Mazdutide Explained: What Human Trials Show

Mazdutide is one of the newer metabolic peptides being studied for obesity and type 2 diabetes. It is often grouped with semaglutide, tirzepatide and retatrutide, but its receptor profile is different. Mazdutide activates the GLP-1 receptor and the glucagon receptor, giving it a two receptor mechanism that has now been tested in several randomised human trials.

The main question is no longer whether mazdutide can change body weight or glucose measures in people. It can. The more useful questions are how large those effects were in controlled trials, how consistent they were across different populations, what adverse events were seen, and how much uncertainty remains when the results are compared with other incretin medicines.

What is mazdutide?

Mazdutide, previously known as IBI362 or LY3305677, is a peptide designed to activate both the GLP-1 receptor and the glucagon receptor Mechanistic ¹.

The dual receptor design is the reason mazdutide is classed differently from GIP and GLP-1 dual agonists such as tirzepatide. Receptor activity alone should not be treated as proof of clinical benefit. The useful evidence comes from randomised human trials.

What did the first obesity phase 2 trial show?

One of the key earlier studies was a randomised, double blind, placebo controlled phase 2 trial in 248 Chinese adults with overweight or obesity. Participants were assigned to mazdutide or placebo for 24 weeks Human ².

Mean body weight change at week 24 was:

6.7% lower with the 3 mg mazdutide group;
10.4% lower with the 4.5 mg group;
11.3% lower with the 6 mg group; and
1.0% higher with placebo.

The treatment difference versus placebo ranged from 7.7 to 12.3 percentage points, with all mazdutide comparisons statistically significant.

This was an important signal, but it was still a phase 2 trial. Larger phase 3 studies were needed to test whether the effect held up in a broader late stage programme.

What did GLORY-1 show in phase 3?

GLORY-1 was a phase 3, double blind, placebo controlled obesity trial in China. It randomised 610 adults with obesity, or overweight plus at least one weight related condition, to mazdutide or placebo for 48 weeks Human ³.

At week 32, mean body weight change from baseline was:

10.09% lower with 4 mg mazdutide;
12.55% lower with 6 mg mazdutide; and
0.45% higher with placebo.

A reduction of at least 5% of baseline body weight was reached by 73.9% of the 4 mg group, 82.0% of the 6 mg group and 10.5% of the placebo group.

Those results established that the weight effect seen in phase 2 was reproducible in a larger phase 3 population.

What did the higher dose GLORY-2 trial find?

A second phase 3 study, GLORY-2, tested mazdutide in Chinese adults with obesity, defined in that trial as a body mass index of at least 30. The study included participants with or without type 2 diabetes and compared mazdutide with placebo over 60 weeks Human ⁴.

Among 461 treated participants, mean body weight change at week 60 was 16.65% lower with mazdutide and 1.50% lower with placebo. The between group difference was 15.15 percentage points.

At least 5% weight reduction was achieved by 84.3% of participants receiving mazdutide and 33.1% receiving placebo.

GLORY-2 matters because it extends the obesity evidence beyond the shorter phase 2 programme and shows that sizeable weight reduction was maintained through a longer controlled study. It should still be interpreted in the population that was actually studied rather than treated as a universal estimate for every patient group.

What does the new US phase 2 trial add?

The newest major obesity paper is a US based phase 2 trial published in August 2026. It enrolled 179 adults with obesity or overweight without type 2 diabetes across 24 centres in the United States Human ¹.

At week 32, least squares mean body weight change was:

7.3% lower in the 3 to 6 mg group;
15.6% lower in the 10 mg group;
18.1% lower in the 16 mg group; and
0.9% lower with placebo.

The trial also reported further body weight reduction by week 48.

This study is useful because most of the larger late stage mazdutide evidence had previously come from China. A US trial does not remove every question about generalisability, but it shows that the obesity signal was not confined to one national study programme.

The highest dose group also had the highest rate of treatment discontinuation because of adverse events, at 20%, mainly linked to gastrointestinal disorders. That is an important counterweight to the larger weight reduction seen in that group.

What has mazdutide shown in type 2 diabetes?

Mazdutide has also been tested in large phase 3 diabetes trials.

In one placebo controlled phase 3 study, 320 Chinese adults with type 2 diabetes that was inadequately controlled with diet and exercise were randomised to mazdutide or placebo. At week 24, HbA1c changed by 1.57 percentage points lower with 4 mg mazdutide, 2.15 points lower with 6 mg mazdutide and 0.14 points lower with placebo Human ⁵.

Body weight changed by 5.61% lower, 7.81% lower and 1.26% lower, respectively.

A separate phase 3 trial compared mazdutide with dulaglutide in 731 Chinese adults with type 2 diabetes who were also receiving background oral diabetes medicines. At week 28, both mazdutide groups met the trial criteria for noninferiority and superiority to dulaglutide for HbA1c reduction. Mazdutide also produced greater body weight reductions than dulaglutide Human ⁶.

These diabetes trials show that mazdutide is being studied as more than an obesity drug. They also make it important to keep weight loss and glucose control as separate clinical outcomes rather than treating one as proof of the other.

What adverse events have been reported?

Across the human trials, gastrointestinal adverse events are the most consistent tolerability issue.

