# Mazdutide

GLP-1/glucagon dual agonist approved in China in 2025 (Xinermei); grey-market 'ghetto reta' with tirzepatide.

- Page: https://peprank.xyz/peptides/mazdutide
- Category: Metabolic & weight (Research peptide)
- Also known as: Xinermei (信尔美); IBI362; LY3305677; 'maz' / 'mazdu'
- Routes: Injection
- Safety tier: Strict: Avoid · Balanced: Avoid · Evidence only: Avoid
- Risk axes (0 none to 3 severe): Seen harm 2, Mechanism 3, Data gap 1, Silent harm 3, Product 3
- Positive: 55% of 21 graded reports glowing or positive, shrunk toward the 49% all-report average by 8 reports' weight
- Rank: #27 of 61 research peptides
- Graded reports: 21 (Positive 12, Mixed 4, Nothing 1, Negative 3, Bad reaction 1)
- Evidence: Approved drug — approved in China (NMPA, June 2025 for weight management, September 2025 for type 2 diabetes) on phase 3 GLORY and DREAMS trials in Chinese adults; Lilly's US phase 2 (n=179) has posted results; not FDA- or EMA-approved
- Access: Grey market
- Onset: Appetite and sugar cravings drop within the first one or two doses for some users; trial weight loss accrues over months.
- Lasts: Once-weekly injection; half-life about 10 days, so effects and side effects linger after stopping (the label asks women to stop 3 months before trying to conceive).
- Cost per month: ≈ €36–140 (researchers' estimate)
- Dose users report: 340–710 mcg/day (median 570 mcg, n=7)
- Updated: 2026-10-30

**Why Avoid under the strict bar:** Carries the GLP-1 class's serious-harm routes on its own label (pancreatitis, gallbladder disease, acute kidney injury, boxed warning for thyroid C-cell tumours in rodents) plus a glucagon-driven heart-rate rise; outside China it is bought as unregulated research vials and mostly stacked on tirzepatide, a combination no trial has tested.

## What users report

Twenty-two first-hand reports, nearly all mazdutide added to tirzepatide (the 'ghetto reta' stack) by people stalled on a GLP-1. Twelve are good (a thirteenth, from a coach's account, is flagged as vendor-adjacent): stalls broken, 'powered through the last 25 lbs', more energy, and several prefer it to survodutide as gentler on the gut and heart rate. Two US trial participants describe food noise gone and better blood pressure and lipids. Complaints are nausea and sleepiness in week one, diarrhoea at 6 mg, insomnia, a higher resting heart rate, dizziness from falling blood pressure, one case of emotional numbness, and one person who started at 3 mg and had palpitations with a resting rate near 130. Reports are few and confounded by tirzepatide. Felt nothing: 1 of 22 reports felt nothing; one US trial participant lost only 23 lb in five months at 10 mg..

**Effects:** weight loss of 14% at 48 weeks (6 mg) and 17% at 60 weeks (9 mg) in Chinese phase 3 trials; liver-fat, triglyceride, uric-acid and blood-pressure reductions beyond weight loss; appetite and sugar-craving suppression; users report more energy than on tirzepatide alone

**Downsides:** vomiting, nausea and diarrhoea (53%, 47% and 39% at 9 mg in GLORY-2); higher resting heart rate, mostly during dose escalation; insomnia; dizziness or fatigue as blood pressure falls; injection-site and allergic reactions (7-8% and 3-5% in GLORY-1)

**Risks:** Acute pancreatitis and acute gallbladder disease (label warnings; obstructive pancreatitis and cholecystitis in GLORY-1); Thyroid C-cell tumours in rodents at clinically relevant exposure (boxed warning); contraindicated with MTC or MEN 2; Heart-rate increase from glucagon-receptor agonism (mean up to 4.6 bpm; sinus tachycardia 4.5% at 6 mg vs 2.9%); Acute kidney injury from dehydration with severe GI effects (label); label says stop if resting heart rate stays raised; Label also warns of aspiration under anaesthesia and asks for monitoring of depression and suicidal thoughts (class precaution); Stacking on tirzepatide doubles GLP-1 load in an untested combination; vials of unknown dose and purity

**Caveat:** Almost all efficacy data come from young Chinese adults (mean age about 34) with modest baseline weight, and only the 9 mg trial ran past 48 weeks. The 2.6-4.6 bpm heart-rate rise eased during maintenance in trials, but users stacking it on tirzepatide report larger rises. Dose response is steep: 4 mg and 16 mg are very different drugs.

