Mazdutide

Mazdutide is a synthetic peptide. It is an acylated, long-acting analog of the human hormone oxyntomodulin, designed as a dual agonist that acts on both the glucagon-like peptide-1 receptor (GLP-1R) and the glucagon receptor (GCGR). It acts as a therapeutic agent for obesity and type 2 diabetes by reducing appetite and increasing energy expenditure.

Key Benefits

May support significant weight loss by helping reduce appetite and calorie intake
Commonly researched for improving blood sugar control and metabolic health
May help support healthy fat loss while preserving lean body mass
Research suggests potential benefits for cardiovascular and overall metabolic wellness support

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FDA-Approved Uses

Mazdutide is under active clinical development in the US by Eli Lilly.

China NMPA approvals (Xinermei®)

Obesity / Weight Management (June 2025):

World’s FIRST approved dual GLP-1/glucagon receptor agonist for obesity
Indicated for adults with BMI ≥28 kg/m² or ≥24 kg/m² with weight-related comorbidity
Type 2 Diabetes (September 2025):
Approved as adjunct to diet and exercise for glycemic control in adults with T2DM

US FDA Development Timeline:

Phase 1 (high-dose): Completed 2025 (doses up to 16 mg studied; Diabetes Obes Metab 2025)
Phase 2 (US): Active enrollment (NCT06143956) — ongoing
Phase 3: Expected 2026–2027
NDA/BLA submission: Estimated 2027–2028
FDA decision: Estimated 2028–2029
[If granted Priority Review as first dual GLP-1/GCGR agonist: possible 2027]

Conditions being studied:

Obesity / Overweight (primary US indication under development)
Type 2 Diabetes
Metabolic dysfunction-associated fatty liver disease (MAFLD/MASLD)
Cardiovascular outcomes (planned)

Mechanism distinction vs. existing GLP-1 drugs:

Semaglutide, liraglutide: GLP-1 receptor agonist only
Tirzepatide: GLP-1 + GIP dual agonist
Retatrutide: GLP-1 + GIP + glucagon triple agonist
Mazdutide: GLP-1 + GLUCAGON dual agonist (different pairing from tirzepatide)

WADA status: Not on WADA Prohibited List

Trade Names in USA and Manufacturers

China-approved brand:
– Xinermei® (mazdutide injection) — approved China NMPA June/September 2025
Manufacturers: Innovent Biologics (Suzhou) Co. Ltd. / Innovent Biologics, Inc.
Distributor in China: Eli Lilly and Company (partnership)

Developers:
– Originally developed by: Innovent Biologics (Suzhou) Co. Ltd. (China)
– Co-developed/licensed: Eli Lilly and Company (Indianapolis, IN, USA)
– Compound codes: IBI362 (Innovent) / LY3305677 (Eli Lilly)

US availability (as of May 2026):
– Phase 2 clinical trial (NCT06143956): Only legal supervised US access
– Importation of Xinermei® from China: Legally complex; not recommended without medical supervision
– Not available via US pharmacies, compounding, or telehealth for general use

Molecular identity:
– Long-acting GLP-1 and glucagon receptor (GCGR) dual agonist peptide
– Administered as once-weekly subcutaneous injection
– Fatty acid chain modification enables long half-life (~7 days) for weekly dosing
– Exact full sequence not publicly disclosed in available literature

Dosage

China-approved dosing (Xinermei®):
Once-weekly subcutaneous injection with dose escalation:

Obesity indication:
Weeks 1–4: 1 mg/week
Weeks 5–8: 2 mg/week
Weeks 9–12: 3 mg/week
Week 13+: 4–6 mg/week (maintenance; max studied: 6 mg for obesity)

Type 2 Diabetes indication:
Similar escalation schedule; doses per physician judgment

US Phase 1 trial doses (research only — NOT approved):
Up to 16 mg/week studied (Diabetes Obes Metab, 2025 publication)

US Phase 2 trial doses (NCT06143956 — investigational):
Multiple doses under evaluation; results pending

