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Mazdutide: GLP-1/Glucagon Dual Agonist

The global obesity epidemic has driven an explosion of interest in peptide therapeutics that can deliver substantial, sustained weight loss.

The global obesity epidemic has driven an explosion of interest in peptide therapeutics that can deliver substantial, sustained weight loss. While GLP-1 receptor agonists like semaglutide and tirzepatide have made headlines with their impressive clinical results, a new category of dual agonists is emerging. Mazdutide represents the first approved member of this class—a peptide that simultaneously activates both GLP-1 and glucagon receptors. This dual mechanism offers a fundamentally different approach to metabolic regulation, combining appetite suppression with increased energy expenditure. In June 2025, mazdutide became the world's first GLP-1/glucagon dual receptor agonist approved for weight management, marking a significant milestone in peptide therapeutics.

This article examines the mechanisms, clinical evidence, and regulatory status of mazdutide, providing a comprehensive overview of what the research shows about this novel dual agonist.

Table of Contents

Quick Facts

PropertyDetail
Full NameMazdutide
Other NamesIBI362, LY3305677, OXM-3
TypeDual GLP-1R/GCGR agonist; oxyntomodulin analog
Molecular Weight4,563.06 Da
Molecular FormulaC₂₁₀H₃₂₂N₄₆O₆₇
ManufacturerInnovent Biologics (China); Eli Lilly (Western markets)
Half-Life8-10 days
AdministrationOnce-weekly subcutaneous injection
FDA StatusPhase 2 (expected decision 2028-2029)
Other ApprovalsApproved in China (June 2025 for weight management, September 2025 for type 2 diabetes)
CAS Number2259884-03-0

What Is Mazdutide?

Mazdutide is a synthetic peptide analog of oxyntomodulin, a naturally occurring gut hormone that activates both glucagon-like peptide-1 (GLP-1) and glucagon receptors. Unlike single-target GLP-1 agonists such as semaglutide or liraglutide, mazdutide acts on two distinct receptor systems simultaneously. This dual mechanism sets it apart from other metabolic peptides currently in clinical use.

The peptide was developed by Innovent Biologics and is licensed to Eli Lilly for development in Western markets. It is also referred to by its research designations IBI362 (Innovent) and LY3305677 (Lilly). The compound has been structurally modified with a fatty-acyl moiety to extend its half-life, enabling convenient once-weekly dosing.

Mazdutide belongs to an emerging class of multi-agonist peptides designed to target obesity and metabolic dysfunction through complementary pathways. While drugs like tirzepatide combine GLP-1 with GIP (glucose-dependent insulinotropic polypeptide) activation, mazdutide instead pairs GLP-1 with glucagon receptor stimulation—a combination that offers distinct metabolic effects, particularly regarding energy expenditure.

In June 2025, mazdutide received its first regulatory approval from China's National Medical Products Administration (NMPA) for chronic weight management in adults with a BMI of ≥28 kg/m² or ≥24 kg/m² with weight-related comorbidities. Three months later, it also received approval in China for glycemic control in adults with type 2 diabetes. The drug is marketed as Xinermei® in China.

How Mazdutide Works: Mechanisms of Action

Mazdutide's therapeutic effects arise from simultaneous activation of two hormone receptor pathways that regulate energy balance, glucose metabolism, and appetite. This dual mechanism distinguishes it from single-target GLP-1 agonists and provides complementary effects on body weight and metabolic health.

GLP-1 Receptor Activation

The GLP-1 receptor component of mazdutide functions similarly to established drugs like semaglutide and exenatide. When mazdutide binds to GLP-1 receptors, it triggers several metabolic responses:

  • Appetite suppression: GLP-1 receptor activation in the hypothalamus reduces hunger signaling and promotes satiety, leading to decreased food intake.
  • Slowed gastric emptying: The peptide delays stomach emptying, prolonging the feeling of fullness after meals.
  • Enhanced insulin secretion: GLP-1 stimulation increases glucose-dependent insulin release from pancreatic beta cells.
  • Reduced glucagon secretion: GLP-1 receptor activation suppresses glucagon release from pancreatic alpha cells when glucose levels are elevated.

