake via different mechanisms in male mice. Nat Metab. 2025;7(6):1282-1298. doi:10.1038/s42255-025-01294-x
Al-Massadi O, Fernø J, Diéguez C, Nogueiras R, Quiñones M. Glucagon Control on Food Intake and Energy Balance. Int J Mol Sci. 2019;20(16):3905. doi:10.3390/ijms20163905
Kanu C, Boye KS, Poon JL, et al. Appetite, eating attitudes, and eating behaviours during treatment with retatrutide in adults with type 2 diabetes: Results of a phase 2 study. Diabetes Obes Metab. 2025;27(12):6988-6998. doi:10.1111/dom.70097
Jastreboff AM, Kaplan LM, Frías JP, et al. Triple-Hormone-Receptor Agonist Retatrutide for Obesity – A Phase 2 Trial. N Engl J Med. 2023;389(6):514-526. doi:10.1056/NEJMoa2301972
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
Lilly’s triple agonist, retatrutide, delivered powerful weight loss in pivotal Phase 3 obesity trial.
Bajaj HS, Welch M, Shah P, et al. Efficacy and safety of retatrutide, a GIP, GLP-1, and glucagon receptor agonist, in people with type 2 diabetes and inadequate glycaemic control with diet and exercise (TRANSCEND-T2D-1): a double-blind, randomised, phase 3 trial. Lancet. 2026;407(10546):2402-2413. doi:10.1016/S0140-6736(26)00967-0
Quarenghi M, Capelli S, Galligani G, Giana A, Preatoni G, Turri Quarenghi R. Weight Regain After Liraglutide, Semaglutide or Tirzepatide Interruption: A Narrative Review of Randomized Studies. J Clin Med. 2025;14(11):3791. doi:10.3390/jcm14113791

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.