Mazdutide Clinical Data: Weight Loss in Asian Populations

Mazdutide

20.1% weight loss

In the GLORY-2 trial, mazdutide 9 mg produced 20.1% mean weight loss at 60 weeks in Chinese adults with obesity who did not have type 2 diabetes.

Innovent Biologics, GLORY-2 Phase 3, 2025

Innovent Biologics, GLORY-2 Phase 3, 2025

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Mazdutide (IBI362) is a once-weekly GLP-1 and glucagon receptor dual agonist developed by Innovent Biologics in China. Unlike tirzepatide, which targets GLP-1 and GIP receptors, mazdutide pairs GLP-1 with glucagon receptor activation, a combination designed to enhance both appetite suppression and energy expenditure. Every completed clinical trial of mazdutide has enrolled Chinese adults exclusively, making it the most extensively studied incretin-based weight loss drug in an Asian population. The GLORY-1 phase 3 trial, published in the New England Journal of Medicine in 2025, showed the 6 mg dose produced 14.01% mean weight loss at 48 weeks in 610 Chinese adults with overweight or obesity.^[1] The subsequent GLORY-2 trial pushed that further: 9 mg produced 20.1% weight loss at 60 weeks.

The Clinical Trial Timeline

Mazdutide's clinical evidence has built systematically from small dose-finding studies to large phase 3 trials, all conducted in Chinese adults.

Phase 1b: Dose Exploration (2022)

The earliest high-dose data came from a phase 1b trial enrolling 24 Chinese adults with overweight or obesity. Participants receiving mazdutide 9 mg lost a mean of 11.7% of body weight over just 12 weeks, compared to 1.8% with placebo. The 10 mg cohort lost 9.5% over 16 weeks. No serious adverse events were reported, and all treatment-emergent events were mild or moderate.^[2] The sample was small (8 active per cohort), but the speed of weight loss at 9 mg prompted the larger trials that followed.

Phase 2: Establishing the Dose-Response Curve (2023-2024)

Two phase 2 trials defined mazdutide's dose-response relationship, one in obesity and one in type 2 diabetes.

In the obesity trial, 248 Chinese adults were randomized to mazdutide 3 mg, 4.5 mg, 6 mg, or placebo for 24 weeks. Weight loss was dose-dependent: 6.7% at 3 mg, 10.4% at 4.5 mg, and 11.3% at 6 mg, versus 1.0% weight gain with placebo. Treatment differences ranged from 7.7% to 12.3% versus placebo (all P < 0.0001). The most common side effects were diarrhea, nausea, and upper respiratory tract infection.^[3]

In the type 2 diabetes trial, 250 Chinese adults received mazdutide (3, 4.5, or 6 mg), open-label dulaglutide 1.5 mg, or placebo for 20 weeks. Mazdutide 6 mg reduced HbA1c by 1.67% (versus +0.03% placebo) and body weight by 7.1% (versus -2.7% with dulaglutide and -1.4% with placebo). This trial was the first signal that mazdutide's glucagon co-activation produces meaningfully greater weight loss than a pure GLP-1 agonist at comparable dose timelines.^[4]

Phase 3: GLORY and DREAMS Programs

GLORY-1: The NEJM Landmark (2025)

The pivotal GLORY-1 trial randomized 610 Chinese adults (BMI 28 or higher, or BMI 24-28 with comorbidities) in a 1:1:1 ratio to mazdutide 4 mg, mazdutide 6 mg, or placebo for 48 weeks. This trial was published in the New England Journal of Medicine.^[1]

At the primary endpoint of 32 weeks:

• Mean weight loss was 10.09% (4 mg), 12.55% (6 mg), and +0.45% (placebo)
• 73.9% (4 mg) and 82.0% (6 mg) of participants achieved at least 5% weight loss, versus 10.5% with placebo

At 48 weeks (extended follow-up):

• Mean weight loss was 11.00% (4 mg) and 14.01% (6 mg), versus +0.30% (placebo)
• 35.7% (4 mg) and 49.5% (6 mg) achieved at least 15% weight loss, versus 2.0% with placebo
• Beneficial effects were observed across all prespecified cardiometabolic measures

The discontinuation rate due to adverse events was remarkably low: 1.5% with 4 mg, 0.5% with 6 mg, and 1.0% with placebo. Gastrointestinal events were the most common side effects and mostly mild to moderate.

GLORY-2: The 9 mg Dose (2025)

GLORY-2 tested the higher 9 mg dose in 462 Chinese adults with obesity (BMI 30 or higher, including 16% with type 2 diabetes) for 60 weeks. Results were reported as press releases:

• Mean weight loss at 60 weeks: 18.55% overall, and 20.08% in participants without type 2 diabetes
• 48.7% of non-diabetic participants achieved at least 20% weight loss (versus 3.1% with placebo)
• The trial met its primary endpoint and all key secondary endpoints

The 20% weight loss threshold is notable because it approaches the territory previously occupied only by tirzepatide at its highest doses and longer treatment durations. The BMI threshold of 28 used in Chinese trials is lower than the 30 used in Western trials, reflecting different obesity classification standards in Asian populations. This matters for interpreting the data: Chinese participants in GLORY trials started at lower absolute body weights than participants in Western GLP-1 trials, and percentage weight loss from a lower baseline represents a different physiological context.

