Mazdutide vs Semaglutide and Tirzepatide Compared

Mazdutide

20.1% weight loss

In the GLORY-2 trial, mazdutide 9 mg produced 20.1% mean weight loss in Chinese adults without type 2 diabetes over 60 weeks.

Innovent Biologics, GLORY-2 Phase 3 Data, 2025

Innovent Biologics, GLORY-2 Phase 3 Data, 2025

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Three peptide-based drugs now dominate the metabolic medicine landscape, and each one activates a different combination of gut hormone receptors. Semaglutide (Wegovy/Ozempic) targets GLP-1 alone. Tirzepatide (Mounjaro/Zepbound) hits GLP-1 and GIP. Mazdutide (IBI362), developed by Innovent Biologics, targets GLP-1 and glucagon. That last combination had never been approved anywhere in the world until 2024, when China's NMPA cleared mazdutide for both weight management and type 2 diabetes. For background on mazdutide's development and mechanism, see our complete guide to mazdutide.

The question this article answers: how does mazdutide stack up against semaglutide and tirzepatide in clinical trials? The data comes from nine studies spanning Phase 1b through Phase 3, including the first head-to-head trial of a GLP-1/glucagon agonist against semaglutide.

What Makes Mazdutide Different: GLP-1 Plus Glucagon

Every comparison between these three drugs starts with their receptor targets. All three activate the GLP-1 receptor, which suppresses appetite, slows gastric emptying, and enhances insulin secretion. The difference is the second receptor.

Semaglutide activates GLP-1 only. It is a single-target agonist. The STEP 1 trial demonstrated 14.9% mean weight loss at 68 weeks with the 2.4 mg dose.^[7] This remains the benchmark for pure GLP-1 agonist therapy.

Tirzepatide activates both GLP-1 and GIP (glucose-dependent insulinotropic polypeptide). GIP's role is complex and not fully understood, but in combination with GLP-1 agonism, it appears to amplify insulin secretion and may have direct effects on adipose tissue. The SURMOUNT-1 trial showed up to 22.5% weight loss at the 15 mg dose over 72 weeks.^[6]

Mazdutide activates GLP-1 and the glucagon receptor (GCGR). Glucagon is traditionally associated with raising blood sugar, which makes its inclusion counterintuitive. But glucagon receptor activation also increases hepatic lipid oxidation (the liver burns more fat), raises resting energy expenditure, and promotes satiety through central nervous system pathways distinct from GLP-1.^[2] The theoretical advantage is that mazdutide attacks obesity from both the appetite side (GLP-1) and the energy expenditure side (glucagon) simultaneously.

This dual mechanism makes mazdutide particularly interesting for fatty liver disease. Glucagon receptor activation directly promotes hepatic fat clearance, a property that neither semaglutide nor tirzepatide possesses through their primary mechanisms.

Mazdutide vs Semaglutide: Head-to-Head Data

The DREAMS-3 trial was the first Phase 3 study to directly compare a GLP-1/glucagon dual agonist against semaglutide. Conducted in Chinese adults with type 2 diabetes and overweight or obesity, it randomized participants to mazdutide 6 mg or semaglutide 1 mg weekly for 32 weeks.

The primary endpoint was the proportion of participants achieving both HbA1c below 7% and at least 10% body weight loss. At 32 weeks, 48.0% of the mazdutide group met this combined endpoint, compared to 21.0% in the semaglutide group.^[4]

Breaking this down by individual outcomes: mazdutide produced a mean HbA1c reduction of 2.03% versus 1.84% for semaglutide, and a mean weight reduction of 10.29% versus 6.00%. Both the glycemic and weight outcomes favored mazdutide.

There are caveats. The semaglutide comparator dose was 1 mg (the diabetes dose), not 2.4 mg (the obesity dose). At 2.4 mg, semaglutide's weight loss performance would be substantially better. The trial was 32 weeks, shorter than the 68-week STEP trials. And the population was exclusively Chinese adults with T2D, a different metabolic profile than the non-diabetic Western populations in most semaglutide trials.

The GLORY-1 trial, published in the New England Journal of Medicine, tested mazdutide 4 mg and 6 mg against placebo in 610 Chinese adults with obesity or overweight. At week 48, the 6 mg group lost 14.01% of body weight versus 0.30% on placebo, with 49.5% achieving at least 15% weight loss.^[1] This 14% figure at 48 weeks is close to semaglutide 2.4 mg's 14.9% at 68 weeks in STEP 1, but at a lower dose and shorter timeframe.

Mazdutide vs Tirzepatide: Different Dual Targets

No head-to-head trial between mazdutide and tirzepatide has been completed, though one is planned. Current comparisons rely on cross-trial data, which is unreliable for definitive conclusions but useful for framing expectations.

The SURMOUNT-5 trial directly compared tirzepatide to semaglutide in adults with obesity but without diabetes. At 72 weeks, tirzepatide 15 mg produced 20.2% mean weight loss, compared to 13.7% for semaglutide 2.4 mg.^[5] This established tirzepatide as the current leader in single-agent weight loss among approved therapies.

