Mazdutide: Dual GLP-1/Glucagon Agonist Research, GLORY Trials & Weight Studies

This material is for informational and research purposes only. It is not intended as medical advice and does not constitute a recommendation for human use. Always consult qualified professionals before making any decisions related to peptide research.

What Is Mazdutide?

Mazdutide, also known by its research designation IBI362, is a synthetic peptide classified as a dual GLP-1/glucagon receptor agonist. It was developed by Innovent Biologics, a Chinese biopharmaceutical company, in collaboration with Eli Lilly and Company. The partnership represents a significant example of cross-border pharmaceutical development, with Innovent retaining rights for the Chinese market while Lilly holds rights for markets outside China.

Structurally, mazdutide is an oxyntomodulin analogue — a modified version of the naturally occurring gut hormone oxyntomodulin, which natively activates both the GLP-1 and glucagon receptors. Native oxyntomodulin has an extremely short circulating half-life, rendering it impractical for research applications requiring sustained receptor activation. Mazdutide incorporates deliberate molecular modifications to overcome this limitation, including fatty acid acylation that promotes albumin binding and extends its pharmacokinetic profile, enabling once-weekly administration in clinical research protocols.

The peptide has attracted significant research interest as part of a broader wave of multi-receptor agonists that extend beyond the GLP-1-only paradigm established by compounds like semaglutide. By combining GLP-1 receptor agonism with glucagon receptor activation, mazdutide is being investigated for its potential to address metabolic endpoints through complementary mechanistic pathways. As of early 2026, mazdutide is in advanced Phase 3 clinical development in China through the GLORY trial program, with regulatory submissions anticipated in the near term.

Mechanism of Action: Dual Receptor Agonism

Mazdutide’s pharmacological profile is defined by its simultaneous activation of two distinct receptor systems involved in metabolic regulation. Understanding these pathways individually and their potential synergistic interaction is essential context for interpreting the published clinical data.

GLP-1 Receptor Activation

The glucagon-like peptide-1 (GLP-1) receptor is widely expressed in the pancreas, central nervous system, gastrointestinal tract, and cardiovascular system. GLP-1 receptor agonism has been extensively studied over the past two decades and is associated with several well-characterized downstream effects in published research:

• Appetite regulation — GLP-1 receptor activation in hypothalamic and brainstem nuclei has been observed to reduce appetite and caloric intake in both preclinical and clinical studies. This satiety signaling is considered a primary driver of the body weight changes observed with GLP-1 receptor agonists.
• Delayed gastric emptying — GLP-1 receptor agonism slows the rate of gastric emptying, which research suggests extends postprandial satiety and modulates the glycemic response to meals.
• Glucose-dependent insulin secretion — Activation of GLP-1 receptors on pancreatic beta cells has been shown to potentiate insulin release in a glucose-dependent manner, meaning the insulinotropic effect is attenuated at normal glucose levels, reducing the risk of hypoglycemia in research settings.
• Glucagon suppression — Paradoxically, GLP-1 receptor activation suppresses glucagon secretion from pancreatic alpha cells. In the context of mazdutide, this creates an interesting dynamic with the compound’s direct glucagon receptor agonism.

Glucagon Receptor Activation

The glucagon receptor (GCGR) is predominantly expressed in the liver, with additional expression in adipose tissue, kidneys, and other metabolic organs. The inclusion of glucagon receptor agonism in mazdutide’s profile represents a deliberate strategy to engage energy expenditure pathways that GLP-1-only agonists do not directly activate:

• Increased energy expenditure — Glucagon receptor activation has been associated in research with elevated resting metabolic rate, potentially through stimulation of hepatic thermogenesis and activation of brown adipose tissue. This mechanism is hypothesized to complement the appetite-reducing effects of GLP-1 agonism by simultaneously increasing caloric output.
• Hepatic lipid oxidation — Glucagon signaling in the liver promotes the oxidation of fatty acids and reduces hepatic lipid accumulation. This pathway is of particular interest in research related to metabolic dysfunction-associated steatotic liver disease (MASLD, formerly NAFLD/NASH), where hepatic fat reduction is a primary therapeutic target.
• Amino acid metabolism — Glucagon receptor activation influences amino acid catabolism in the liver, a pathway that has been linked to the regulation of circulating amino acid levels and hepatic ureagenesis.

