In June of 2025, Mazdutide was approved for the use of weight management and type 2 diabetes (T2D) in China, under the name of Xinermei. This drug was developed by Eli Lilly, a company also responsible for the development of tirzepatide (sold as Mounjaro® and Zepbound®) and dulaglutide (sold as Trulicity®), both of which are very effective weight loss drugs. Mazdutide has demonstrated some impressive results in clinical trials, so in this article, we will find out how it works and how it compares to other similar weight loss drugs.

What Kind of Drug Is Mazdutide?

GLP-1RAs (Glucagon-Like Peptide-1 Receptor Agonists) are a class of weight loss drugs that work by stimulating GLP-1 receptors. However, GLP-1RAs do not necessarily target this one receptor alone. Drugs with multiple receptor targets have been developed, which synergistically promote weight loss.

Mazdutide is a dual agonist, meaning that it activates the receptors of two different hormones, GLP-1 and glucagon (GCG). It is the first weight loss peptide to target this combination of receptors. The activation of these dual receptors by mazdutide is intended to promote even greater weight loss than what just one receptor alone could achieve.

So, why have these receptors been chosen as targets for this new drug? We can answer this question by first looking at when these receptors are normally activated and how the body responds to this.

The Result of GLP-1 Receptor Agonism

GLP-1R is activated by GLP-1, a hormone produced naturally by the body. The production of GLP-1 is normally stimulated in response to eating a meal, promoting satiety, slowing digestion, and regulating the release of insulin to maintain blood glucose levels. The importance of this becomes even clearer when we look at examples where GLP-1 secretion is lower than normal or where the receptor has a dulled response to GLP-1¹.

If blood glucose levels are chronically elevated, as they are in cases of unmanaged diabetes, β-cells of the pancreas will reduce the expression of GLP-1 receptors, and the existing receptors will have impaired signalling. This results in less insulin being secreted in response to glucose, meaning that when blood glucose levels rise in response to a meal, they remain high for much longer than normal². This increases the risk of developing sepsis, damage to organs and tissues, and promotes cancer progression³.

The Results of GCG Receptor Agonism

GCG receptors are activated by GCG, a hormone that is typically secreted in response to fasting or low blood sugar levels. It promotes the expenditure of energy and the burning of fat. When blood glucose levels are high, GCG release is suppressed.

GCG is essential for stimulating the release of insulin, so without sufficient GCG, the body is less able to regulate glucose levels. Hypoglycaemia is also more likely, as GCG helps to raise blood sugar levels when they are too low⁴.

The Combined Effect of GLP-1 and GCG Receptor Agonism

Now that we know what hormones bind to these receptors and what that entails, we can appreciate that these receptors were chosen as drug targets with the intention that they should:

Reduce hunger, which reduces food cravings and lowers calorie intake, promoting weight loss.
Increase sensitivity to insulin to help control blood sugar levels.
Increase the burning of fat calories to promote weight loss.
Increase the release of glucose when blood sugar levels drop, preventing hypoglycaemia and regulating blood sugar levels.

Comparing Results With Other GLP-1R Agonists

There are several different GLP-1RAs available on the market. The doses they are administered in, the receptors they target, what they are approved for treating, and the severity of the side effects they may cause all vary.

When it comes to comparing them directly, this is difficult since there is limited overlap between the doses and periods of time over which they were tested. Conveniently, a meta-analysis was conducted comparing several GLP-1RAs⁵.

We will go over the results of the most popular single-target receptor agonist, semaglutide, a dual receptor agonist, tirzepatide, and a triple receptor agonist, retatrutide, comparing them with mazdutide’s results.

Mazdutide vs Semaglutide

Semaglutide (Ozempic®) is a GLP-1RA that targets only the GLP-1 receptor. At a dose of 2.4 mg/week, it produces slightly better weight loss results (-11.53%) than 4.5 mg of mazdutide (11.08%) in non diabetics, but may be a significantly better choice of weight loss drug for those who have T2D. Mazdutide caused a 3.92% reduction in weight in those with T2D, compared to 6.22% for semaglutide.

Mazdutide vs Tirzepatide

Tirzepatide is a dual receptor agonist, targeting GLP-1 and GIP receptors. 10 mg/week of tirzepatide reduced weight by 13.92% while 6 mg/week of Mazdutide caused a loss of 12.73% in body weight. In people with T2D, tirzepatide reduced weight by 8.92%, compared to 5.73% with mazdutide.

Mazdutide vs Retatrutide

Retatrutide is an experimental, triple receptor agonist that targets GLP-1, GIP and GCG receptors. 8 mg/week of retatrutide produced a 20.7% reduction in weight, outperforming all other drugs. In those with T2D, it produced a 13.08% reduction in weight, again, producing the most significant weight loss compared to the other GLP-1RAs.

Since different doses were tested, comparing these values directly would not be fair. We do know that the efficacy of these drugs tends to increase as the dose increases, but may taper off instead of continuing to improve linearly.

Mazdutide in More Detail

Based on the results from clinical trials, mazdutide has delivered strong results that demonstrate its efficacy as a drug for lowering weight and managing T2D.

