What is Mazdutide?Overview
Mazdutide represents a breakthrough in metabolic disease treatment as the world's first dual GLP-1/glucagon receptor agonist approved for weight loss. While approved in China under the brand name Xinermei® in June 2025, Eli Lilly is advancing Phase 2 clinical trials in the United States for both obesity and type 2 diabetes indications.[1]
This innovative therapy works by simultaneously activating two complementary metabolic pathways—the GLP-1 receptor (which enhances insulin secretion and reduces appetite) and the glucagon receptor (which increases energy expenditure and improves fat metabolism)—offering potentially superior efficacy compared to GLP-1-only medications.[2]
- What It Is: Mazdutide (LY3305677/IBI362) is a once-weekly subcutaneous injection that activates both GLP-1 and glucagon receptors, developed through a partnership between Eli Lilly (US/global rights) and Innovent Biologics (China rights).
- Efficacy Data: The Phase 3 GLORY-1 trial demonstrated 14.8% average weight loss with the 6mg dose at 48 weeks, significantly outperforming placebo (0.5%) and showing comparable or superior results to current GLP-1-only therapies.[3]
- US Development Status: Currently in Phase 2 trials (NCT06143956) in a US-based population with obesity, with results expected to inform FDA filing timeline. China approval provides strong proof-of-concept for US regulatory pathway.[4]
How Mazdutide WorksMechanism Overview
Mazdutide is a once-weekly oxyntomodulin analogue that works through a dual-receptor mechanism, simultaneously activating both the GLP-1 receptor (GLP-1R) and the glucagon receptor (GcgR). This dual action provides complementary metabolic benefits that may exceed those achievable with GLP-1-only medications.[2]
Dual Receptor Activation
GLP-1 Receptor Pathway
The GLP-1 component of mazdutide provides well-established benefits including:
- Enhanced insulin secretion – Stimulates glucose-dependent insulin release from pancreatic beta cells
- Reduced glucagon levels – Suppresses inappropriate glucagon secretion
- Appetite suppression – Acts on brain centers to reduce hunger and food intake
- Delayed gastric emptying – Slows food passage, increasing satiety
Glucagon Receptor Pathway
The glucagon component adds unique metabolic advantages:
- Increased energy expenditure – Boosts metabolic rate and calorie burning
- Enhanced fat oxidation – Promotes breakdown of stored fat
- Improved hepatic fat metabolism – Reduces liver fat accumulation
- Visceral fat reduction – Targets harmful abdominal fat deposits[5]
While GLP-1-only medications primarily reduce appetite and food intake, mazdutide's additional glucagon receptor activation increases energy expenditure—creating a "double effect" on weight loss. Studies suggest this dual mechanism may lead to greater total body weight reduction and more favorable changes in body composition (more fat loss, less muscle loss) compared to GLP-1-only therapies.[2]
Both are dual agonists but target different receptor combinations. Tirzepatide activates GLP-1 and GIP receptors, while mazdutide activates GLP-1 and glucagon receptors. The glucagon pathway in mazdutide may provide additional benefits for energy expenditure and hepatic fat metabolism. Both show superior weight loss compared to GLP-1-only medications, though head-to-head trials are needed to determine which dual mechanism is more effective.
Clinical EvidenceTrial Results
GLORY-1 Trial: Phase 3 Weight Loss Results
The pivotal GLORY-1 trial, published in the New England Journal of Medicine in January 2025, enrolled 610 Chinese adults with overweight or obesity. Participants were randomized to receive mazdutide 4mg, 6mg, or placebo once weekly for 48 weeks, alongside diet and exercise counseling.[3]
Primary Endpoint: Mean Body Weight Reduction at 48 Weeks
Additional Efficacy Outcomes
- Clinically Significant Weight Loss (≥5%): Achieved by 35.7% of participants on mazdutide 6mg and 31.9% on 4mg, compared to minimal rates in placebo[3]
- Waist Circumference Reduction: Significant reductions observed with both doses, indicating visceral fat loss
- Metabolic Improvements: Improvements in blood pressure, lipid profiles, and glycemic control markers
Phase 2 Type 2 Diabetes Trial
A Phase 2 trial in patients with type 2 diabetes published in Diabetes Care (2024) demonstrated mazdutide's glucose-lowering efficacy. The study showed significant reductions in HbA1c and fasting plasma glucose in patients inadequately controlled on diet, exercise, or stable metformin therapy.[6]
Mazdutide's 14.8% weight loss at 48 weeks is competitive with leading GLP-1-based therapies:
- Semaglutide 2.4mg (Wegovy): ~15% at 68 weeks
- Tirzepatide 15mg (Zepbound): ~21% at 72 weeks
- Liraglutide 3mg (Saxenda): ~8% at 56 weeks
Mazdutide's results position it as a highly effective option, though direct head-to-head comparisons are needed for definitive efficacy ranking.