These effects collectively reduce caloric intake and improve glycemic control, mechanisms well-established in the pharmacology of GLP-1-based therapeutics.

Glucagon Receptor Activation

The glucagon receptor component is what makes mazdutide distinctive. Glucagon is traditionally viewed as a counter-regulatory hormone that raises blood glucose, which might seem counterproductive in treating obesity and diabetes. However, glucagon receptor activation offers several metabolic benefits when balanced with GLP-1 signaling:

  • Increased energy expenditure: Glucagon receptor stimulation increases metabolic rate and promotes thermogenesis, enhancing calorie burning.
  • Improved hepatic fat metabolism: Glucagon activation stimulates fatty acid oxidation in the liver and reduces hepatic lipid accumulation, addressing metabolic dysfunction-associated steatotic liver disease (MASLD).
  • Enhanced lipolysis: Glucagon promotes the breakdown of stored fat into free fatty acids for energy use.

Balancing Two Pathways

The potential concern with glucagon receptor activation—elevated blood glucose—is counteracted by the simultaneous GLP-1 receptor stimulation. The GLP-1 component enhances insulin secretion and suppresses inappropriate glucagon release in response to meals, preserving glycemic control while allowing the metabolic benefits of glucagon to manifest. This balance is a key feature of mazdutide's design.

Research published in eBioMedicine also identified neuroprotective effects in preclinical models, with dual receptor activation engaging distinct pathways related to neurotransmission, oxidative stress, and neuroinflammation. While these findings require further clinical investigation, they suggest the dual agonist approach may have effects beyond weight and glucose regulation.

The extended half-life of mazdutide, achieved through structural modifications including fatty acid conjugation, supports once-weekly administration. Peak plasma concentrations are reached approximately 72 hours after injection, with steady-state levels achieved after four weeks of weekly dosing.

Clinical Research and Trial Results

Mazdutide has undergone extensive clinical evaluation through multiple phases of development, with the majority of large-scale studies conducted in Chinese populations. The data demonstrate dose-dependent effects on body weight, glycemic control, and cardiometabolic markers.

Phase 1 Studies

Early dose-ranging studies established the safety and pharmacokinetics of mazdutide at doses up to 16 mg weekly. A Phase 1 trial published in Diabetes, Obesity and Metabolism examined high-dose mazdutide (up to 16 mg) in adults with overweight or obesity. At Week 20, mean body weight reductions were -20.0% in one cohort and -21.0% in another, compared to -0.1% with placebo. Weight loss of ≥15% was achieved by 66.7% and 75.0% of participants in the two high-dose cohorts.

Another Phase 1b study evaluated 9 mg and 10 mg doses in Chinese adults with overweight or obesity, demonstrating mean body weight reductions of -11.7% at week 12 for the 9 mg dose and -9.5% at week 16 for the 10 mg dose, according to research published in eClinicalMedicine.

Phase 2 Studies

Phase 2 trials examined mazdutide across multiple indications, establishing efficacy in both metabolic dysfunction and weight management.

A randomized controlled trial published in Nature Communications evaluated 24-week treatment with mazdutide up to 6 mg in Chinese adults with overweight or obesity. The study showed clinically meaningful dose-dependent weight reduction and improvements in multiple cardiometabolic risk factors, with gastrointestinal side effects being mostly mild to moderate.

In patients with type 2 diabetes, a Phase 2 study published in Diabetes Care demonstrated that 20-week treatment with mazdutide produced clinically meaningful glycemic control with HbA1c reductions ranging from -1.41% to -1.67%, along with dose-dependent body weight reductions reaching up to -7.1%.

Phase 3 GLORY Program (Weight Management)

The GLORY clinical trial program represents the most comprehensive evaluation of mazdutide for weight management.

GLORY-1 Trial

The pivotal GLORY-1 study, published in the New England Journal of Medicine, randomized Chinese adults with a BMI ≥28 or BMI 24-28 with weight-related comorbidities to receive 4 mg mazdutide, 6 mg mazdutide, or placebo for 48 weeks.