If we compare more than just weight loss, we find that Mazdutide stands out in its ability to improve:

HbA1c: In one study, mazdutide improved HbA1c by 2.02%⁶.
Lipid profiles: It reduced the accumulation of fat in the liver and hepatic fibrosis to a greater extent than a single target GLP-1 or GCG receptor agonist⁷.

Side Effects

The use of GLP-1RAs is most commonly associated with the following side effects:

Nausea
Vomiting
Diarrhoea
Constipation
Abdominal pain

These side effects are most severe at higher doses or during the process of increasing doses (titration). The severity decreases over time as the body adapts to the drug^8,9.

Less common but more severe side effects can include:

Pancreatitis
Gallbladder disease¹⁰

Most people experience side effects that are mild to moderate in severity, so GLP-1RAs, have a favourable safety profile. Since mazdutide is still relatively new, we may learn more about its side effects in time, but the clinical trials have reported reassuringly predictable adverse events so far.

Contraindications

Drugs that target these receptors are not recommended for all people due to some concerns that were raised by animal studies and from what we have learned from clinical research^11,12. It is not recommended for:

Those with a history of pancreatitis.
People with gallbladder disease.
People at risk of or with a family history of medullary thyroid cancer or multiple endocrine neoplasia type 2.
Those who are pregnant or trying to conceive.

Conclusion

Although mazdutide is not yet available in the UK, it has been tested on Chinese populations and has demonstrated some strong positive results. It has been approved as a drug for the treatment of obesity, T2D and fatty liver. It may not produce the strongest weight loss results when compared with other GLP-1RAs, but it still reduces weight significantly. In addition to this, it is exceptionally good at lowering HbA1c and is able to provide greater benefits to the liver than other GLP-1RAs. Overall, this drug appears to be effective at treating the conditions for which it has been approved.

Buy mazdutide here.

References

Müller TD, Finan B, Bloom SR, et al. Glucagon-like peptide 1 (GLP-1). Mol Metab. 2019;30:72-130. doi:10.1016/j.molmet.2019.09.010
Rajan S, Dickson LM, Mathew E, et al. Chronic hyperglycemia downregulates GLP-1 receptor signaling in pancreatic β-cells via protein kinase A. Mol Metab. 2015;4(4):265-276. doi:10.1016/j.molmet.2015.01.010
Giri B, Dey S, Das T, Sarkar M, Banerjee J, Dash SK. Chronic hyperglycemia mediated physiological alteration and metabolic distortion leads to organ dysfunction, infection, cancer progression and other pathophysiological consequences: An update on glucose toxicity. Biomed Pharmacother. 2018;107:306-328. doi:10.1016/j.biopha.2018.07.157
Winther JB, Holst JJ. Glucagon agonism in the treatment of metabolic diseases including type 2 diabetes mellitus and obesity. Diabetes Obes Metab. 2024;26(9):3501-3512. doi:10.1111/dom.15693
Xie Z, Zheng G, Liang Z, Li M, Deng W, Cao W. Seven glucagon-like peptide-1 receptor agonists and polyagonists for weight loss in patients with obesity or overweight: an updated systematic review and network meta-analysis of randomized controlled trials. Metab – Clin Exp. 2024;161. doi:10.1016/j.metabol.2024.156038
Zhu D, Zhao J, CAI H, et al. 306-OR: Mazdutide vs. Placebo as Monotherapy in Patients with Type 2 Diabetes (DREAMS-1). Diabetes. 2025;74(Supplement_1):306-OR. doi:10.2337/db25-306-OR
Wang H, Li L. 1616-P: Effect of Mazdutide on MASH Fibrosis—Targeting the Liver–Gut Axis and Microbiome. Diabetes. 2025;74(Supplement_1):1616-P. doi:10.2337/db25-1616-P
Nalisa DL, Cuboia N, Dyab E, et al. Efficacy and safety of Mazdutide on weight loss among diabetic and non-diabetic patients: a systematic review and meta-analysis of randomized controlled trials. Front Endocrinol. 2024;15:1309118. doi:10.3389/fendo.2024.1309118
Kommu S, Berg RL. Efficacy and safety of once-weekly subcutaneous semaglutide on weight loss in patients with overweight or obesity without diabetes mellitus—A systematic review and meta-analysis of randomized controlled trials. Obes Rev. 2024;25(9):e13792. doi:10.1111/obr.13792
Zeng Q, Xu J, Mu X, Shi Y, Fan H, Li S. Safety issues of tirzepatide (pancreatitis and gallbladder or biliary disease) in type 2 diabetes and obesity: a systematic review and meta-analysis. Front Endocrinol. 2023;14:1214334. doi:10.3389/fendo.2023.1214334
Bezin J, Gouverneur A, Pénichon M, et al. GLP-1 Receptor Agonists and the Risk of Thyroid Cancer. Diabetes Care. 2022;46(2):384-390. doi:10.2337/dc22-1148
Smits MM, Van Raalte DH. Safety of Semaglutide. Front Endocrinol. 2021;12. doi:10.3389/fendo.2021.645563

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.