Library / Peptides / Weight Management / Mazdutide
Emerging evidence · Grade B

Mazdutide

Mazdutide (LY3305677 / IBI362)
Score
76 / 100
Cadence
Once weekly
Class
GLP-1 / glucagon
Status
Approved in China
TL;DR
01
A once-weekly GLP-1 and glucagon receptor dual agonist (IBI362 / LY3305677) from Innovent Biologics, partnered with Eli Lilly — the glucagon arm is meant to add energy expenditure on top of appetite suppression.
02
In the phase 3 GLORY-1 trial in China, mazdutide 6 mg produced about 14% weight loss at 48 weeks, with roughly half of participants losing at least 15%.
03
It is approved in China for weight management, but is investigational everywhere else — there is no FDA or EMA approval and no Western phase 3 trial yet.
04
Side effects are mainly gastrointestinal and mostly mild; discontinuation for adverse events was strikingly low (~0.5–1.5%).
05
The open questions are generalizability beyond a Chinese-only trial population and the long-term cardiovascular and hepatic safety of adding glucagon agonism — no outcomes trial has reported.
Wt loss (GLORY-1, 6 mg)
−14.0%
NEJM 2025 · 48 wk
Wt loss (GLORY-1, 4 mg)
−11.0%
NEJM 2025 · 48 wk
≥15% weight loss (6 mg)
49.5%
GLORY-1 · 48 wk
Phase 2 (6 mg)
−11.3%
Nat Commun 2023 · 24 wk
Discontinued for AEs
0.5–1.5%
GLORY-1 · very low
Part 01 · How it works

Mechanism.

Mazdutide activates two receptors at once. Like semaglutide, it hits the GLP-1 receptor to blunt appetite and improve blood sugar. It also activates the glucagon receptor — the same hormone that raises blood sugar in a fasting state, but which at controlled levels also nudges the body to burn more energy and mobilize fat from the liver. The bet is that pairing the two produces more weight loss than GLP-1 alone; the catch is that glucagon is a double-edged signal, so its long-term effects need watching.

If a GLP-1 drug turns down how much fuel you take in, mazdutide adds a second lever that also turns up how much fuel you burn. Two dials — but the second one is the same hormone your body uses to raise blood sugar, so it has to be tuned carefully.

GLP-1R agonism
Agonist at the GLP-1 receptor — glucose-dependent insulin secretion, delayed gastric emptying, appetite suppression.
Glucagon receptor agonism
Co-agonist at the glucagon receptor, increasing energy expenditure and hepatic lipid mobilization; also the mechanism behind heart-rate and hepatic effects that require monitoring.
Dual-agonist rationale
Combining incretin appetite suppression with glucagon-driven energy expenditure aims for greater weight loss than GLP-1 monotherapy.
Once-weekly dosing
Engineered for a long half-life supporting once-weekly subcutaneous administration.
Part 02 · Dosing & administration

How it's taken.

Clinical · trial-validated

Values below describe how Mazdutide has been administered in human clinical trials and/or approved labeling. Provided for educational purposes only — this is not medical advice and not instructions for self-administration. Consult your healthcare provider before making any health decision.

Titration
→ 4 mg or 6 mg
GLORY-1 escalated over several weeks to the assigned maintenance dose.
TARGET
Maintenance
4–6 mg
Once-weekly subcutaneous; 6 mg gave the larger weight loss.
·
Doses below are values from published trials and Chinese labeling, not instructions. Mazdutide is not approved outside China.
·
Trials titrate upward over several weeks to limit gastrointestinal effects.
·
Studied cadence is once weekly by subcutaneous injection.
Need help with reconstitution?

Use the free peptide calculator for dilution, unit conversion, and injection volume.

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Part 03 · Safety

Side effects, rare serious events, who shouldn't.