DREAMS-3: Head-to-Head Against Semaglutide (2025)

The DREAMS-3 trial provided the first direct comparison between mazdutide and semaglutide. In 349 Chinese adults with early-stage type 2 diabetes and obesity:

• 48.0% of the mazdutide group achieved both HbA1c below 7% and at least 10% weight loss at 32 weeks, versus 21.0% in the semaglutide group
• Mean weight loss was 10.29% with mazdutide versus 6.00% with semaglutide

This trial positioned mazdutide as superior to semaglutide on the composite endpoint of glycemic control plus weight loss. The glucagon receptor component may explain the weight loss advantage: glucagon activation increases hepatic glucose output in the short term but also increases energy expenditure, lipolysis, and thermogenesis.

Mazdutide vs. Dulaglutide: A Nature-Published Phase 3

A separate phase 3 trial published in Nature randomized 731 Chinese adults with type 2 diabetes to mazdutide 4 mg, mazdutide 6 mg, or dulaglutide 1.5 mg for 28 weeks. Both mazdutide doses demonstrated non-inferiority and superiority to dulaglutide for HbA1c reduction. The least-squares mean treatment difference was -0.24% for mazdutide 4 mg and -0.30% for mazdutide 6 mg relative to dulaglutide. Weight loss differences were even more pronounced: -3.78% (4 mg) and -5.76% (6 mg) greater than dulaglutide.^[5]

Gastrointestinal adverse events were more frequent with mazdutide than dulaglutide, consistent with the dual-agonist mechanism producing stronger appetite and gut motility effects.

How Mazdutide Compares in Meta-Analyses

Two independent meta-analyses have positioned mazdutide within the broader landscape of incretin-based drugs.

A network meta-analysis by Liu and colleagues, pooling 24 trials with 9,165 participants, found that mazdutide produced HbA1c reductions of 1.89% (P < 0.0001 vs. placebo), ranking among the most effective agents alongside tirzepatide (1.87%) for glycemic control. For weight loss, tirzepatide and retatrutide ranked highest, though mazdutide trials used shorter durations and lower maximum doses at the time of the analysis.^[6]

A separate meta-analysis by Chan and colleagues of 10 randomized controlled trials (3,236 participants) evaluating dual and triple agonists found a pooled weight reduction of 11.47 kg versus placebo (95% CI: 8.95-14.00) across agents including tirzepatide, retatrutide, and mazdutide. The analysis confirmed that multi-receptor agonists produced greater weight loss than single-receptor GLP-1 drugs, but with higher rates of gastrointestinal adverse events (nausea, vomiting, diarrhea) and a 3-fold increase in hypoglycemic episodes.^[7]

The Asian Population Question

All completed mazdutide clinical trials enrolled Chinese adults exclusively. This is unusual for a major metabolic drug. How mazdutide compares to Western-developed metabolic peptides is a question that cannot be answered with cross-trial comparisons alone because of population differences.

Three factors make direct comparisons with Western GLP-1 trial data difficult:

Different BMI thresholds. Chinese obesity trials use a BMI cutoff of 28, while Western trials use 30. The WHO recognizes that Asian populations develop metabolic complications at lower BMI values, so these thresholds reflect real clinical differences, not arbitrary standards. Participants in GLORY-1 had a mean BMI of 31.1, compared to 37.9 in the STEP trials (semaglutide) and 38.0 in SURMOUNT (tirzepatide). Starting from a lower body weight means the same percentage weight loss represents fewer absolute kilograms.

Metabolic phenotype differences. Asian populations tend to accumulate more visceral fat at lower BMI values and develop insulin resistance earlier. This may make them more responsive to glucagon receptor activation, which preferentially targets visceral fat stores and hepatic lipid metabolism. Whether mazdutide's glucagon component provides a particular advantage in Asian metabolic profiles is an open question.

Trial duration differences. GLORY-1 assessed the primary endpoint at 32 weeks (48 weeks extended), while the pivotal semaglutide and tirzepatide obesity trials ran to 68-72 weeks. Longer treatment duration generally produces greater weight loss. The GLORY-2 trial at 60 weeks with 9 mg partially addresses this gap.

A phase 1b trial of mazdutide in Chinese adolescents with obesity reported positive results in late 2025, suggesting the drug may extend to younger populations. No non-Asian population data has been published.

Safety Profile Across Trials

The safety signal across all mazdutide trials is consistent: gastrointestinal side effects dominate, and serious adverse events are rare.

