WHAT IS MAZDUTIDE

Mazdutide (IBI362) is a synthetic analog of the naturally occurring gut hormone Oxyntomodulin (OXM).  It is a long-acting dual agonist developed for chronic weight management and Type 2 Diabetes. Mazdutide is an innovative, long-acting dual agonist targeting the GLP-1 Receptor (GLP-1R) and the Glucagon Receptor (GCGR).  It is the first drug of its class to receive initial regulatory approval for chronic weight management and Type 2 Diabetes. 

WHAT DOES MAZDUTIDE DO?

Mazdutide is a dual glucagon-like peptide 1 receptor agonist (GLP-1RA) and glucagon receptor agonist, the first in its class. This dual effect appears promising, but more clinical trials are needed.

Mazdutide's dual mechanism synergistically combines the glucose-lowering and appetite-suppressing effects of the GLP-1 pathway with the energy-expending effects of the Glucagon pathway.

Dual Action Pathways

• GLP-1R Activation (Anabolic and Satiety):

  • Enhances glucose-dependent insulin secretion, which improves glucose control.

  • Suppresses glucagon production during hyperglycemia.

  • Slows gastric emptying and promotes satiety via the hypothalamus, helping to regulate appetite.

• GCGR Activation (Catabolic and Energy):

  • Glucagon agonism stimulates the liver to increase energy expenditure (thermogenesis).

  • Promotes hepatic lipolysis (breakdown of fat in the liver), which is highly effective at reducing visceral and hepatic fat.

Metabolic Balance

By combining these two pathways, Mazdutide regulates appetite, metabolism, and improves glucose control. The strong anti-hyperglycemic effects of the GLP-1 pathway counteract the typical blood glucose-raising effects of Glucagon agonism, resulting in a net benefit for potent weight loss and improved metabolic markers.

BENEFITS/ CLINICAL TRIALS 

Mazdutide has demonstrated exceptional efficacy in Chinese Phase 3 trials, positioning it as a significant challenger to established incretin therapies. It is currently undergoing Phase 3 clinical trials globally to assess its effectiveness.

Key Efficacy Findings (Weight Loss and Glycemic Control) 

Mazdutide demonstrates superior efficacy in reducing body weight and improving metabolic health, particularly at higher dosages.

• Superior Weight Loss:

  • A Phase 2 study reported a mean percent change in body weight from baseline of -15.4 percent after 24 weeks with 9 mg Mazdutide, with a reported treatment difference of 14.7 kg versus placebo. Nobody in the placebo group lost 5 percent or more of their body weight.

  • In the GLORY 2 trial, Mazdutide 9 mg achieved a mean body weight reduction of up to 20.1 percent at 60 weeks in obese adults without Type 2 Diabetes (T2D). Over 44 percent of participants achieved greater than or equal to 20 percent weight loss.

  • A separate Phase 2 study reported an average 7.21 percent decrease in body weight after 24 weeks. Higher dosages were associated with higher weight loss (6.35 kg on 3 mg, 9.07 kg on 4.5 mg, and 9.85 kg on 6 mg Mazdutide).

• Improved Glycemic Control: In head to head trials (DREAMS 3), Mazdutide showed superiority to Semaglutide in a composite endpoint of HbA1c reduction and weight loss, achieving a mean HbA1c reduction of approximately -2.03 percent.

Cardiometabolic and Liver Benefits

Clinical studies consistently show significant improvements in health markers beyond simple weight loss:

• Improved Cardiometabolic Markers: Body mass index, blood pressure, waist circumference, lipid levels, and insulin sensitivity were all reduced or improved. Serum uric acid and transaminase levels were also lowered.

• Liver Health: Mazdutide demonstrated significant reduction and resolution of MASLD (Metabolic Dysfunction Associated Steatotic Liver Disease) by promoting hepatic fat breakdown, and liver fat content was reduced.

Neuroprotection

• Cognitive Support: Preclinical evidence suggests Mazdutide mitigates diabetes associated cognitive dysfunction (DACD) better than GLP-1 monotherapy by modulating specific neurotransmission pathways.

Funding and Bias Note 

• Funding: The authors of several reported studies received funding from Innovent Biologics Inc.

Regulatory Status 

• First Approval: Mazdutide has received initial regulatory approval in China's NMPA (National Medical Products Administration) for chronic weight management and T2D.

• US/EU Status: It is currently under Phase 3 investigation globally by Eli Lilly and Innovent Biologics, but is not FDA approved for use in the United States.

SIDE EFFECTS

Mazdutide's side effect profile is consistent with the metabolic hormone agonist class, primarily involving gastrointestinal upset. These effects are generally mild to moderate in severity and typically decrease following proper dose titration.

Common Side Effects

The most common side effects reported in clinical trials include:

• Gastrointestinal (Most Common): Nausea, vomiting, diarrhea, abdominal distension (bloating) or pain, and decreased appetite.

• Metabolic: Hypoglycemia (low blood sugar) is reported, especially in patients with Type 2 Diabetes (T2D).

• Cardiovascular: An increased heart rate (pulse rate) is commonly observed. This is a transient, dose-dependent effect recognized with GLP-1 agonism.

• Other: Upper respiratory tract infection and urinary tract infection.

Less Common and Transient Effects

• Liver Enzymes: Transient elevations in liver enzymes (ALT, AST) were noted in a small number of participants in trials, though these resolved spontaneously.

IS MAZDUTIDE SAFE?

Mazdutide is a recently approved pharmaceutical drug in China for its specified indications, backed by robust Phase 3 clinical trial data in Chinese populations.

Regulatory Status

• China Approval: Mazdutide is a prescription medication approved for use in China, developed through a license agreement between Innovent Biologics and Eli Lilly.