Common
Diarrhea
Among the most frequent events across phase 1b–3; mostly mild-to-moderate.
Common
Nausea
Typical incretin GI effect; peaks during escalation.
Common
Decreased appetite
Expected on-mechanism effect.
Common
Vomiting / abdominal distension
Reported among GI events; generally mild.
Common
Upper respiratory / urinary tract infection
Noted in early-phase trials; relationship to drug uncertain.
Reported
Serious · rare
Serious adverse events
No serious adverse events in the phase 1b trials; discontinuation for AEs only 0.5–1.5% in GLORY-1.
None in phase 1b
Increased heart rate (glucagon effect)
A recognized class consideration for glucagon co-agonism; long-term cardiovascular data pending.
Not quantified in abstracts
Hepatic / transaminase changes
Glucagon agonism affects hepatic glucose and lipid handling; long-term liver safety not yet established.
Not quantified in abstracts
Absolute · do not use
×
Personal or family history of medullary thyroid carcinoma
×
Multiple endocrine neoplasia syndrome type 2 (MEN2)
×
Pregnancy or breastfeeding
×
Children under 18
×
Known hypersensitivity to mazdutide or any component
×
History of pancreatitis
×
Severe gastrointestinal disease (gastroparesis)
Relative · discuss first
!
Pregnancy or breastfeeding — no adequate human data
!
History of pancreatitis — discuss with GI / endocrinology before any incretin-class agent
!
Significant cardiovascular disease — glucagon agonism can raise heart rate; long-term CV safety unproven
!
Hepatic impairment — glucagon receptor activity affects the liver; caution pending long-term data
!
Anyone outside China seeking an approved therapy — mazdutide is investigational elsewhere
Interactions
Insulin
Increased risk of hypoglycemia; dose adjustment of insulin likely required
Major
Sulfonylureas
Additive hypoglycemic effect; dose reduction may be necessary
Major
Oral medications with narrow therapeutic index (warfarin, levothyroxine, oral contraceptives)
GLP-1/glucagon dual agonism delays gastric emptying, potentially altering absorption of oral medications
Moderate
Other GLP-1 receptor agonists
Additive GI and pancreatic effects; should not be combined
Major
Labs to monitor
HbA1c
Baseline and every 3 months
GLP-1/glucagon dual agonist — monitor glycemic control
Fasting Glucose & Insulin
Baseline and monthly
Track glucose homeostasis
Lipase & Amylase
Baseline and every 3 months
Pancreatitis screening (GLP-1 class concern)
CMP (Comprehensive Metabolic Panel)
Baseline and every 3 months
Liver and kidney function
Lipid Panel
Baseline and every 3 months
Glucagon component may affect lipid metabolism
Thyroid Panel (TSH, Free T4)
Baseline and every 6 months
GLP-1 class thyroid C-cell concern
Part 04 · Evidence

How strong is the evidence?

76
Grade B
Grade B. Mazdutide has a positive phase 3 trial (GLORY-1, NEJM) and a national approval — unusually strong for an 'Emerging' rating. It is held there because the entire pivotal evidence base is a single-country (Chinese) population, there is no Western phase 3 or FDA/EMA approval, and no cardiovascular outcomes trial has reported.
Mechanistic plausibility
GLP-1/glucagon co-agonism is biologically coherent; the glucagon arm adds both a rationale and a risk.
82
Human evidence
Phase 3 GLORY-1 plus phase 2 and two phase 1b trials, supporting a China approval — but all in Chinese populations.
80
Safety & tolerability
GI-dominant, very low discontinuation; glucagon effects on heart rate and liver need long-term follow-up.
75
Durability
48-week efficacy data; no long-term maintenance or cardiovascular-outcomes evidence yet.
68
Independence
All pivotal trials Innovent-sponsored and single-country; no independent or non-Chinese replication.
58
Part 05 · Research log

Every study we cite.

We list each study with its methodology, funding source, and our quality grade. Flagged studies aren't dismissed — they're tagged so you can weigh them.

01
2025
New England Journal of Medicine Industry funded
GLORY-1 — once-weekly mazdutide in Chinese adults with obesity or overweight
At 48 weeks, weight change was −11.0% (4 mg) and −14.0% (6 mg) vs +0.3% placebo; 49.5% of the 6 mg group lost ≥15%. Discontinuation for adverse events was 0.5–1.5%.
Phase 3 RCT, 48 wk, double-blind, placebo-controlled · n = 610 · Funded by Innovent; conducted entirely in China, limiting direct generalizability to other populations.
PMID 40421736 ↗
High
02
2023
Nature Communications Industry funded
Phase 2 mazdutide in Chinese overweight adults or adults with obesity
Weight loss −6.7% / −10.4% / −11.3% (3 / 4.5 / 6 mg) vs +1.0% placebo; well tolerated with GI-dominant adverse events.
RCT, 24 wk, double-blind, placebo-controlled (3 / 4.5 / 6 mg) · n = 248 · Funded by Innovent; interim analysis of a two-part phase 2 trial in a Chinese population.
PMID 38092790 ↗
High
03
2022
EClinicalMedicine Industry funded
Phase 1b high-dose mazdutide (9 mg / 10 mg) in Chinese adults with overweight or obesity
−11.7% weight loss at 12 weeks (9 mg cohort) vs −1.8% placebo; all adverse events mild-to-moderate, none serious.
Randomized, placebo-controlled, multiple-ascending-dose phase 1b · n = 24 · Funded by Innovent; n=24 dose-ranging cohort, hypothesis-generating only.
PMID 36247927 ↗
Moderate
04
2022
Nature Communications Industry funded
Phase 1b IBI362 (mazdutide) in Chinese patients with type 2 diabetes
Well tolerated with clinically meaningful reductions in HbA1c and fasting glucose; GI-dominant adverse events comparable to dulaglutide.
Randomized, placebo- and active (dulaglutide)-controlled phase 1b, 12 wk · n = 43 · Funded by Innovent; small early-phase diabetes cohort.
PMID 35750681 ↗
Moderate
Evidence against