Route: Subcutaneous injection, abdomen, thigh, or upper arm
Frequency: Once weekly (consistent with semaglutide and tirzepatide dosing schedules)
No dose adjustment required for mild-to-moderate renal impairment (based on dual GLP-1/GCGR profile)

Pricing

China pricing (Xinermei® — where approved):
Estimated: ~$200–$400/month (based on NMPA pricing and market reports)
[Exact China retail price varies by province and insurance coverage]

US cost to patients:
– Phase 2 trial (NCT06143956): Free to enrolled participants
– No other legal US access pathway as of May 2026

Projected US commercial pricing (post-FDA approval — speculative):
Expected to be comparable to tirzepatide (Zepbound/Mounjaro) given Eli Lilly’s existing GLP-1 pricing structure
Likely: $1,000–$1,400/month list price (estimated; not confirmed)
With insurance + savings programs: Potentially as low as $25–$99/month for eligible commercially insured patients

Tips

Monitor Eli Lilly’s Phase 3 trial initiation (expected 2026–2027) and NDA submission (estimated 2027–2028). FDA priority review designation as the first dual GLP-1/GCGR agonist could accelerate the timeline to 2027.
Mazdutide’s key differentiator from tirzepatide is the glucagon receptor component (vs. tirzepatide’s GIP component). Glucagon receptor activation increases energy expenditure and thermogenesis ; a different additional mechanism from GIP’s insulin-sensitizing effects.
Patients in China with access to Xinermei® have the only current legitimate pharmaceutical access. Importation for personal use in the US is legally complex and not generally recommended.
For US patients: The only supervised, legitimate US access is via clinical trial enrollment. Search ClinicalTrials.gov for ‘mazdutide’ or ‘LY3305677’ or ‘NCT06143956’.
Side effect profile is consistent with the GLP-1 drug class (nausea, vomiting, GI effects) ; similar management strategies apply (slow dose escalation, eating habits, antiemetics if needed).

Side Effects

From Phase 1, Phase 2, and Phase 3 GLORY-1 clinical trial data:

Consistent with GLP-1 drug class profile:
– Nausea: Most commonly reported; dose-dependent; typically improves with dose escalation period
– Vomiting: Less common than nausea; also dose-dependent
– Mild gastrointestinal discomfort / abdominal pain
– Constipation or diarrhea
– Decreased appetite (therapeutically desired effect; sometimes excessive)

General tolerability assessment:
– Phase 2 (Nature Communications, 2023): ‘Well tolerated over 24 weeks; no serious safety signals’
– Phase 1 high-dose trial (Diabetes Obes Metab, 2025): Up to 16 mg/week studied; ‘generally consistent with other GLP-1–based drugs’
– GLORY-1 Phase 3: 4 mg and 6 mg doses for 32 weeks in Chinese adults — adverse events consistent with GLP-1 class; no unexpected safety signals published

Glucocagon component-specific considerations:
– Glucagon receptor activation raises blood glucose (opposing GLP-1’s insulin-stimulating effect) — net effect in clinical trials is favorable glycemic control, but transient hyperglycemia is possible in some patients
– No hypoglycemia excess vs. GLP-1 monotherapy (glucose-dependent mechanisms)

⚠️ Long-term safety data (beyond 32–68 weeks) not yet available — Phase 3 trials ongoing

Contraindications

No formal FDA contraindications (no approved US label).
Based on Phase 2/3 trial exclusion criteria and GLP-1 class pharmacology:

– Personal or family history of medullary thyroid carcinoma (MTC): Expected class contraindication (GLP-1R activation → thyroid C-cell concern; shared with semaglutide, tirzepatide)
– Multiple endocrine neoplasia syndrome type 2 (MEN 2): Expected contraindication
– History of pancreatitis: Excluded from clinical trials
– Severe renal or hepatic impairment: Not fully characterized; excluded from key trials
– Pregnancy: Expected contraindication (GLP-1 class effect)
– Type 1 diabetes: Not studied; expected exclusion
– Hypersensitivity to mazdutide or components

⚠️ Final contraindications to be established in FDA-approved prescribing information if/when approved.