Mazdutide's highest-dose data comes from the GLORY-2 trial, where the 9 mg dose achieved 20.1% mean weight loss at 60 weeks in non-diabetic Chinese adults, with 48.7% of participants losing 20% or more. These numbers are in the same range as tirzepatide's best results, though the shorter trial duration (60 vs 72 weeks), different population (Chinese vs primarily Western), and different BMI thresholds make direct comparison speculative.

The mechanistic question is whether GLP-1/glucagon (mazdutide's approach) or GLP-1/GIP (tirzepatide's approach) will ultimately prove more effective. Early data suggests they may converge on similar weight loss magnitudes but through different metabolic pathways. Mazdutide's glucagon component drives higher energy expenditure and more liver fat reduction. Tirzepatide's GIP component may enhance insulin sensitivity and adipose tissue function in ways that glucagon does not. Whether one advantage proves clinically superior will require head-to-head data.

Weight Loss Numbers Side by Side

Comparing weight loss across different trials is inherently imprecise. Trial populations differ in baseline BMI, ethnicity, diabetes status, and lifestyle interventions. Duration varies from 32 to 104 weeks. Doses are not equivalent across molecules. With those caveats, here are the headline numbers:

Semaglutide 2.4 mg (STEP 1): 14.9% mean weight loss at 68 weeks in non-diabetic adults with BMI 30+ (mean baseline BMI 37.9). 86.4% lost at least 5%.^[7]

Tirzepatide 15 mg (SURMOUNT-1): 22.5% mean weight loss at 72 weeks in non-diabetic adults with BMI 30+ (mean baseline BMI 38.0). 96% lost at least 5%.^[6]

Tirzepatide 15 mg vs semaglutide 2.4 mg (SURMOUNT-5): 20.2% vs 13.7% at 72 weeks, head-to-head, non-diabetic adults.^[5]

Mazdutide 6 mg (GLORY-1): 14.01% mean weight loss at 48 weeks in Chinese adults with BMI 28+ (mean baseline BMI 31.1). 82.0% lost at least 5%.^[1]

Mazdutide 9 mg (GLORY-2): 18.55% mean weight loss at 60 weeks in Chinese adults with obesity; 20.08% in those without T2D. 44.0% lost at least 20%.

Mazdutide 6 mg vs semaglutide 1 mg (DREAMS-3): 10.29% vs 6.00% at 32 weeks, head-to-head, T2D population.^[4]

The trend is clear: dual-receptor agonists (tirzepatide and mazdutide) produce greater weight loss than single-receptor semaglutide. Whether mazdutide can match tirzepatide's numbers when tested in similar populations and at optimal doses is the open question. For a broader comparison of the full GLP-1 agonist class, see our overview article.

Safety Profiles Across the Three Drugs

All three drugs share a common adverse event profile dominated by gastrointestinal symptoms: nausea, vomiting, diarrhea, and constipation. These effects are most prominent during dose escalation and tend to diminish over time.

In STEP 1, 44.2% of semaglutide users reported nausea (vs 17.4% placebo), and 4.5% discontinued due to GI events.^[7] In SURMOUNT-1, nausea affected 24.6% of tirzepatide users at the 15 mg dose.^[6] In GLORY-1, GI adverse events were the most common with mazdutide, but over 90% of participants completed treatment, suggesting tolerability was manageable.^[1]

Mazdutide's glucagon component raises a theoretical concern about blood sugar elevation, since glucagon's primary physiological role is raising glucose. In practice, the GLP-1 component appears to offset this effect. In the DREAMS-3 trial, mazdutide produced superior HbA1c reduction compared to semaglutide, indicating that the net glycemic effect is glucose-lowering, not glucose-raising.^[4]

Long-term safety data differs substantially. Semaglutide has over 8 years of clinical use and post-marketing surveillance across millions of patients globally. Tirzepatide has been in clinical use since 2022. Mazdutide was approved in China in 2024, giving it the shortest track record. Class-wide concerns like thyroid C-cell tumors (observed in rodent models), pancreatitis, and gallbladder disease apply to all three drugs, though the glucagon receptor adds a unique pharmacological variable to mazdutide that only extended use will fully characterize.

The Population Question: Asian vs Western Trial Data

The most significant limitation in comparing mazdutide to its competitors is population. Every Phase 3 mazdutide trial has enrolled exclusively Chinese participants. The STEP and SURMOUNT programs enrolled predominantly North American, European, and Latin American populations.

This matters because obesity phenotypes differ across ethnicities. Asian populations tend to develop metabolic complications at lower BMIs. The GLORY-1 trial used BMI thresholds of 28 (obesity) and 24 (overweight with comorbidity) for Chinese participants, compared to 30 and 27 in the STEP trials. Mean baseline BMI in GLORY-1 was 31.1, versus 37.9 in STEP 1. Participants starting at a higher baseline BMI typically lose more absolute weight, which inflates percentage-based comparisons.