The Dual Agonism Hypothesis

The rationale for combining GLP-1 and glucagon receptor agonism rests on the hypothesis that the two pathways produce complementary metabolic effects. GLP-1 agonism primarily reduces caloric intake through central appetite suppression and peripheral glucose regulation. Glucagon agonism, by contrast, primarily increases caloric expenditure through hepatic and thermogenic mechanisms. The theoretical result is an approach that modifies both sides of the energy balance equation simultaneously.

A key pharmacological challenge in dual agonist design is balancing the glucose-lowering effects of GLP-1 activation against the glucose-raising tendency of glucagon receptor stimulation. Mazdutide’s receptor potency ratio is engineered such that the GLP-1 component predominates sufficiently to maintain glycemic control while still permitting meaningful glucagon-mediated metabolic effects. Published Phase 2 data, discussed below, suggest that this balance has been achieved in clinical settings, with observed HbA1c reductions despite the glucagon agonist component.

Clinical Trial Data

Mazdutide’s clinical development program is centered on the GLORY trial series, a set of Phase 2 and Phase 3 studies conducted primarily in China. The following sections summarize the key published findings from these trials.

Phase 2 Studies

The Phase 2 program for mazdutide evaluated multiple dose levels across populations with obesity and type 2 diabetes. A randomized, double-blind, placebo-controlled Phase 2 trial enrolled participants with obesity (BMI ≥ 28 kg/m² by Chinese criteria) and assessed mazdutide at doses of 3 mg, 4.5 mg, and 6 mg administered subcutaneously once weekly over 24 weeks.

Key findings from the Phase 2 obesity trial included:

• Body weight reduction — Participants in the highest dose group (6 mg) achieved mean body weight reductions in the range of 15-17% from baseline over the 24-week treatment period. Lower dose groups showed dose-dependent effects, with the 3 mg and 4.5 mg cohorts achieving progressively lower weight reductions.
• Glycemic parameters — In parallel studies enrolling participants with type 2 diabetes, mazdutide demonstrated significant HbA1c reductions across dose groups, confirming that the GLP-1 component maintains glycemic efficacy despite the concurrent glucagon receptor activation.
• Metabolic markers — Improvements in secondary endpoints including waist circumference, fasting insulin levels, and lipid profiles were observed across dose groups, though these findings require confirmation in larger Phase 3 populations.

The Phase 2 data established mazdutide’s dose-response profile and informed dose selection for the subsequent Phase 3 GLORY program. The results were presented at major diabetes and endocrinology conferences in 2023 and 2024, generating significant attention in the metabolic research community.

Phase 3: The GLORY Program

The GLORY (GLP-1/Glucagon Receptor Agonist StudY) program represents mazdutide’s pivotal clinical development phase. Multiple GLORY trials are being conducted, each targeting a specific patient population or indication.

GLORY-1

GLORY-1 is a Phase 3 trial enrolling Chinese participants with obesity (BMI ≥ 28 kg/m²) or overweight (BMI ≥ 24 kg/m²) with at least one weight-related comorbidity. The study evaluated mazdutide 6 mg and 9 mg administered once weekly versus placebo over 48 weeks.

Published results from GLORY-1 demonstrated:

• Primary endpoint — At 48 weeks, participants receiving mazdutide achieved approximately 15% mean body weight reduction from baseline, meeting the study’s primary efficacy endpoint with statistical significance versus placebo.
• Proportion achieving ≥ 5% and ≥ 10% weight loss — A substantial majority of participants in the active treatment arms achieved clinically meaningful weight loss thresholds, with response rates consistent with those observed in the Phase 2 program.
• Waist circumference — Significant reductions in waist circumference were observed, a secondary endpoint that serves as a proxy for visceral adiposity reduction.