Safety and Side EffectsSafety Profile
Clinical trials show mazdutide's safety profile is consistent with the GLP-1 receptor agonist class, with the most common side effects being gastrointestinal in nature. Most adverse events were mild to moderate in severity and occurred primarily during the dose-escalation phase.[3]
Common Side Effects from GLORY-1 Trial
The most frequently reported adverse events were:
- Nausea – Most common, typically mild-moderate, occurring during dose escalation
- Diarrhea – Generally transient and manageable
- Vomiting – Less common than nausea, usually resolves over time
- Constipation – Reported in some participants
Discontinuation Rates (GLORY-1 Trial)
Treatment discontinuation due to adverse events was low across all groups:
- Mazdutide 4mg: 1.5%
- Mazdutide 6mg: 0.5%
- Placebo: 1.0%
The low discontinuation rates, particularly for the 6mg dose, suggest good overall tolerability despite gastrointestinal side effects.[3]
Serious Adverse Events
The incidence of serious adverse events was low and comparable to placebo across all treatment groups. No new safety signals were identified beyond those known for the GLP-1 receptor agonist class.[7]
Most GI side effects improve over time as your body adjusts. Tips for management include:
- Eat smaller, more frequent meals
- Avoid high-fat or greasy foods
- Stay well hydrated
- Take medications with food if nausea occurs
- Follow the gradual dose-escalation schedule
Most participants find these side effects diminish significantly after the first few weeks of treatment.
Contact your healthcare provider immediately if you experience:
- Severe or persistent abdominal pain
- Signs of pancreatitis (severe upper stomach pain radiating to back, nausea/vomiting)
- Signs of thyroid tumors (lump in neck, hoarseness, trouble swallowing)
- Severe allergic reactions (rash, difficulty breathing, swelling)
- Vision changes or symptoms of low blood sugar
- Dehydration from persistent vomiting or diarrhea
Path to FDA ApprovalApproval Timeline
While mazdutide received approval in China in mid-2025, the US regulatory pathway is still in earlier stages. Eli Lilly is currently conducting Phase 2 trials in the US population to gather data for eventual FDA submission.[4]
China Approval Provides Proof-of-Concept
The successful NMPA approvals in China for both obesity (June 2025) and type 2 diabetes (September 2025) provide strong clinical validation that may accelerate US development. However, the FDA typically requires trials conducted in diverse patient populations that reflect the US demographic, which is why Eli Lilly is conducting separate Phase 2 trials in the United States.[1]
Innovent Biologics (which holds China rights) prioritized development in the Chinese market and completed Phase 3 trials there first. Eli Lilly (which holds US/global rights) is following a separate development pathway with trials in US populations. This is common when different companies hold regional development rights—each pursues regulatory approval independently in their respective markets.
Current AccessClinical Trials
While Mazdutide awaits FDA approval, you can access it now through clinical trial enrollment:
- Free medication – No cost for Mazdutide or placebo
- Free medical monitoring – Regular check-ups, lab tests, physician visits at no charge
- No insurance required – Trials cover all study-related costs
- Early access – Get Mazdutide before FDA approval
Insurance Coverage OutlookCoverage Outlook
Because mazdutide is not yet FDA-approved in the United States, it is not currently covered by any US insurance plans. However, we can make informed predictions about future coverage based on the approval pathway for similar medications.[8]
Expected Coverage After US FDA Approval
- For Type 2 Diabetes: Likely covered with prior authorization, similar to other GLP-1 medications
- For Obesity: Coverage varies widely by plan; larger employers more likely to cover
- Expected Requirements: BMI thresholds (≥30 or ≥27 with comorbidities), documented lifestyle interventions, prior authorization
- For Type 2 Diabetes: Likely covered on formulary tiers 3-5 (specialty tier)
- For Obesity Only: Not covered—Medicare Part D explicitly excludes weight loss drugs unless also approved for diabetes or other conditions
- Expected Out-of-Pocket: $500-$1,000+ per month for specialty tier medications
- Coverage policies vary significantly by state
- Some states may cover for diabetes; fewer cover for obesity
- Prior authorization and step therapy typically required
Factors That May Improve Coverage
- Dual Indication Approval: If FDA approves for both obesity and diabetes simultaneously (like tirzepatide), coverage rates may be higher
- Cardiovascular Outcomes Data: If future trials demonstrate CV risk reduction, insurers may view it more favorably
- Competitive Pricing: If priced competitively with semaglutide or tirzepatide, broader formulary access is likely
- Manufacturer Savings Programs: Eli Lilly typically offers copay cards and patient assistance programs
It depends on your specific plan and the indication (diabetes vs obesity). Most commercial plans cover GLP-1 medications for diabetes with prior authorization. For obesity, coverage is less consistent—about 40-50% of commercial plans cover obesity medications, while by law basic Medicare Part D coverage excludes drugs used for weight loss.
Check your plan's formulary or contact your insurer to understand their policies for similar medications like Wegovy, Zepbound, or Mounjaro.
FAQs
Mazdutide is currently in Phase 2 trials in the US. Based on typical drug development timelines, FDA approval is estimated for 2028-2029 if trials are successful. However, you may be able to access mazdutide sooner through clinical trial enrollment. Eli Lilly is actively recruiting participants for Phase 2 studies (NCT06143956).
