Mazdutide

Mazdutide is a next-generation dual GLP-1/glucagon receptor agonist that has emerged as one of the most promising peptides for weight management and metabolic health. Developed as an analog of oxyntomodulin, this compound simultaneously activates both the glucagon-like peptide-1 receptor (GLP-1R) and the glucagon receptor (GCGR), producing superior weight loss outcomes compared to single-receptor agonists like semaglutide. It has gained significant popularity among individuals seeking effective solutions for obesity, type 2 diabetes management, and metabolic syndrome. Clinical trials have demonstrated weight reductions of 10-18% over treatment periods of 24-48 weeks, with typical maintenance doses ranging from 4mg to 9mg administered once weekly via subcutaneous injection.

What Is Mazdutide?

Mazdutide (also known as IBI362 or LY3305677) is a synthetic peptide analog of oxyntomodulin, a naturally occurring gut hormone released after eating. It functions as a dual agonist, meaning it activates two distinct receptors: the GLP-1 receptor and the glucagon receptor. This dual mechanism distinguishes it from single-target GLP-1 receptor agonists like semaglutide and liraglutide.

What makes mazdutide unique is its balanced activation of both receptor pathways. While GLP-1 receptor activation promotes insulin secretion, reduces appetite, and slows gastric emptying, glucagon receptor activation increases energy expenditure and improves hepatic fat metabolism. This combination produces more comprehensive metabolic benefits than either pathway alone.

The primary human-use benefits include:

• Significant body weight reduction (10-18% in clinical trials)
• Improved glycemic control and HbA1c reduction
• Enhanced hepatic fat metabolism and liver health
• Reduced waist circumference
• Improved cardiovascular risk markers
• Potential neuroprotective effects

How It Works

GLP-1 Receptor Activation

When mazdutide binds to GLP-1 receptors, it triggers several metabolic responses. In the pancreas, it enhances glucose-dependent insulin secretion from beta cells, meaning insulin is released only when blood glucose is elevated. This mechanism reduces the risk of hypoglycemia compared to traditional insulin-stimulating medications.

GLP-1 receptor activation also acts on the central nervous system to suppress appetite and increase satiety. Additionally, it delays gastric emptying, which prolongs the feeling of fullness after meals and reduces overall caloric intake.

Glucagon Receptor Activation

The glucagon receptor component provides benefits that GLP-1 agonists alone cannot achieve. GCGR activation stimulates hepatic glucose production and, more importantly, increases energy expenditure through enhanced thermogenesis. This means the body burns more calories at rest, contributing to greater weight loss.

Furthermore, glucagon receptor activation improves hepatic lipid metabolism, helping to reduce liver fat accumulation—a significant benefit for individuals with non-alcoholic fatty liver disease (NAFLD), which commonly accompanies obesity and type 2 diabetes.

Synergistic Dual Action

The genius of mazdutide lies in how these two pathways complement each other. While glucagon typically raises blood glucose, the concurrent GLP-1 receptor activation counterbalances this effect, maintaining glycemic control while still delivering the metabolic benefits of glucagon signaling. This balanced approach allows for superior weight loss without compromising blood sugar management.

Neuroprotective Mechanisms

Emerging research suggests mazdutide may offer cognitive benefits beyond metabolic improvements. Studies in diabetic mouse models have shown that mazdutide improves cognitive function, preserves neuronal structure, and enhances synaptic plasticity through modulation of glutamatergic neurotransmission and reduction of neuroinflammation.

Dosage Protocols

Mazdutide is administered via subcutaneous injection once weekly. Clinical trials have employed a dose-escalation approach to minimize gastrointestinal side effects:

Initiation Phase:

• Week 1-4: 1.5mg once weekly
• Week 5-8: 3mg once weekly

Escalation Phase:

• Week 9-12: 4.5mg once weekly
• Week 13-16: 6mg once weekly (if tolerated)

Maintenance Phase:

• 4mg, 6mg, or 9mg once weekly, depending on individual response and tolerability

Higher doses (up to 16mg) have been studied and shown greater weight loss, though gastrointestinal side effects increase proportionally. The optimal dose should be individualized based on efficacy, tolerability, and treatment goals.

Cycling Considerations:
Unlike some peptides, mazdutide is typically used continuously rather than cycled. Long-term studies spanning 48 weeks have demonstrated sustained efficacy without the need for treatment breaks. However, some users may choose to reduce dosage during maintenance phases once target weight is achieved.

Administration

Mazdutide is administered via subcutaneous injection, typically in the abdomen, thigh, or upper arm. The injection site should be rotated with each dose to prevent lipodystrophy.

Injection Procedure:

1. Allow the medication to reach room temperature if refrigerated
2. Clean the injection site with an alcohol swab
3. Pinch a fold of skin at the injection site
4. Insert the needle at a 45-90 degree angle
5. Inject the medication slowly
6. Remove the needle and apply gentle pressure

Injections should be administered on the same day each week, though the time of day can vary. If a dose is missed, it should be administered as soon as possible within 3 days; otherwise, skip to the next scheduled dose.