Results at Week 48:

  • Mean percentage change in body weight: -11.00% (4 mg), -14.01% (6 mg), -0.30% (placebo)
  • Participants achieving ≥15% weight loss: 35.7% (4 mg), 49.5% (6 mg), 2.0% (placebo)
  • Participants achieving ≥5% weight loss: 73.9% (4 mg), 82.0% (6 mg), 10.5% (placebo)

The study also showed substantial reductions in liver fat content. Among participants with baseline liver fat ≥10%, the mean percent change in liver fat content was -65.85% (4 mg), -80.24% (6 mg), and -5.27% (placebo).

Discontinuation rates due to adverse events were exceptionally low: 1.5% (4 mg), 0.5% (6 mg), and 1.0% (placebo).

GLORY-2 Trial

GLORY-2 evaluated a higher 9 mg dose in adults with obesity (BMI ≥30 kg/m²) over 60 weeks.

Results at Week 60:

  • Mean weight reduction: 18.55% (9 mg) vs. 3.02% (placebo)
  • Participants achieving ≥20% weight loss: 44.0% (9 mg) vs. 2.6% (placebo)

Among participants with baseline liver fat ≥10%, liver fat content decreased by -71.9% with mazdutide 9 mg compared to +5.1% with placebo.

GLORY-3 and GLORY-OSA

The GLORY program also includes ongoing Phase 3 trials comparing mazdutide versus semaglutide in adults with overweight or obesity accompanied by metabolic-associated fatty liver disease (GLORY-3), and a trial in participants with obstructive sleep apnea and obesity (GLORY-OSA).

Phase 3 DREAMS Program (Type 2 Diabetes)

The DREAMS clinical program evaluated mazdutide in patients with type 2 diabetes.

DREAMS-1

DREAMS-1 examined mazdutide monotherapy in Chinese adults with untreated type 2 diabetes. Results published in Nature showed significant HbA1c reductions of -1.57% (4 mg) and -2.15% (6 mg) at week 24, compared to minimal changes with placebo. Body weight reductions were -5.61% (4 mg) and -7.81% (6 mg) versus +0.12% with placebo.

DREAMS-3: Head-to-Head vs. Semaglutide

The most notable diabetes trial was DREAMS-3, the first Phase 3 head-to-head comparison of a GLP-1/glucagon dual agonist against semaglutide. Results announced in 2025 demonstrated superiority on the primary endpoint.

At Week 32:

  • Combined endpoint (HbA1c <7.0% and ≥10% weight loss): 48.0% (mazdutide) vs. 21.0% (semaglutide), p<0.0001
  • Mean HbA1c reduction: -2.03% (mazdutide) vs. -1.84% (semaglutide)
  • Mean weight loss: -10.29% (mazdutide) vs. -6.0% (semaglutide)

DREAMS-2

DREAMS-2 compared mazdutide versus dulaglutide in Chinese adults with type 2 diabetes who had poor glycemic control with oral medications. Results showed mazdutide outperformed dulaglutide on both glycemic control and weight loss measures.

Meta-Analyses

A systematic review and meta-analysis published in Frontiers in Endocrinology examined seven randomized controlled trials involving 680 participants. The analysis found that mazdutide produced significantly greater weight loss than placebo (mean difference -6.22%). Participants without diabetes experienced greater weight loss (mean difference -8.44%) compared to those with diabetes (mean difference -3.55%).

Safety Profile and Side Effects

Mazdutide's safety profile resembles that of established GLP-1 receptor agonists, with gastrointestinal symptoms being the most common adverse events. Data from multiple clinical trials provide a consistent picture of tolerability across different doses and populations.

Common Side Effects

Gastrointestinal adverse events are the predominant side effects, occurring more frequently during dose escalation and typically declining over time. According to meta-analysis data, the most common adverse events include:

  • Diarrhea: 36%
  • Decreased appetite: 29%
  • Nausea: 23%
  • Vomiting: 14%

These symptoms were mostly mild to moderate in severity and transient in nature. Importantly, discontinuation rates due to adverse events were comparable to placebo in most studies, suggesting that while gastrointestinal effects are common, they are generally manageable.

Research published in Diabetes Care noted that diarrhea, nausea, and vomiting showed no clear association with mazdutide dose. An interesting ethnic difference was observed: diarrhea was the most commonly reported gastrointestinal symptom in studies with Chinese populations, whereas nausea has been more frequent with GLP-1 receptor agonists in Western populations.