GLORY-2 and Additional Studies

GLORY-2 is evaluating mazdutide in Chinese participants with type 2 diabetes, focusing on both glycemic control and weight management endpoints. Additional GLORY-series trials are investigating longer treatment durations, higher dose levels (up to 9 mg), and specific comorbidity populations. Several of these trials are ongoing as of early 2026, with top-line results anticipated throughout the year.

MASLD/NASH Research

Mazdutide is also being investigated for its effects on metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as NAFLD/NASH. The rationale for this research direction is grounded in the glucagon receptor component of mazdutide’s mechanism: glucagon signaling in the liver directly promotes fatty acid oxidation and may reduce hepatic steatosis through mechanisms that are complementary to the metabolic improvements driven by weight reduction alone.

Early-phase clinical data have suggested that mazdutide treatment is associated with reductions in hepatic fat content as measured by MRI-based proton density fat fraction (MRI-PDFF). These findings are consistent with preclinical observations in dual agonist research and have prompted dedicated clinical evaluation of mazdutide in MASLD populations. However, histological confirmation of liver disease improvement — the current regulatory standard for MASLD drug development — has not yet been reported from mazdutide trials.

Multi-Agonist Comparison

Mazdutide exists within a rapidly evolving landscape of multi-receptor agonist peptides. The following table provides a comparative overview of the major compounds in this class, based on published data as of early 2026. Direct cross-trial comparisons should be interpreted with caution, as differences in study populations, trial design, dose escalation schedules, and treatment duration limit the validity of head-to-head inferences.

Feature	Semaglutide	Tirzepatide	Mazdutide (IBI362)	Survodutide	Retatrutide
Developer	Novo Nordisk	Eli Lilly	Innovent Biologics / Eli Lilly	Boehringer Ingelheim	Eli Lilly
Receptor Targets	GLP-1	GLP-1 / GIP	GLP-1 / Glucagon	GLP-1 / Glucagon	GLP-1 / GIP / Glucagon
Classification	Single agonist	Dual agonist	Dual agonist	Dual agonist	Triple agonist
Administration	Once weekly SC	Once weekly SC	Once weekly SC	Once weekly SC	Once weekly SC
Max Studied Weight Loss	~15-17% (68 wk)	~22-26% (72-88 wk)	~15% (48 wk)	~19% (46 wk)	~24% (48 wk)
MASLD/NASH Data	Phase 3 positive (resmetirom approved separately)	Phase 2 positive; Phase 3 ongoing	Early clinical data; dedicated studies planned	Phase 2 positive; Phase 3 ongoing	Preclinical / early clinical
Regulatory Status	FDA/EMA approved	FDA/EMA approved	Phase 3 (China); no approval yet	Phase 3	Phase 3
Primary Trial Populations	Global	Global	Primarily China	Global	Global (U.S.-centric)
Glucagon Component	None	None	Yes (dual agonist)	Yes (dual agonist)	Yes (triple agonist)

Several observations from this comparison merit discussion. Mazdutide and survodutide share the same receptor target profile (GLP-1/glucagon dual agonism) and represent parallel approaches to the same pharmacological hypothesis. Survodutide, developed by Boehringer Ingelheim, has been studied in more geographically diverse trial populations, while mazdutide’s GLORY program has primarily enrolled Chinese participants. Whether differences in genetic background, metabolic phenotype, or BMI classification criteria between Asian and Western populations influence comparative efficacy remains an open research question.

Retatrutide, as a triple agonist adding GIP receptor activation to the GLP-1/glucagon combination, has reported the highest weight loss figures in early clinical data (~24% at 48 weeks in Phase 2). Whether the addition of GIP agonism provides clinically meaningful advantages over the dual GLP-1/glucagon approach requires confirmation in head-to-head studies, which have not been conducted to date.

Dosing in Research Protocols

The following dosing information is derived from published clinical trial protocols and is presented for research reference purposes only.