Results Timeline

Based on clinical trial data, users can expect the following progression:

Weeks 1-4:

• Initial appetite suppression becomes noticeable
• Mild gastrointestinal effects may occur as the body adjusts
• Weight loss of 1-3% typically observed

Weeks 4-12:

• Significant appetite reduction established
• Weight loss accelerates to 5-8%
• Improvements in fasting glucose and HbA1c begin
• Waist circumference reduction becomes measurable

Weeks 12-24:

• Weight loss reaches 10-14%
• Metabolic markers show substantial improvement
• Liver fat reduction evident in imaging studies
• Gastrointestinal side effects typically diminish

Weeks 24-48:

• Weight loss may reach 15-18% at higher doses
• Metabolic improvements plateau at optimal levels
• Long-term maintenance phase begins
• Cardiovascular risk markers show sustained improvement

Research Evidence

Mazdutide has undergone extensive clinical evaluation. Key findings include:

DREAMS-1 Trial: This Phase 3 study demonstrated that mazdutide monotherapy significantly reduced HbA1c and body weight in Chinese adults with type 2 diabetes. Participants achieved clinically meaningful improvements in both glycemic control (

Head-to-Head Comparison: A direct comparison trial showed mazdutide achieved 10.29% mean weight reduction versus 6.00% for semaglutide, demonstrating superiority of the dual-agonist approach.

Phase 2 Obesity Trial: In adults with overweight or obesity (BMI ≥28), mazdutide at doses up to 6mg produced dose-dependent weight loss, with the highest dose achieving approximately 11.3% reduction over 24 weeks.

Adolescent Study: A Phase 1b trial in Chinese adolescents with obesity demonstrated significant weight loss and metabolic benefits, expanding the potential patient population.

Neuroprotection Research: Preclinical studies have shown mazdutide outperforms single GLP-1 agonists in improving cognitive function in diabetic models, suggesting potential applications beyond metabolic disease.

Stacking

Mazdutide is generally used as a standalone therapy due to its comprehensive dual-receptor mechanism. However, some considerations for combination approaches include:

With Metformin: Clinical trials have evaluated mazdutide both as monotherapy and in combination with metformin. The combination appears safe and may provide additive glycemic benefits for individuals with type 2 diabetes.

Caution with Other GLP-1 Agonists: Combining mazdutide with other GLP-1 receptor agonists (semaglutide, tirzepatide) is not recommended due to overlapping mechanisms and increased risk of gastrointestinal adverse effects.

Lifestyle Integration: Mazdutide works best when combined with caloric restriction and regular physical activity. The appetite-suppressing effects make adherence to dietary modifications easier.

Reconstitution, Storage & Prep

For research-grade mazdutide obtained as lyophilized powder:

Storage (Unreconstituted):

• Store at -20°C for long-term preservation
• Keep in a cool, dry place away from light
• Stable at room temperature for short periods but refrigeration preferred

Reconstitution:

1. Allow the vial to reach room temperature
2. Use bacteriostatic water for reconstitution
3. Add water slowly along the vial wall—do not inject directly onto the powder
4. Gently swirl (do not shake vigorously) until fully dissolved
5. Allow 15-30 minutes for complete dissolution
6. Solution should be clear; discard if cloudy or contains particles

Storage (Reconstituted):

• Store at 2-8°C (refrigerator)
• Use within 28-30 days of reconstitution
• Aliquot into smaller portions to avoid repeated freeze-thaw cycles
• Protect from light

Side Effects

The most common adverse effects are gastrointestinal in nature and typically diminish with continued use:

Common (>10% incidence):

• Nausea (23-50%)
• Diarrhea (29-36%)
• Decreased appetite (29%)
• Vomiting (14-25%)

Less Common:

• Abdominal distension/bloating
• Upper respiratory tract infection
• Urinary tract infection
• Hypoglycemia (primarily in diabetic patients, ~10%)
• Injection site reactions

Management Strategies:

• Start at lower doses and escalate gradually
• Take with food if nausea occurs
• Stay well-hydrated
• Eat smaller, more frequent meals
• Avoid high-fat foods that may exacerbate GI symptoms

Most gastrointestinal effects are transient and mild-to-moderate in severity. Discontinuation rates due to adverse events in clinical trials were comparable to placebo groups.

Legal Status / FDA

China: Mazdutide received approval from China's National Medical Products Administration (NMPA) in June 2025 for chronic weight management, making it the world's first approved dual GCG/GLP-1 receptor agonist for this indication.

United States: Mazdutide is currently in Phase 2 clinical development in the US. FDA approval is not expected until 2028-2029, pending completion of Phase 3 trials.

Europe and Other Regions: Regulatory submissions are anticipated following completion of global clinical trials.

Research Chemical Status: In jurisdictions where mazdutide is not approved, it may be available as a research chemical for investigational purposes only.