Yes! Eli Lilly is currently conducting Phase 2 trials in the US for mazdutide in patients with obesity. Clinical trial participation provides:
- Free medication (mazdutide or placebo)
- Free medical monitoring and lab tests
- No insurance required
- Early access before FDA approval
Search ClinicalTrials.gov for "mazdutide" or "LY3305677" to find enrolling trials near you.
Mazdutide is a once-weekly subcutaneous injection (similar to Ozempic, Wegovy, or Zepbound). It is not available as an oral medication. The injection is self-administered using a pre-filled pen device.
Both mazdutide and tirzepatide are dual agonist medications, but they target different receptor combinations:
- Mazdutide: GLP-1 + glucagon receptor agonist
- Tirzepatide: GLP-1 + GIP receptor agonist
Tirzepatide has demonstrated up to 21% weight loss in Phase 3 trials. Mazdutide's GLORY-1 trial showed 14.8% weight loss at 48 weeks. However, direct head-to-head comparisons have not been conducted, and mazdutide's glucagon pathway may offer unique benefits for energy expenditure and liver fat reduction.
The key difference is mazdutide's dual mechanism. Semaglutide only activates the GLP-1 receptor, while mazdutide activates both GLP-1 and glucagon receptors. The additional glucagon activation may provide:
- Increased energy expenditure (higher metabolic rate)
- Enhanced fat burning
- Better improvement in liver fat content
- More favorable effects on visceral (abdominal) fat
Both medications show strong efficacy—semaglutide achieves ~15% weight loss, while mazdutide demonstrated 14.8% in Phase 3 trials.
In China, mazdutide is marketed as Xinermei® by Innovent Biologics. In the United States, Eli Lilly has not yet announced a brand name, as the drug is still in Phase 2 development. The brand name will be revealed closer to FDA approval, likely around the time of regulatory filing.
US pricing has not been announced, as mazdutide is not yet FDA-approved. However, based on similar GLP-1 and dual agonist medications, we can expect:
- List Price: $900-$1,400 per month
- With Insurance: $25-$300+ per month (depending on coverage and copay)
- Manufacturer Savings Program: Eli Lilly typically offers copay cards reducing costs to $25-$50/month for commercially insured patients
Actual pricing will depend on FDA approval indication, competition, and insurance formulary placement.
References
- Innovent Biologics. Mazdutide, First Dual GCG/GLP-1 Receptor Agonist, Received Approval from China's NMPA for Chronic Weight Management. PR Newswire. June 27, 2025. https://www.prnewswire.com/news-releases/innovent-announces-mazdutide-first-dual-gcgglp-1-receptor-agonist-received-approval-from-chinas-nmpa-for-chronic-weight-management-302493152.html
- Cheng Z, Chen J, Zhang B, et al. Mazdutide, a dual agonist targeting GLP-1R and GCGR, mitigates diabetes-associated cognitive dysfunction: mechanistic insights from multi-omics analysis. eBioMedicine. 2025;111:105479. doi:10.1016/j.ebiom.2025.105479. PMID: 40479843.
- Ji L, Jiang H, Bi Y, et al. Once-Weekly Mazdutide in Chinese Adults with Obesity or Overweight. N Engl J Med. 2025;392(4):301-312. doi:10.1056/NEJMoa2411528. PMID: 40421736.
- Eli Lilly and Company. A Master Protocol Study of LY3305677 (Mazdutide) in Participants With Overweight or Obesity. ClinicalTrials.gov Identifier: NCT06143956. Updated November 30, 2023. https://clinicaltrials.gov/study/NCT06143956
- Ji L, Gao L, Jiang H, et al. Safety and efficacy of a GLP-1 and glucagon receptor dual agonist mazdutide (IBI362) 9 mg and 10 mg in Chinese adults with overweight or obesity: A randomised, placebo-controlled, multiple-ascending-dose phase 1b trial. EClinicalMedicine. 2022;54:101727. doi:10.1016/j.eclinm.2022.101727. PMID: 36247927.
- Zhang B, Cheng Z, Chen J, et al. Efficacy and Safety of Mazdutide in Chinese Patients With Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial. Diabetes Care. 2024;47(2):220-228. doi:10.2337/dc23-1416. PMID: 37943529.
- Ji L, Jiang H, Cheng Z, et al. A phase 2 randomised controlled trial of mazdutide in Chinese overweight adults or adults with obesity. Nat Commun. 2023;14(1):8042. doi:10.1038/s41467-023-44067-4. PMID: 38092790.
- American Diabetes Association. Standards of Care in Diabetes—2025. Diabetes Care. 2025;48(Suppl 1):S1-S321. https://diabetesjournals.org/care/issue/48/Supplement_1
Disclaimer
The information on this page is for educational and informational purposes only and is not intended as medical advice. Honest Care does not provide medical diagnosis, treatment, or individualized recommendations. Always seek the advice of your physician or other qualified healthcare professional regarding any medical condition or treatment.
While this content has been reviewed for accuracy and balance, new evidence may emerge after publication. Drug availability, indications, and insurance coverage can change over time. Honest Care makes no warranties as to completeness or currentness of the information and is not responsible for decisions made based on this content.