**Typical use:** China label: 2 mg weekly for 4 weeks, then 4 mg, then 6 mg if needed after at least 4 more weeks; maintenance 4 or 6 mg once weekly (a 9 mg dose was filed in November 2025). Lilly's US phase 2 went up to 16 mg. Grey-market users: 1-2 mg start, 3-5 mg weekly beside 5-15 mg tirzepatide.

**Getting it:** A prescription drug in China (Xinermei pre-filled pens, launched July 2025); elsewhere sold as research vials, mostly 5-10 mg, shipped from Hong Kong or China and paid in crypto.

**Stacked with:** tirzepatide (The 'ghetto reta' stack, adding glucagon agonism to GLP-1/GIP; the commonest use outside China, never trialled.); cagrilintide (Occasionally added for appetite, making a four-receptor stack.); retatrutide (Not combined; users switch between them, since retatrutide already includes glucagon agonism.)

## Risk profile

- **Seen harm 2/3:** The Chinese label (2025) carries warnings for acute pancreatitis, acute gallbladder disease, severe GI reactions, acute kidney injury and sustained heart-rate rise, and the trials produced matching cases: one gallstone-induced obstructive pancreatitis and one acute cholecystitis on mazdutide in GLORY-1 (gallstones 2.0% vs 1.0%), severe GI reactions in 2.0%, and one acute cholecystitis at 16 mg in Lilly's US phase 2. No deaths reported. On Reddit, one user starting at double the label dose described palpitations with a resting rate near 130.
- **Mechanism 3/3:** The molecule itself caused thyroid C-cell adenomas and carcinomas in a 2-year rat study at exposures below the human dose (boxed warning; human relevance unknown), and as a GLP-1 receptor agonist it shares the class's in-human pancreatitis and gallbladder harms. Glucagon-receptor agonism adds a heart-rate rise (mean up to 4.6 bpm in escalation, 2.6 bpm at 48 weeks; sinus tachycardia 4.5% at 6 mg vs 2.9%).
- **Data gap 1/3:** Approved in China (NMPA, June and September 2025) on phase 3 trials with about 2,000 participants (GLORY-1, GLORY-2, DREAMS-1, DREAMS-2), plus Lilly's 179-person US phase 2. Not approved by a stringent regulator, post-marketing experience is about a year and almost all trial participants were young Chinese adults; no data on stacking it with tirzepatide, which is how grey-market users take it.
- **Silent harm 3/3:** The feared harm the mechanism points at includes thyroid C-cell tumours, which would be silent and delayed; under the rubric a theoretical tumour pathway scores 3. The other harms are mixed: pancreatitis and cholecystitis present acutely, while gallstones and a raised resting heart rate build up unnoticed without imaging or a monitor.
- **Product 3/3:** In China it is a pharmacy pre-filled pen, but outside China what people buy is grey-market lyophilised vials shipped from Hong Kong or China, reconstituted at home and stacked on tirzepatide. Users report supplier-to-supplier differences in effect, and the dose is set by the vendor's label claim.
- **Never if:** Personal or family history of medullary thyroid carcinoma or MEN 2 (label); Pregnancy, planned pregnancy within 3 months, or breastfeeding (label); Known hypersensitivity to mazdutide or its excipients (label); History of acute gallbladder disease or severe GI disease such as gastroparesis (not recommended on the label); History of pancreatitis; Tachyarrhythmias, atrial fibrillation or other conditions where a higher resting heart rate is dangerous; History of suicidal thoughts or attempts (label advises avoiding it); Under 18