Whether mazdutide's efficacy will replicate in Western populations with higher baseline BMIs and different metabolic profiles is unknown. The drug's GLP-1/glucagon mechanism should theoretically work regardless of ethnicity, but dose-response relationships, GI tolerability thresholds, and optimal titration schedules could all differ. Global trials outside China have not yet reported Phase 3 results.

For detailed data on mazdutide's performance specifically in Asian trial populations, see our article on mazdutide weight loss results in Asian populations.

Regulatory Status and Global Availability

As of early 2026, the regulatory landscape for these three drugs is asymmetric:

Semaglutide is approved for weight management (as Wegovy) and type 2 diabetes (as Ozempic) in the US, EU, UK, Japan, Australia, Canada, and dozens of other markets. Oral semaglutide (Rybelsus) is also widely approved. It has the broadest global footprint.

Tirzepatide is approved for weight management (as Zepbound) and type 2 diabetes (as Mounjaro) in the US, EU, and several other markets. Its global availability continues to expand.

Mazdutide is approved only in China, for both weight management and type 2 diabetes. Innovent Biologics and Eli Lilly (who holds ex-China rights) have not yet filed for approval in Western markets. Global Phase 3 trials are underway or planned, including a head-to-head study against tirzepatide.

The practical implication is that mazdutide is not an option outside China in 2026. For patients in Western markets, the relevant comparison remains semaglutide vs tirzepatide, with tirzepatide showing a clear advantage in weight loss magnitude based on the SURMOUNT-5 head-to-head data.^[5] Mazdutide's entry into Western markets, if and when it occurs, will add a third option with a distinct mechanism that could prove particularly valuable for patients with concurrent fatty liver disease.

The Bottom Line

Mazdutide, semaglutide, and tirzepatide all reduce body weight through GLP-1 receptor activation, but their second targets differ: glucagon for mazdutide, GIP for tirzepatide, and none for semaglutide. Phase 3 data shows mazdutide 9 mg achieving approximately 20% weight loss, comparable to tirzepatide's best results and exceeding semaglutide. Head-to-head data against semaglutide favors mazdutide on both glycemic control and weight loss, though at a non-equivalent semaglutide dose. All comparisons are limited by the fact that mazdutide has only been tested in Chinese populations, while semaglutide and tirzepatide trials enrolled primarily Western participants.

Frequently Asked Questions

Is mazdutide better than semaglutide for weight loss?

In the DREAMS-3 head-to-head trial, mazdutide 6 mg produced 10.29% weight loss versus 6.00% for semaglutide 1 mg at 32 weeks. The semaglutide dose used was the diabetes dose (1 mg), not the higher obesity dose (2.4 mg). At similar maximum efficacy comparisons, mazdutide 9 mg (20.1% at 60 weeks) appears to exceed semaglutide 2.4 mg (14.9% at 68 weeks), though these are cross-trial comparisons with different populations.

How does mazdutide compare to tirzepatide?

No head-to-head trial has been completed. Cross-trial data suggests similar weight loss at maximum doses: mazdutide 9 mg produced 20.1% loss at 60 weeks in Chinese adults, while tirzepatide 15 mg produced 22.5% at 72 weeks in predominantly Western adults. Their mechanisms differ: mazdutide targets GLP-1 plus glucagon, while tirzepatide targets GLP-1 plus GIP. A direct comparison trial is planned.

What makes mazdutide different from other GLP-1 drugs?

Mazdutide is the first approved drug to activate both GLP-1 and glucagon receptors. While GLP-1 suppresses appetite and slows gastric emptying, glucagon receptor activation increases energy expenditure and promotes hepatic fat oxidation. This dual mechanism may be particularly beneficial for patients with fatty liver disease, offering metabolic effects that pure GLP-1 agonists do not provide.

Is mazdutide available in the United States?

No. As of early 2026, mazdutide is approved only in China for both weight management and type 2 diabetes. Eli Lilly holds ex-China commercial rights, but no FDA filing has been made. Global Phase 3 trials are underway. US availability depends on successful completion of these trials and regulatory submission, with no firm timeline announced.

Does mazdutide raise blood sugar since it activates glucagon?

Despite glucagon's role in raising blood glucose, mazdutide's net effect is glucose-lowering. The GLP-1 component enhances insulin secretion and suppresses glucagon release from the pancreas, offsetting the glucagon receptor's hyperglycemic effect. In the DREAMS-3 trial, mazdutide reduced HbA1c by 2.03%, actually exceeding semaglutide's reduction of 1.84% in T2D patients.

What are the side effects of mazdutide compared to semaglutide?

Both drugs share similar gastrointestinal side effects: nausea, vomiting, diarrhea, and decreased appetite. These are most common during dose escalation and typically resolve. In the GLORY-1 trial, over 90% of mazdutide participants completed treatment, suggesting manageable tolerability. Mazdutide has a shorter safety track record (approved 2024) compared to semaglutide (in clinical use since 2017).