Pharmacology

Mazdutide (IBI362 / LY3305677) is a synthetic, long-acting peptide dual agonist of two receptors: the glucagon-like peptide-1 receptor (GLP-1R) and the glucagon receptor (GCGR). It was developed by Innovent Biologics (China) in collaboration with Eli Lilly and Company.

Key pharmacological distinction:
– GLP-1R + GIP receptor (tirzepatide, retatrutide): This pairing leverages insulin secretion enhancement (GIP) + appetite suppression (GLP-1)
– GLP-1R + GCGR (mazdutide): This pairing leverages energy expenditure increase (glucagon) + appetite suppression (GLP-1) — a different complementary mechanism

Half-life enabling once-weekly dosing:
Engineered with fatty acid chain modification enabling albumin binding and extended half-life of approximately 7 days — same strategy as semaglutide (Ozempic/Wegovy).

FDA status: No approved drug; Phase 2 active in US; Phase 3 expected 2026–2027.

Approvals outside US:
– China NMPA: Obesity (June 2025) and T2DM (September 2025) under brand Xinermei®
– World’s FIRST approved dual GLP-1/glucagon receptor agonist for obesity

Mechanism of action

GLP-1 Receptor Activation (shared mechanism with semaglutide):
→ Glucose-dependent insulin secretion from pancreatic beta cells
→ Glucagon suppression from alpha cells
→ Slowed gastric emptying
→ Hypothalamic appetite suppression (reduced caloric intake)
→ Weight loss primarily via reduced food intake

Glucocagon Receptor (GCGR) Activation (unique addition vs. semaglutide):
→ Increases hepatic glucose output (acutely; balanced by GLP-1’s insulin effect)
→ Increases energy expenditure via thermogenesis (brown adipose tissue activation)
→ Promotes lipolysis in fat tissue (direct fat-burning effect)
→ Reduces liver fat (hepatic lipid metabolism improvement — basis for MAFLD indication)
Net metabolic effect: Greater energy expenditure + fat oxidation on top of GLP-1’s appetite suppression → enhanced weight loss vs. GLP-1 alone

Dual agonism balance:
The opposing glucose effects (GLP-1 lowers, GCGR raises) are carefully balanced in the designed molecule to produce favorable glycemic control overall, while the weight-loss effects are additive (both pathways reduce body weight through different mechanisms).

Result Claims By Different Companies

Innovent Biologics / Eli Lilly (based on published clinical trial data):

Phase 2 (Nature Communications, 2023 — Chinese adults):
– Doses: 3 mg, 4.5 mg, 6 mg vs. placebo; 24 weeks
– Body weight reductions: Statistically significant at all doses vs. placebo
– Well-tolerated; no serious safety signals
– Primary endpoint (% body weight change at week 24) met

Phase 1 high-dose trial (Diabetes Obes Metab, Aug 2025 — Eli Lilly-led, US-based):
– Doses up to 16 mg/week tested
– Statistically significant weight reductions vs. placebo
– Safety profile consistent with GLP-1 drug class
– Published by Melissa K. Thomas et al. (Eli Lilly)

Phase 3 GLORY-1 (NEJM publication):
– 4 mg or 6 mg once-weekly for 32 weeks in Chinese adults with overweight/obesity
– ‘Clinically relevant reductions in body weight’ vs. placebo
– NMPA approval for obesity based on this and supporting data

⚠️ US Phase 3 data pending. All efficacy data from Chinese populations. Cross-population generalizability to Western populations requires confirmation in ongoing/planned US Phase 3 trials. FDA will require US or global trial data for NDA approval.

Disclaimer

This content about “Mazdutide (IBI362 / LY3305677) Dual GLP-1 / Glucagon Receptor Agonist” is for informational and educational purposes only, is not medical advice, does not replace consultation with a licensed healthcare professional, and affiliate links may result in compensation at no additional cost to you.