Cardiovascular Effects

All participants receiving mazdutide experienced increases in heart rate, attributed to the glucagon receptor activity of the drug. This effect is consistent with the known cardiovascular effects of glucagon stimulation. The clinical significance of these heart rate increases in long-term use requires further evaluation.

Hypoglycemia

Hypoglycemia occurred in approximately 10% of participants in clinical trials. This rate is generally lower than seen with insulin or sulfonylureas, likely because GLP-1-mediated insulin secretion is glucose-dependent, reducing the risk of excessive insulin release when blood glucose is normal.

Serious Adverse Events

Rare but potentially serious side effects noted in clinical development include:

  • Gallbladder disease: Increased risk has been observed with GLP-1 receptor agonists as a class, likely related to changes in bile composition and gallbladder motility.
  • Pancreatitis: While uncommon, pancreatitis has been reported with GLP-1-based therapies and remains a consideration.
  • Gastroparesis concerns: Effects on gastric emptying may necessitate safety precautions during anesthesia and surgical procedures.

Contraindications

Based on current data, mazdutide should not be used in:

  • Pregnancy or nursing mothers
  • Individuals with a history of medullary thyroid cancer or multiple endocrine neoplasia syndrome type 2 (consistent with GLP-1 receptor agonist class warnings)

Comprehensive prescribing information with complete contraindications and warnings is not yet publicly available for markets outside China, as the drug remains in Phase 2 development in the United States.

Long-Term Safety

The longest randomized controlled trial data extend to 60 weeks (GLORY-2), showing favorable tolerability with no new safety signals identified. As with other peptide therapeutics in this class, ongoing post-marketing surveillance and longer-term observational studies will be important for characterizing the safety profile with extended use.

Metabolic and Cardiovascular Benefits

Beyond weight loss and glycemic control, mazdutide produces improvements in multiple cardiometabolic risk factors that contribute to overall metabolic health. These effects reflect the compound's dual mechanism and its impact on both glucose and lipid metabolism.

Liver Fat Reduction

One of the most striking effects of mazdutide is its impact on hepatic steatosis. In the GLORY-1 trial, among participants with baseline liver fat content ≥10%, liver fat was reduced by -80.24% with the 6 mg dose, compared to -5.27% with placebo. More than 60% of participants on the 10 mg and 16 mg doses achieved complete steatosis resolution (liver fat <5%), compared to only 13% receiving placebo, according to a Phase 2 MASLD trial.

These results position mazdutide as a promising therapy for metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD). The glucagon receptor activation component likely contributes significantly to these liver benefits by enhancing hepatic fatty acid oxidation and reducing lipid accumulation.

Lipid Profile Improvements

Mazdutide treatment produces favorable changes in blood lipids. In a case study published in Frontiers in Endocrinology, lipid profiles improved markedly:

  • Total cholesterol: Decreased from 6.08 mmol/L to 5.25 mmol/L (-13.65%)
  • Triglycerides: Decreased from 1.84 mmol/L to 0.57 mmol/L (-69.02%)
  • HDL cholesterol: Increased from 1.05 mmol/L to 1.29 mmol/L

These lipid changes reduce cardiovascular risk and complement the benefits seen with weight loss and improved glycemic control.

Blood Pressure Reduction

Clinical trials have consistently shown reductions in blood pressure with mazdutide treatment. According to research in Nature Communications, mazdutide produced marked reductions in systolic blood pressure alongside improvements in other cardiometabolic markers. The mechanisms likely involve direct vascular effects of GLP-1 receptor activation, reduced sympathetic nervous system activity, and the indirect benefits of weight loss.

Insulin Sensitivity

Mazdutide significantly improves insulin sensitivity, a key feature of metabolic health. Research published in Diabetes Care demonstrated that mazdutide reduced fasting insulin concentrations by -24.0% and -44.9% compared to placebo's increase of +50.7%. Reductions in fasting glucose, proinsulin, C-peptide, and HbA1c levels further confirmed improvements in glycemic control and insulin sensitivity.