In the phase 2 T2D trial, the most common adverse events with mazdutide were diarrhea (36%), decreased appetite (29%), nausea (23%), vomiting (14%), and hypoglycemia (10%, versus 8% with placebo).^[4]

In GLORY-1, the discontinuation rate due to adverse events was below 2% across all groups, including placebo, suggesting that the gastrointestinal effects are tolerable for the vast majority of patients.^[1]

In the mazdutide vs. dulaglutide trial, GI adverse events were more common with mazdutide, but no new safety signals emerged beyond what has been observed with other GLP-1 receptor agonists.^[5]

The glucagon receptor component raises theoretical concerns about hepatic glucose output increasing blood sugar in diabetic patients. In practice, the GLP-1 component appears to counterbalance this effect: HbA1c reductions with mazdutide consistently exceeded those of GLP-1-only drugs at comparable timepoints.

Preclinical work has also explored mazdutide beyond metabolic endpoints. Dong and colleagues demonstrated in a mouse model that mazdutide improved cognitive performance in diabetic mice compared to dulaglutide, through mechanisms involving neuroprotection, energy metabolism, and synaptic plasticity.^[8] These findings are animal-only and cannot be extrapolated to human cognitive outcomes.

What the Data Does Not Answer

Several questions remain unresolved:

Weight regain after discontinuation. No published mazdutide trial has reported what happens to weight after the drug is stopped. Every other GLP-1 class drug shows substantial weight regain after discontinuation, and there is no reason to assume mazdutide will differ.

Long-term safety beyond 60 weeks. The longest published trial ran 60 weeks. Cardiovascular outcome data, cancer risk assessments, and pancreatic safety evaluations over multiple years do not exist yet.

Efficacy in non-Asian populations. Without trials in diverse populations, it remains unknown whether the weight loss percentages observed in Chinese adults will translate to Western populations with different metabolic profiles and higher starting BMIs.

Comparison with tirzepatide. No head-to-head trial has compared mazdutide (GLP-1/glucagon) against tirzepatide (GLP-1/GIP). Cross-trial comparisons suggest comparable efficacy at their respective highest doses, but only a direct randomized comparison can confirm this.

The Bottom Line

Mazdutide has produced some of the strongest weight loss data in any Asian clinical trial population. The GLORY program demonstrated 14-20% weight loss depending on dose and duration, the DREAMS-3 trial showed superiority over semaglutide on a composite metabolic endpoint, and the Nature-published trial confirmed superiority over dulaglutide. The safety profile is consistent with the GLP-1 drug class. The major limitation is that all data comes from Chinese adults, making cross-population generalizability an open question. No long-term data beyond 60 weeks and no cardiovascular outcomes data exist yet.

Frequently Asked Questions

How much weight can you lose on mazdutide?

In the GLORY-1 phase 3 trial, mazdutide 6 mg produced 14.01% mean weight loss at 48 weeks in 610 Chinese adults. The GLORY-2 trial showed the higher 9 mg dose achieved 20.1% weight loss at 60 weeks in non-diabetic participants. Nearly half (49.5%) of participants on the 6 mg dose lost at least 15% of body weight by 48 weeks.

Is mazdutide better than semaglutide for weight loss?

In the DREAMS-3 head-to-head trial, mazdutide produced 10.29% weight loss versus 6.00% for semaglutide at 32 weeks in Chinese adults with type 2 diabetes and obesity. On the composite endpoint of HbA1c below 7% plus at least 10% weight loss, 48% of the mazdutide group succeeded versus 21% with semaglutide. Cross-trial comparisons with higher-dose semaglutide (2.4 mg Wegovy) are unreliable due to different populations and trial designs.

What are the side effects of mazdutide?

Gastrointestinal effects are the most common: diarrhea (36%), decreased appetite (29%), nausea (23%), and vomiting (14%) in the phase 2 diabetes trial. These were mostly mild to moderate. In the GLORY-1 phase 3 trial, fewer than 2% of participants discontinued due to adverse events, which was comparable to the placebo group's discontinuation rate.

How is mazdutide different from tirzepatide?

Both are dual-receptor agonist peptides, but they target different receptor pairs. Tirzepatide activates GLP-1 and GIP receptors, while mazdutide activates GLP-1 and glucagon receptors. Glucagon activation may increase energy expenditure and fat oxidation more than GIP activation. No head-to-head trial has compared them directly.

Is mazdutide available in the United States?

Mazdutide received regulatory approval in China in 2025 for obesity treatment. It is not available in the United States, Europe, or other markets. All published clinical trial data comes from Chinese adults. Innovent Biologics has not announced US or European regulatory filings as of early 2026.

Does mazdutide work for type 2 diabetes?

Yes. In a phase 3 trial published in Nature, mazdutide 6 mg reduced HbA1c by 0.30% more than dulaglutide 1.5 mg over 28 weeks in 731 Chinese adults with type 2 diabetes. A network meta-analysis of 9,165 participants ranked mazdutide among the most effective incretin drugs for glycemic control, with an HbA1c reduction of 1.89%.