What is Mazdutide?
Mazdutide (IBI362, also known as LY3305677 from its co-development phase with Eli Lilly) is a long-acting dual GLP-1/glucagon agonist developed by Innovent Biologics (China). In 2025, it became the first GLP-1/glucagon dual agonist to receive regulatory approval, cleared by China’s National Medical Products Administration (NMPA) for the treatment of obesity in adults.
What distinguishes mazdutide from semaglutide or tirzepatide is the deliberate incorporation of glucagon receptor agonism. While GLP-1 acts primarily on caloric intake (appetite reduction), glucagon adds a second axis of action: increased energy expenditure. The result is a molecule that addresses obesity from two simultaneous metabolic fronts.
Mechanism of Action
Mazdutide is an acylated peptide that activates two class B receptors with comparable kinetics:
-
GLP-1 receptor (GLP-1R): Stimulates glucose-dependent insulin secretion, suppresses fasting glucagon, reduces appetite via hypothalamic signaling, and slows gastric emptying. This component is responsible for glycemic control and part of the caloric-intake-driven weight reduction.
-
Glucagon receptor (GCGR): Increases hepatic energy expenditure by activating fatty acid oxidation and mild ketogenesis. Promotes thermogenesis in brown adipose tissue and stimulates lipolysis in white adipose tissue. This axis is the key differentiator over pure GLP-1 agonists: it adds active weight loss by “burning more” on top of “eating less.”
Why doesn’t blood glucose rise? The classic concern with glucagon receptor agonism is hyperglycemia (glucagon is the primary counter-regulatory hormone to insulin). Mazdutide resolves this tension because the GLP-1 component provides sufficient insulinotropic stimulus to counteract glucagon’s hyperglycemic effect, resulting in a neutral or mildly favorable glycemic balance, even in type 2 diabetes.
Clinical Results
GLORY Trial — Obesity (JAMA Internal Medicine, 2023)
48-week Phase 3 trial in 332 Chinese adults with BMI ≥28 kg/m² without diabetes:
- Mazdutide 3.0 mg/week: weight loss of 11.3% of body weight.
- Mazdutide 4.5 mg/week: weight loss of 14.0%.
- Placebo: weight loss of 2.5%.
Type 2 Diabetes (Lancet Diabetes & Endocrinology, 2023)
- HbA1c reduction of up to 1.7% in T2D patients.
- 51–64% of participants reached HbA1c targets of <7%.
- Concomitant weight loss of 7–9%.
These results position mazdutide as a competitive alternative to semaglutide, with a differential advantage in the weight loss efficacy profile.
Dose Escalation (Research-Reported Protocols)
Standard Protocol (10 mg vial / BAC 3.0 mL → 3.33 mg/mL)
| Weeks | Weekly Dose | Volume | U-100 Units |
|---|---|---|---|
| 1–4 | 2.5 mg | 0.75 mL | 75 U |
| 5+ | 5.0 mg | 1.50 mL | 150 U |
Note: The 5.0 mg dose (150 U) exceeds a standard 1 mL syringe. A 3 mL syringe is required, or split the dose into two injections at different sites.
Advanced Protocol (10 mg vial / BAC 2.0 mL → 5.0 mg/mL)
| Weeks | Weekly Dose | Volume | U-100 Units |
|---|---|---|---|
| 1–4 | 5.0 mg | 1.00 mL | 100 U |
| 5–8 | 7.5 mg | 1.50 mL | 150 U |
| 9+ | 10.0 mg | 2.00 mL | 200 U |
Note: All doses in the advanced protocol require a 3 mL syringe or multiple injections. This protocol exceeds doses evaluated in approved Phase 3 trials.
Storage and Reconstitution
- Lyophilized (powder): -20 °C, protected from light.
- Reconstituted with BAC water: 2–8 °C (refrigerated), maximum 28 days.
- Standard concentration: 3.33 mg/mL (BAC 3.0 mL) | High dose: 5.0 mg/mL (BAC 2.0 mL).
- Do not shake; gently invert until fully dissolved.
Adverse Effects
The adverse effect profile is consistent with the GLP-1 agonist class:
- Gastrointestinal (most frequent): nausea, vomiting, diarrhea, constipation — primarily at initiation and at dose escalation steps.
- Injection site reactions: localized erythema, induration, pruritus.
- Decreased appetite: desired as a therapeutic effect but may lead to insufficient caloric intake without proper monitoring.
- GI effects generally attenuate after reaching the stable dose.
Long-term cardiovascular safety data outside China are still being evaluated in additional trials; no cardiovascular outcome data equivalent to the SELECT trial (semaglutide) are currently available for mazdutide.
Regulatory Status
- China (NMPA): Approved in 2025 for obesity in adults.
- FDA (United States): Investigational. No NDA or BLA filed as of this date.
- EMA (Europe): Investigational. No MAA filed.
The regulatory pathway in Western markets will depend on whether Innovent Biologics or Eli Lilly (original co-developer) elect to initiate regulatory programs in the U.S. and Europe with their own data.
Mandatory legal disclaimer: This content is for educational and informational purposes only. Mazdutide is not approved by the FDA or EMA for use in humans outside China. This material does not constitute medical advice, does not diagnose conditions, and does not recommend treatments. It should not be used to make medical decisions. Always consult a licensed physician before starting any peptide protocol or modifying your current treatment. Research use only.
Reported protocol (research reference)
| Vial sizes | 10 mg |
|---|---|
| Reported dose | Standard protocol (vial 3.33 mg/mL): Wks 1-4: 2.5 mg | Wks 5+: 5.0 mg (weekly, SubQ). Advanced protocol (vial 5.0 mg/mL): Wks 1-4: 5 mg | Wks 5-8: 7.5 mg | Wks 9+: 10 mg. Under medical supervision only. |
| Half-life | Approximately 7 days — supports weekly dosing. |
| FDA status | Investigational |