Uric Acid Reduction

Mazdutide reduces serum uric acid levels, which may benefit individuals with hyperuricemia or gout. A case report in Frontiers in Endocrinology documented improvements in an adolescent with obesity, type 2 diabetes, and hyperuricemia treated with mazdutide. The mechanisms behind this effect may involve increased renal uric acid excretion and improvements in insulin resistance, which can affect uric acid metabolism.

Waist Circumference Reduction

Significant reductions in waist circumference accompany weight loss with mazdutide, indicating preferential loss of visceral adipose tissue. Visceral fat is metabolically active and strongly associated with insulin resistance, dyslipidemia, and cardiovascular disease, making its reduction particularly beneficial for metabolic health.

Mazdutide's regulatory pathway differs significantly between China and Western markets, reflecting its development history and partnership structure.

China Approval

In June 2025, mazdutide received its first regulatory approval from China's National Medical Products Administration (NMPA) for chronic weight management. The approval announcement marked mazdutide as the world's first dual GLP-1/glucagon receptor agonist approved for weight management.

The indication covers use in combination with diet control and increased physical activity for long-term body weight management in adults with:

  • BMI ≥28 kg/m², or
  • BMI ≥24 kg/m² with one or more weight-related comorbidities

In September 2025, mazdutide also received approval in China for glycemic control in adults with type 2 diabetes. The drug is marketed as Xinermei® by Innovent Biologics in China.

United States Development

Mazdutide is currently in Phase 2 development in the United States. According to regulatory tracking sources, Eli Lilly is conducting Phase 2 trials in patients with overweight or obesity, primarily using U.S. sites with 179 participants enrolled.

The expected FDA decision timeline is approximately 2028-2029. Before approval, Eli Lilly must complete ongoing Phase 2 trials, analyze results, and design and execute Phase 3 pivotal trials demonstrating safety and efficacy in U.S. populations comparable to the GLORY-1 results achieved in China.

Development Partnership

Innovent entered into an exclusive license agreement with Eli Lilly in 2019 for the development and commercialization of mazdutide. Under this arrangement:

  • Innovent holds development and commercialization rights in China
  • Eli Lilly maintains rights to mazdutide outside of China

This partnership extends a decade-long collaboration between the two companies and reflects an increasingly common model for global drug development where regional expertise and market access are optimized through licensing agreements.

Other Markets

Regulatory submissions in markets outside China and the United States have not been publicly announced. Given the drug's current development stage in Western markets, approvals in Europe, Canada, and other regions would likely follow U.S. regulatory action by several years.

Compound Classification

As a prescription peptide therapeutic, mazdutide is subject to standard pharmaceutical regulations. It is not a dietary supplement, research chemical, or substance available for personal use outside approved medical contexts. In countries where it is not approved, it remains an investigational drug limited to clinical trial use.

Mazdutide vs Other GLP-1 Drugs

Understanding how mazdutide compares to established GLP-1-based therapies helps contextualize its place in the evolving landscape of metabolic therapeutics. Several key differences distinguish this dual agonist from single-target and other multi-agonist drugs.

Mazdutide vs Semaglutide

Semaglutide is a selective GLP-1 receptor agonist available as both a weekly injection (Ozempic/Wegovy) and a daily oral tablet (Rybelsus). The DREAMS-3 trial provided direct head-to-head comparison data in patients with type 2 diabetes and obesity.

At 32 weeks, mazdutide demonstrated superior efficacy on the combined endpoint: 48.0% of mazdutide participants achieved both HbA1c <7.0% and ≥10% weight loss versus 21.0% with semaglutide. Mean HbA1c reduction was -2.03% with mazdutide compared to -1.84% with semaglutide, and mean weight loss was -10.29% versus -6.0%.

The mechanism differs fundamentally: semaglutide acts solely through GLP-1 receptor activation, while mazdutide adds glucagon receptor stimulation for increased energy expenditure and enhanced hepatic fat metabolism. Side effect profiles are similar, both dominated by gastrointestinal symptoms.

Mazdutide vs Tirzepatide

Tirzepatide is also a dual agonist, but it combines GLP-1 receptor activation with glucose-dependent insulinotropic polypeptide (GIP) receptor stimulation—a different second target than mazdutide's glucagon receptor approach.