Dose Escalation Schedule

Clinical trials of mazdutide have employed a gradual dose escalation approach designed to improve gastrointestinal tolerability, consistent with standard practice across the GLP-1 receptor agonist class. The general escalation pattern observed in the GLORY program is as follows:

• Starting dose: 1.5 mg once weekly via subcutaneous injection
• Escalation to 3 mg after 4 weeks at the starting dose
• Escalation to 4.5 mg after an additional 4 weeks (optional intermediate step in some protocols)
• Escalation to 6 mg — the primary maintenance dose evaluated in Phase 3
• Escalation to 9 mg — the highest dose under evaluation in select GLORY trials

The escalation intervals (typically 4 weeks per step) are intended to allow gastrointestinal adaptation, as nausea, the most common adverse event with GLP-1 receptor agonists, tends to diminish with continued exposure at a given dose level.

Administration

Mazdutide is administered as a subcutaneous injection once weekly. In clinical trials, injection sites have included the abdomen, thigh, and upper arm, with rotation recommended between sites. The once-weekly dosing schedule is enabled by the peptide’s fatty acid acylation, which extends its circulating half-life through albumin binding.

Research Considerations

Researchers should note that the dose-response relationship for mazdutide appears to be approximately linear through the 6 mg dose level, with the 9 mg dose under evaluation for potential additional efficacy. Storage conditions, reconstitution protocols, and stability data for mazdutide research reference material may vary by supplier and formulation and should be confirmed with the specific product documentation.

Safety Profile

The safety data for mazdutide are derived from Phase 2 and Phase 3 clinical trials, which collectively represent the largest controlled datasets available as of early 2026. The following safety observations have been reported.

Gastrointestinal Adverse Events

Consistent with the broader class of GLP-1 receptor agonists, the most frequently reported adverse events with mazdutide are gastrointestinal in nature:

• Nausea — The most common adverse event, reported across all dose levels. Incidence was highest during dose escalation periods and tended to diminish with continued treatment. Rates were generally comparable to those observed with other GLP-1 receptor agonists at equivalent efficacy doses.
• Diarrhea — Reported at moderate frequency, typically transient and mild to moderate in severity.
• Vomiting — Less frequent than nausea but observed across dose groups, with higher incidence at the 6 mg and 9 mg dose levels.
• Decreased appetite — Reported as an adverse event in clinical trials, though this effect is pharmacologically expected given mazdutide’s mechanism of action.

The overall gastrointestinal tolerability profile of mazdutide has been described as consistent with the GLP-1 receptor agonist class, with no unique gastrointestinal signals attributable specifically to the glucagon receptor component. Discontinuation rates due to gastrointestinal adverse events were reported in single-digit percentages across GLORY trials.

Hepatic and Metabolic Parameters

Given mazdutide’s glucagon receptor agonist activity and its hepatic effects, liver-related safety parameters have been monitored closely in clinical trials. Published data have not identified clinically significant hepatotoxicity signals. Transient, mild elevations in liver transaminases (ALT, AST) have been observed in some participants, consistent with patterns seen across the dual agonist class, but these have generally not been accompanied by elevations in bilirubin or clinical evidence of liver injury.

Cardiovascular Safety

Heart rate increases of 2-4 beats per minute have been observed with mazdutide, a finding consistent with GLP-1 receptor agonists as a class. Dedicated cardiovascular outcome trials (CVOTs) for mazdutide have not been reported. The approved GLP-1 receptor agonists semaglutide and liraglutide have demonstrated cardiovascular benefit in large outcome trials, but whether dual GLP-1/glucagon agonists share this profile is an open research question.

Other Safety Observations

• Injection site reactions — Mild, transient injection site reactions have been reported at low frequency, consistent with subcutaneous peptide administration.
• Hypoglycemia — Clinically significant hypoglycemia has not been a prominent finding in mazdutide trials when used without concomitant insulin or sulfonylureas, consistent with the glucose-dependent mechanism of GLP-1 receptor agonism.
• Pancreatitis — As with all GLP-1 receptor agonists, pancreatitis is a monitored event. No disproportionate signal has been identified in published mazdutide data, though the total patient exposure remains limited compared to post-marketing databases for approved agents.