• US/Global Status: It is not currently approved for human use by the FDA in the United States. Its use in other jurisdictions remains restricted to clinical trial settings.

Safety Takeaway

• Tolerability: Mazdutide has a favorable safety and tolerability profile consistent with other GLP-1 therapies, primarily involving transient gastrointestinal side effects.

• Contraindications: As with all incretin therapies, patients with a history of medullary thyroid carcinoma or MEN2 (Multiple Endocrine Neoplasia Type 2) are typically excluded from treatment due to theoretical risks observed in preclinical models of this class of drugs.

DOSAGE

Administration:

• Route: Delivered subcutaneously (SubQ) (under the skin).

• Location: Usually injected into the stomach area.

• Frequency: Administered once a week.

• Half-Life: The prolonged approximately 8 day half-life allows for stable, convenient weekly dosing.

Dosage Guidelines 

Dosage requires gradual dose escalation over several weeks to maximize tolerance and mitigate gastrointestinal side effects.

• Approved Doses (China): The approved doses in China range from 2 mg to 6 mg per week.

• High Dose (Investigational): 9 mg is under review for moderate-to-severe obesity, as clinical trials show this dose achieves the highest efficacy.

RECONSTITUTION

This schedule is designed to mirror clinical trial protocols with gradual titration to improve tolerability. The 3.0 mL dilution provides practical unit measurements for standard maintenance doses.

Reconstitution Steps

1. Draw Diluent: Draw 3.0 mL bacteriostatic water with a sterile syringe.

2. Inject Diluent: Inject the water slowly down the vial wall; avoid foaming.

3. Mix Solution: Do not shake vigorously. Gently swirl the vial until the powder is completely dissolved.

WHERE TO BUY MAZDUTIDE

Researchers should always vet their sources to ensure that a few key factors are present in their test subjects. With the rise in peptide popularity in recent years, many companies have created peptides that undergo little to no testing, quality standards, or regulations. As it is not regulated by the FDA, researchers must do their due diligence and look closely at the company's practices and standards. 

When selecting a supplier for Mazdutide, focus on transparency and quality assurance, not customer testimonials:

1. Quality Documentation: A reputable supplier must provide:
   •  Certificate of Analysis (COA): This document must be recent (corresponding to the batch/lot number purchased) and demonstrate a minimum purity of >95% via High-Performance Liquid Chromatography (HPLC) testing.
   • Mass Spectrometry (MS) Data: The COA must include mass spectrometry (MS) confirmation to verify the compound’s exact molecular weight, confirming its chemical identity.
   • Contaminant Testing: Look for reports on heavy metals, microbial load, and solvent residues (e.g., residual trifluoroacetic acid, or TFA). The presence of these contaminants can severely compromise research and introduce unknown toxicity.
2. Vendor Verification and Transparency 

   • Specialization: Prioritize vendors who specialize in the manufacturing and distribution of peptides for academic and biotechnology research, rather than general supplement vendors.

   • Manufacturing Origin: Inquire about the source of the raw materials and the manufacturing protocols. Ideal suppliers adhere to strict quality control processes.

   • Handling & Storage: The supplier must provide clear documentation on the proper storage and handling procedures for the peptide to maintain its stability and integrity.

Conclusion on Procurement: Given the high risk of contamination, mislabeling, and legal ambiguity. The use of Mazdutide outside of this defined research context poses unacceptable, unquantified risks to human health.

REFERENCES

• “Mazdutide.” National Center for Biotechnology Information. PubChem Compound Database, U.S. National Library of Medicine, pubchem.ncbi.nlm.nih.gov/compound/167312357#section=2D-Structure. Accessed 22 Nov. 2025. 
• “What Is Mazdutide?” Drugs.Com, www.drugs.com/medical-answers/what-mazdutide-3573798/#:~:text=upper%20respiratory%20tract%20infection,vomiting. Accessed 22 Nov. 2025. 
• “Mazdutide (5mg Vial) Dosage Protocol.” Peptidedosages.Com, 20 Nov. 2025, peptidedosages.com/single-peptide-dosages/mazdutide-5mg-vial-dosage-protocol/.
• Nalisa, David Lubasi, et al. “Efficacy and Safety of Mazdutide on Weight Loss among Diabetic and Non-Diabetic Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.” Frontiers, Frontiers, 22 Nov. 2025, www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2024.1309118/full.

• PR Newswire (Innovent Biologics). "$\text{Mazdutide}$ $\text{9 mg}$ $\text{Achieves}$ $\text{Up}$ $\text{to}$ $\text{20.1}\%$ $\text{Weight}$ $\text{Loss}$ $\text{in}$ $\text{Chinese}$ $\text{Adults}$ $\text{with}$ $\text{Obesity}$..."

•  BioSpace (Innovent). "$\text{Innovent}'\text{s}$ $\text{Mazdutide}$ $\text{Shows}$ $\text{Superiority}$ in $\text{Glycemic}$ $\text{Control}$ with $\text{Weight}$ $\text{Loss}$ $\text{over}$ $\text{Semaglutide}$ $\text{in}$ a $\text{Head-to-head}$ $\text{Phase }3$ $\text{Clinical}$ $\text{Trial}$..."

• Frontiers in Endocrinology. "Case $\text{Report}$: $\text{Efficacy}$ and $\text{safety}$ of $\text{dose-escalated}$ $\text{Mazdutide}$, a $\text{GLP}-1/\text{GCGR}$ $\text{dual}$ $\text{agonist}$..."

• InvivoChem. "$\text{Mazdutide}$ ($\text{IBI}-362$; $\text{LY}-3305677$; $\text{OXM}-3$)"