Weight loss data show tirzepatide with a slight edge: up to 22.5% weight loss in global trials at the 15 mg dose compared to mazdutide's 18.55% at 9 mg (though in Chinese populations only). In Chinese trials specifically, tirzepatide achieved approximately 17.5% weight loss at 15 mg at 48 weeks, while mazdutide achieved 14.01% at 6 mg at 48 weeks.

The mechanistic difference is significant. GIP receptor activation enhances insulin secretion and may affect fat storage and adipose tissue function. Glucagon receptor activation increases energy expenditure and promotes hepatic fat oxidation. Both approaches pair GLP-1 with a complementary pathway, but through different physiological mechanisms.

Tirzepatide is FDA-approved and globally available; mazdutide is approved only in China and remains in Phase 2 development in the U.S. Tirzepatide's safety profile is well-established through large global trials, while mazdutide's long-term safety data are still accumulating.

Mazdutide vs Liraglutide and Other Daily GLP-1 Agonists

Older GLP-1 receptor agonists like liraglutide and exenatide require daily or twice-daily injections due to shorter half-lives. Mazdutide's once-weekly administration offers convenience comparable to semaglutide and dulaglutide.

Weight loss efficacy with daily GLP-1 agonists is generally lower—liraglutide produces approximately 5-8% weight loss—compared to mazdutide's 14-18% depending on dose. This reflects both the dual mechanism of mazdutide and the advantages of sustained receptor activation with long-acting formulations.

Mazdutide vs Next-Generation Multi-Agonists

Several other dual and triple agonists are in development. Retatrutide is a triple agonist targeting GLP-1, GIP, and glucagon receptors, combining mazdutide's glucagon component with tirzepatide's GIP component. Survodutide is another dual agonist pairing GLP-1 with glucagon. CagriSema combines semaglutide with cagrilintide, an amylin analog.

These compounds are at various stages of development, and head-to-head comparisons are limited. Mazdutide's approval in China gives it a first-to-market advantage in the GLP-1/glucagon dual agonist category, though competition in this space will intensify as other compounds advance through clinical development.

Frequently Asked Questions

Is mazdutide available in the United States?

No. Mazdutide is currently in Phase 2 clinical trials in the United States, with an expected FDA decision around 2028-2029. It is approved only in China as of 2025.

How much weight can you lose with mazdutide?

Clinical trial results show dose-dependent weight loss ranging from 11-14% at 48 weeks with 4-6 mg doses, and 18.55% at 60 weeks with the 9 mg dose. Higher experimental doses (16 mg) produced approximately 20-21% weight loss at 20 weeks in Phase 1 studies. Individual results vary based on baseline weight, adherence, lifestyle factors, and metabolic characteristics.

How does mazdutide differ from Ozempic or Wegovy?

Mazdutide is a dual agonist that activates both GLP-1 and glucagon receptors, while Ozempic/Wegovy (semaglutide) activates only GLP-1 receptors. The glucagon component adds increased energy expenditure and enhanced liver fat metabolism to the appetite suppression and glycemic effects of GLP-1 activation. Head-to-head trial data showed mazdutide produced greater weight loss and HbA1c reduction than semaglutide in patients with type 2 diabetes.

What are the most common side effects?

Gastrointestinal symptoms are most common: diarrhea (36%), decreased appetite (29%), nausea (23%), and vomiting (14%). These effects are typically mild to moderate, occur more frequently during dose escalation, and tend to diminish over time. Discontinuation rates due to side effects were similar to placebo in most studies.

Does mazdutide cause heart rate increases?

Yes. All participants in clinical trials experienced increases in heart rate, attributed to the glucagon receptor activity of the drug. The clinical significance of this effect with long-term use requires further evaluation.

Can mazdutide reverse fatty liver disease?

Clinical trial data show substantial reductions in liver fat content. Among participants with baseline liver fat ≥10%, mazdutide reduced liver fat by 65-80% depending on dose. More than 60% of participants on higher doses achieved complete resolution of steatosis (liver fat <5%). These results suggest significant potential for treating metabolic dysfunction-associated steatotic liver disease (MASLD).