Sports/WADA

GLP-1 receptor agonists as a class are not currently listed on the World Anti-Doping Agency (WADA) Prohibited List. However, athletes should note:

• WADA's Prohibited List is updated annually
• The metabolic and weight-altering effects of mazdutide could theoretically provide competitive advantages in weight-class sports
• Athletes should verify current status with their sport's governing body before use
• Some sports organizations may have additional restrictions beyond WADA guidelines

The 2025 Prohibited List came into effect January 1, 2025, and athletes should consult GlobalDRO.com or their national anti-doping organization for the most current guidance.

Conclusion

Mazdutide represents a significant advancement in peptide therapeutics for metabolic health. Its dual GLP-1/glucagon receptor mechanism delivers superior weight loss compared to single-target agonists while maintaining excellent glycemic control. Clinical evidence demonstrates weight reductions of 10-18%, improved liver health, and potential neuroprotective benefits. While gastrointestinal side effects are common initially, they typically resolve with continued use and proper dose escalation. As the first approved dual-receptor agonist of its kind, mazdutide offers a promising option for individuals seeking comprehensive metabolic support beyond what traditional GLP-1 agonists provide.

FAQ

How does mazdutide compare to semaglutide?
Head-to-head trials show mazdutide achieves approximately 10.29% weight loss compared to 6.00% with semaglutide, representing a significant advantage due to its dual-receptor mechanism that increases energy expenditure in addition to reducing appetite.

How often is mazdutide injected?
Mazdutide is administered once weekly via subcutaneous injection. The injection can be given at any time of day, with or without food, on the same day each week.

What is the typical starting dose?
Most protocols begin at 1.5mg weekly, escalating every 4 weeks through 3mg and 4.5mg before reaching maintenance doses of 4-9mg depending on individual response and tolerability.

How long until I see results?
Appetite suppression typically begins within the first week. Measurable weight loss (3-5%) usually occurs within 4-8 weeks, with maximum effects (10-18%) achieved over 24-48 weeks of treatment.

Can mazdutide be used for type 2 diabetes?
Yes, mazdutide has demonstrated significant HbA1c reductions in clinical trials and is approved in China for both weight management and type 2 diabetes treatment.

Is mazdutide safe for long-term use?
Clinical trials up to 48 weeks have shown a favorable safety profile with no unexpected adverse events. The most common side effects are gastrointestinal and typically diminish over time.

Does mazdutide require refrigeration?
Unreconstituted powder should be stored at -20°C for long-term stability. Once reconstituted, it should be refrigerated at 2-8°C and used within 28-30 days.

Can I use mazdutide if I'm not diabetic?
Yes, mazdutide has been studied and approved specifically for weight management in individuals with overweight or obesity, regardless of diabetes status.

References:

1. Ji L, et al. A phase 2 randomised controlled trial of mazdutide in Chinese overweight adults or adults with obesity. Nature Communications. 2023;14:8289. https://www.nature.com/articles/s41467-023-44067-4
2. Dong W, et al. Mazdutide, a dual agonist targeting GLP-1R and GCGR, mitigates diabetes-associated cognitive dysfunction. eBioMedicine. 2025;117:105791. https://pmc.ncbi.nlm.nih.gov/articles/PMC12205698/
3. Mazdutide versus placebo in Chinese adults with type 2 diabetes. Nature. 2025. https://www.nature.com/articles/s41586-025-10026-w
4. Mazdutide reduces body weight in adults with overweight or obesity. Diabetes, Obesity and Metabolism. 2025. https://dom-pubs.onlinelibrary.wiley.com/doi/full/10.1111/dom.70040
5. Safety and efficacy of a GLP-1 and glucagon receptor dual-agonist mazdutide. eClinicalMedicine. 2022. https://www.sciencedirect.com/science/article/pii/S2589537022004217
6. Efficacy and safety of Mazdutide on weight loss among Chinese adults with overweight or obesity. Frontiers in Endocrinology. 2024. https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2024.1309118/full
7. Efficacy and Safety of Mazdutide in Chinese Patients with Type 2 Diabetes. PMC. 2023. https://pmc.ncbi.nlm.nih.gov/articles/PMC10733643/
8. Innovent Announces Mazdutide Approval from China's NMPA. PR Newswire. 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
9. Mazdutide shows superiority to semaglutide in head-to-head trial. Drug Discovery World. 2025. https://www.ddw-online.com/mazdutide-shows-superiority-to-semaglutide-in-a-head-to-head-trial-38374-202510/
10. WADA 2025 Prohibited List. World Anti-Doping Agency. 2024. https://www.wada-ama.org/sites/default/files/2024-09/2025list_en_final_clean_12_september_2024.pdf
11. What is mazdutide? Drugs.com. https://www.drugs.com/medical-answers/what-mazdutide-3573798/
12. Mazdutide - Wikipedia. https://en.wikipedia.org/wiki/Mazdutide