## Top reports

- Positive, metabolic: “I’m on Tirz/Maz now and it works for me as I’m now close to target. Zero sides.” — [r/Mazdutide](https://www.reddit.com/r/Mazdutide/comments/1pvajmc/pep_stacking_tirz_maz_or_survo/nvuwoye/)
- Positive, metabolic, up to 3 mg/week with 10 mg tirzepatide: “Everything I've read said Survo should deliver better results than Maz, but in my personal subjective experience, nothing has shed pounds more effectively than the stack of Tirz with Maz.” — [r/Mazdutide](https://www.reddit.com/r/Mazdutide/comments/1nr6eaa/maz_vs_survo/ngca16v/)
- Positive, metabolic, 5 mg/week with 10 mg tirzepatide: “I changed to mazdu and had appetite suppression again, plus I’m seeing faster weight loss.” — [r/Mazdutide](https://www.reddit.com/r/Mazdutide/comments/1hmxc2j/weight_loss_success/m418x9z/)
- Positive, metabolic: “Maz was like Reta-lite and, combined with Tirz, just powered through the last 25 lbs I needed to lose.” — [r/Mazdutide](https://www.reddit.com/r/Mazdutide/comments/1nr6eaa/maz_vs_survo/ngl8qd1/)
- Positive, metabolic: “I’ve got Survo on hand but I’ve stuck with Maz since it’s working and gives me energy.” — [r/Mazdutide](https://www.reddit.com/r/Mazdutide/comments/1nr6eaa/maz_vs_survo/ngdmyiq/)

## Studies

- [Ji et al. 2025: GLORY-1, once-weekly mazdutide in Chinese adults with obesity or overweight (NEJM)](https://pubmed.ncbi.nlm.nih.gov/40421736/) (rct, n=610, 2025): Weight fell 11.0% (4 mg) and 14.0% (6 mg) vs +0.3% on placebo at 48 weeks; half the 6 mg group lost 15% or more, with only 0.5-1.5% stopping for adverse events.
- [Gao et al. 2026: GLORY-2, 9 mg mazdutide in Chinese adults with obesity (JAMA)](https://pubmed.ncbi.nlm.nih.gov/42251595/) (rct, n=461, 2026): At 60 weeks 9 mg cut weight 16.7% vs 1.5% on placebo; vomiting 53%, nausea 47% and diarrhoea 39%, but only 2.9% stopped for adverse events.
- [Eli Lilly: phase 2 study of LY3305677 in adults with obesity or overweight (NCT06124807, posted results)](https://clinicaltrials.gov/study/NCT06124807) (rct, n=179, 2026): In the US trial weight fell 7.3% (3/6 mg), 15.6% (10 mg) and 18.1% (16 mg) vs 0.9% on placebo at 32 weeks; one acute cholecystitis at 16 mg among few serious events.
- [Shirley 2025: Mazdutide, first approval (Drugs)](https://pubmed.ncbi.nlm.nih.gov/41028652/) (review, 2025): Summarises the June 2025 Chinese approval for chronic weight management and the development programme run by Innovent with Eli Lilly.
- [Mazdutide (IBI362) 9 mg and 10 mg in Chinese adults with overweight or obesity: multiple-ascending-dose phase 1b (eClinicalMedicine 2022)](https://doi.org/10.1016/j.eclinm.2022.101691) (rct, 2022): Doses up to 10 mg were tolerated with no serious adverse events or discontinuations, supporting the higher-dose GLORY-2 trial.

## Sources

- [Innovent: mazdutide approved by China's NMPA for chronic weight management (27 Jun 2025)](https://en.innoventbio.com/InvestorsAndMedia/PressReleaseDetail?key=546)
- [Innovent (HKEX): mazdutide approved for type 2 diabetes (19 Sep 2025)](https://www1.hkexnews.hk/listedco/listconews/sehk/2025/0919/2025091900814.pdf)
- [Xinermei (mazdutide) Chinese prescribing information, Innovent](https://img.innoventbio.com/product/W10030842001.pdf)
- [Ji et al. 2025, GLORY-1 (NEJM)](https://doi.org/10.1056/NEJMoa2411528)
- [Gao et al. 2026, GLORY-2 (JAMA)](https://jamanetwork.com/journals/jama/article-abstract/2850143)
- [FDA: concerns with unapproved GLP-1 drugs used for weight loss](https://www.fda.gov/drugs/drug-alerts-and-statements/fdas-concerns-unapproved-glp-1-drugs-used-weight-loss)