Is mazdutide better than Mounjaro (tirzepatide)?

Direct head-to-head comparison data are not available. Global trial data show tirzepatide achieving up to 22.5% weight loss at 15 mg, while mazdutide achieved 18.55% at 9 mg in Chinese populations. The drugs use different dual mechanisms—mazdutide targets GLP-1/glucagon while tirzepatide targets GLP-1/GIP. Both are effective; the optimal choice may depend on individual patient characteristics, tolerability, and specific metabolic goals once both are available in the same markets.

How is mazdutide administered?

Mazdutide is administered as a once-weekly subcutaneous injection, typically in the abdominal area, using a prefilled autoinjector pen. The dosing schedule is similar to semaglutide and other long-acting GLP-1 receptor agonists.

Who should not take mazdutide?

Based on available data, mazdutide should not be used in pregnant or nursing women, or in individuals with a history of medullary thyroid cancer or multiple endocrine neoplasia syndrome type 2. Complete contraindication information for markets outside China is not yet available as the drug remains investigational in most countries.

The Bottom Line

Mazdutide represents a meaningful advance in peptide-based metabolic therapeutics, distinguished by its dual GLP-1/glucagon receptor mechanism. By combining appetite suppression and enhanced insulin secretion (via GLP-1) with increased energy expenditure and improved hepatic fat metabolism (via glucagon), the peptide offers a differentiated approach to weight management and glycemic control.

Clinical trial data are compelling. Weight loss of 14-18% with approved doses compares favorably to first-generation GLP-1 agonists and approaches the efficacy of the most potent available therapies. Head-to-head comparison against semaglutide showed superiority for both weight loss and glycemic control in patients with type 2 diabetes. The particularly striking reductions in liver fat—up to 80% in some cohorts—position mazdutide as a potential therapy for metabolic dysfunction-associated steatotic liver disease.

Safety data through 60 weeks show a tolerability profile consistent with established GLP-1 receptor agonists. Gastrointestinal side effects are common but generally mild to moderate, and discontinuation rates were low. The heart rate increases observed with glucagon receptor activation warrant ongoing monitoring, though no serious cardiovascular safety signals have emerged in trials to date.

The regulatory status limits current access. Approval in China provides a proof of concept for commercial viability, but the drug remains in Phase 2 development in the United States with approval likely several years away. The development partnership between Innovent and Eli Lilly suggests confidence in the compound's potential, but competition in this space is intensifying with multiple dual and triple agonists in various stages of clinical development.

For researchers, clinicians, and patients monitoring developments in metabolic therapeutics, mazdutide warrants attention as the first approved member of the GLP-1/glucagon dual agonist class. Whether it will achieve the same commercial success and clinical adoption as drugs like semaglutide and tirzepatide depends on forthcoming Phase 3 data in Western populations, long-term safety surveillance, pricing strategies, and the competitive landscape when it reaches broader markets.

The science is sound. The mechanism is rational. The clinical data are encouraging. The question now is whether mazdutide's advantages over existing therapies are sufficient to carve out a significant role in a crowded and rapidly evolving market.

This article is for educational purposes only. PeptideJournal.org does not sell peptides, provide medical advice, or recommend the use of any unapproved substances. Always consult a qualified healthcare provider before making decisions about your health.

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  15. Fierce Pharma. With China approval, Lilly and Innovent's mazdutide breaks into new class for GLP-1 obesity drugs. 2025. Available at: https://www.fiercepharma.com/pharma/china-approval-lilly-and-innovents-mazdutide-breaks-new-class-glp-1-obesity-drugs

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  19. Innovent Biologics. Nature: Two Phase 3 Clinical Results of Mazdutide (GLP-1/GCG Dual Receptor Agonist) in Chinese Adults with Type 2 Diabetes Have Been Back-to-Back Published in Nature. PR Newswire, 2025. Available at: https://www.prnewswire.com/news-releases/nature--two-phase-3-clinical-results-of-mazdutide-glp-1gcg-dual-receptor-agonist-in-chinese-adults-with-type-2-diabetes-have-been-back-to-back-published-in-nature-302644606.html

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