In GLORY-2, vomiting was reported in 53.1% of participants receiving mazdutide compared with 1.3% with placebo, nausea in 46.9% versus 3.2%, and diarrhoea in 39.4% versus 6.5%. Most adverse events were described as mild to moderate. Treatment discontinuation because of adverse events occurred in 2.9% of the mazdutide group and none of the placebo group Human ⁴.

The US phase 2 trial also found gastrointestinal events to be the most common adverse events, and discontinuation was most frequent in the highest dose group Human ¹.

That pattern is broadly familiar in incretin based obesity research, but each medicine has to be judged on its own trial data. Similar side effect categories do not mean identical safety profiles.

How does mazdutide differ from tirzepatide and retatrutide?

The receptor combinations are different.

Mazdutide targets GLP-1 and glucagon receptors. Tirzepatide targets GIP and GLP-1 receptors. Retatrutide targets GIP, GLP-1 and glucagon receptors.

That makes receptor biology an interesting comparison, but it does not create a valid ranking of clinical effectiveness. The mazdutide obesity trials used different populations, durations, comparators and statistical methods from the major tirzepatide and retatrutide studies.

There is no large phase 3 head to head trial establishing that mazdutide is better or worse than those medicines for obesity. Cross trial percentage comparisons can be useful for generating questions, but they are not a substitute for a direct randomised comparison.

For the wider incretin field, see the BioRx comparison of semaglutide, tirzepatide and retatrutide.

What are the main limitations of the evidence?

The mazdutide evidence base is now substantial enough to move beyond early speculation, but several limits remain.

First, much of the phase 3 evidence comes from Chinese populations. The new US phase 2 study adds geographic diversity, but it is smaller than the Chinese phase 3 programme.

Second, most obesity trials have focused on body weight and metabolic risk markers. Weight reduction is clinically relevant, but it is not the same outcome as fewer heart attacks, strokes, kidney events or deaths.

Third, different trials used different doses, durations and analysis approaches. A single headline percentage cannot summarise the whole programme.

Fourth, key trials were industry funded. GLORY-1 was funded by Innovent Biologics and the US phase 2 trial was funded by Eli Lilly ³ ¹. Funding does not invalidate a randomised trial, but study design, prespecified endpoints and complete safety reporting remain important when the evidence is interpreted.

What is the UK position?

The MHRA's current public guidance describes several GLP-1 medicines that are licensed in the UK, including semaglutide, tirzepatide and liraglutide ⁷. Mazdutide is not named in that guidance table.

That table should not be treated as an exhaustive marketing authorisation search. The MHRA directs users to its product information service for medicine specific authorisation information ⁸. BioRx therefore does not infer UK approval from positive mazdutide trial results.

The distinction matters. Clinical trial success and regulatory authorisation are separate questions.

What does the evidence support today?

The strongest current conclusion is that mazdutide has produced meaningful weight reduction in several randomised human obesity trials and clinically important HbA1c reductions in randomised type 2 diabetes trials.

GLORY-1 and GLORY-2 provide late stage obesity evidence from China. The phase 3 diabetes programme shows effects on both glucose control and body weight. The 2026 US phase 2 trial adds evidence in a different population and found a clear dose response for weight reduction, while also showing more discontinuation at the highest tested dose.

What the evidence does not yet justify is treating mazdutide as interchangeable with semaglutide, tirzepatide or retatrutide, assuming that the largest cross trial weight loss number applies to every population, or describing it as an established UK medicine without a confirmed UK marketing authorisation.

For a broader explanation of the category, see peptides for weight loss and the BioRx guide to what peptides are.

Frequently asked questions

Is mazdutide a GLP-1 medicine?

Mazdutide activates the GLP-1 receptor, but it also activates the glucagon receptor. It is therefore described as a GLP-1 and glucagon dual agonist rather than a GLP-1 only drug Mechanistic.

Has mazdutide reached phase 3 trials?

Yes. Published phase 3 trials include obesity studies such as GLORY-1 and GLORY-2 and type 2 diabetes studies comparing mazdutide with placebo or dulaglutide Human.

How much weight loss has been reported?

The answer depends on the trial, population, duration and treatment group. In GLORY-1, mean body weight change at week 32 was 10.09% lower with 4 mg and 12.55% lower with 6 mg mazdutide, compared with a 0.45% increase with placebo. In GLORY-2, mean change at week 60 was 16.65% lower with mazdutide and 1.50% lower with placebo Human.

Has mazdutide been tested in the United States?

Yes. A US based phase 2 obesity trial published in August 2026 randomised 179 adults across 24 centres and reported statistically significant weight reduction across the tested mazdutide groups compared with placebo Human.

Is mazdutide proven to be better than tirzepatide or retatrutide?

No. The major results come from separate trial programmes. Without a suitable direct randomised comparison, cross trial weight loss percentages cannot establish which treatment is better.

Is mazdutide an approved medicine in the UK?

The current MHRA guidance reviewed for this article names licensed UK GLP-1 medicines including semaglutide, tirzepatide and liraglutide, but does not name mazdutide in its table. Current medicine specific authorisation information should be checked through the MHRA product information service rather than inferred from trial results.

References

Studies marked "View study in BioRx" sit in the clinical studies index with their design and evidence grade.

Mazdutide Explained: What Human Trials Show in 2026