What didn't work, and where the evidence is thin.

Every publication is incentivized to tell you a peptide works. We catalogue the null results, failed trials, and mechanism limits we found in the same literature — so you can weigh them against the upside, with your provider.

01
Entire pivotal evidence base is a single Chinese population
Mechanism limit
NEJM (GLORY-1) · 2025
GLORY-1 and every earlier mazdutide trial were conducted exclusively in Chinese adults, and the drug's only approval is in China. There is no Western phase 3 trial and no FDA or EMA approval.
What this means: Efficacy and safety may not transfer directly to other populations or diets, and regulatory acceptance elsewhere is unestablished. Treat the numbers as strong but geographically narrow.
PMID 40421736 ↗
02
Long-term cardiovascular and hepatic safety of glucagon agonism is unproven
Safety signal
Pharmacological Reviews (systematic review) · 2024
Reviews of the emerging obesity pipeline flag that mortality, cardiovascular, and long-term complication data are still needed for GLP-1/glucagon dual agonists. Glucagon agonism can raise heart rate and affect hepatic glucose handling, and no mazdutide cardiovascular-outcomes trial has reported.
What this means: The glucagon arm is what makes mazdutide potentially more effective and also what carries the least-characterized long-term risk. Hard-endpoint safety is not yet in evidence.
PMID 39952695 ↗
Part 06 · Cost & access

Where it's available, at what price.

China
Approved
Approved by the NMPA for weight management (2025); prescription-only.
Set within the Chinese market
United States
Investigational
Not FDA-approved; in clinical development. No legal consumer product.
N/A
European Union
Investigational
Not approved; no consumer access.
N/A
United Kingdom
Investigational
Not approved; no consumer access.
N/A
The Peptide Column takes no affiliate commission from any source. Mazdutide is approved only in China and is investigational elsewhere — any material sold to individuals outside China as "mazdutide" is unapproved and unregulated.
Part 07 · Your appointment

Questions to bring.

01
How does mazdutide compare to semaglutide or tirzepatide for my weight loss goals?
02
What are the unique risks of glucagon receptor activation in addition to GLP-1?
03
Is mazdutide available in my country, or is it still in clinical trials here?
04
What GI side effects should I expect, and how do they compare to other GLP-1 drugs?
05
How will mazdutide affect my blood sugar if I have diabetes?
06
What monitoring (liver function, lipids, glucose) is recommended during treatment?
References

Every citation, numbered.

Citation list. For our editorial read of each study — including bias flags and quality grades — see the Research log above.

  1. 01.
    GLORY-1 — once-weekly mazdutide in Chinese adults with obesity or overweight · New England Journal of Medicine, 2025 · PMID 40421736 ↗
  2. 02.
    Phase 2 mazdutide in Chinese overweight adults or adults with obesity · Nature Communications, 2023 · PMID 38092790 ↗
  3. 03.
    Phase 1b high-dose mazdutide (9 mg / 10 mg) in Chinese adults with overweight or obesity · EClinicalMedicine, 2022 · PMID 36247927 ↗
  4. 04.
    Phase 1b IBI362 (mazdutide) in Chinese patients with type 2 diabetes · Nature Communications, 2022 · PMID 35750681 ↗
  5. 05.
    ClinicalTrials.gov. GLORY-1 phase 3 (NCT05607680) · Source ↗
  6. 06.
    Innovent Biologics. Sponsor of the mazdutide (IBI362) program, partnered with Eli Lilly · Source ↗