Limitations of Current Safety Data

It is important to acknowledge that mazdutide’s safety database, while growing, remains substantially smaller than those of approved GLP-1 receptor agonists with years of post-marketing surveillance. Rare adverse events may not be detectable in current trial populations. Long-term safety beyond 48-72 weeks has not been extensively characterized, and the implications of chronic glucagon receptor activation in combination with GLP-1 agonism require continued monitoring in ongoing and future studies.

The Chinese Pharmaceutical Development Context

Mazdutide’s development by Innovent Biologics reflects a broader trend in global pharmaceutical research: the emergence of Chinese biopharmaceutical companies as originators of novel therapeutic peptides, rather than solely as manufacturers of generic or biosimilar products. Innovent, headquartered in Suzhou, has built a pipeline of original biologics and has leveraged its partnership with Eli Lilly for both development expertise and global commercialization pathways.

The GLORY trial program’s primary enrollment in Chinese populations raises important research considerations. Obesity and type 2 diabetes prevalence patterns in East Asian populations differ from those in Western cohorts, with metabolic complications often occurring at lower BMI thresholds. Chinese regulatory criteria define obesity at BMI ≥ 28 kg/m² (compared to ≥ 30 kg/m² in Western guidelines), reflecting these population-level differences. Whether mazdutide’s efficacy and safety profiles are consistent across diverse ethnic and genetic backgrounds will require additional data from trials enrolling non-Chinese populations.

Summary

Mazdutide (IBI362) is a dual GLP-1/glucagon receptor agonist that represents one of several next-generation multi-receptor approaches in metabolic peptide research. Its mechanism combines the appetite-suppressing and glucose-lowering effects of GLP-1 receptor agonism with the energy expenditure and hepatic lipid-mobilizing effects of glucagon receptor activation. Phase 2 data demonstrating 15-17% weight loss and significant glycemic improvements, followed by Phase 3 GLORY-1 results confirming approximately 15% weight reduction at 48 weeks, have positioned mazdutide as a notable compound in the dual agonist research space.

Key research considerations include its similarity to survodutide (which shares the GLP-1/glucagon dual agonist mechanism), its primarily China-based clinical development program, its potential application in MASLD research driven by the glucagon-mediated hepatic effects, and the broader question of whether dual GLP-1/glucagon agonism offers advantages over GLP-1/GIP dual agonism (tirzepatide) or triple agonism (retatrutide) for specific metabolic endpoints.

As the GLORY program continues to generate Phase 3 data and regulatory submissions advance, mazdutide’s place within the multi-agonist landscape will become clearer. Researchers interested in the GLP-1/glucagon axis may also wish to review our guides on related compounds: semaglutide, tirzepatide, survodutide, and cagrilintide.

---

Summary of Key Research References

Study	Year	Type	Focus	Reference
Ji et al.	2022	Phase 1b RCT	GLP-1/glucagon receptor dual agonist IBI362 in type 2 diabetes patients	PMC9232612
Ji et al.	2022	Phase 1b RCT	Mazdutide (IBI362) 9 mg and 10 mg safety and efficacy in overweight/obese adults	PMC9561728
Ji et al.	2023	Phase 2 RCT	Mazdutide in Chinese overweight adults or adults with obesity	PMC10719339
He et al.	2023	Phase 2 RCT	Mazdutide efficacy and safety in type 2 diabetes patients	PMC10733643
Tian et al.	2024	Meta-Analysis	Mazdutide efficacy and safety on weight loss in diabetic and non-diabetic patients	PMC10911117
Chen et al.	2025	In Vivo	Mazdutide mitigates diabetes-associated cognitive dysfunction	PMC12205698
Liao et al.	2025	Review	Emerging concepts in obesity management: glucagon receptor agonist combinations	PMC12306892
Mazdutide Phase 1b high-dose	2025	Phase 1	Mazdutide reduces body weight in overweight/obese adults (high-dose study)	PMC12515780

This material is for informational and research purposes only. It is not intended as medical advice and does not constitute a recommendation for human use. The data summarized above are derived from published clinical trials and publicly available research. NorthPeptide supplies reference materials for authorized research use only. Always consult qualified professionals and adhere to all applicable regulations governing peptide research in your jurisdiction.

Written by NorthPeptide Research Team