Mazdutide
The world's first approved dual GLP-1/glucagon receptor agonist, developed by Innovent Biologics (China) with Eli Lilly holding ex-China rights. Approved in China for obesity and type 2 diabetes. The Phase 3 GLORY-2 trial (JAMA 2026) reported 16.7% mean weight loss at 9 mg over 60 weeks; a US Phase 2 trial reported up to 18.1% at 16 mg over 32 weeks.
Mazdutide is a once-weekly injection that activates two gut-hormone receptors at once — GLP-1, which cuts appetite, and glucagon, which raises energy expenditure and burns liver fat. In June 2025 it became the first drug of that specific combination approved anywhere, in China, where it is sold as Xinermei. In its largest published trial, people on 9 mg lost about 16.7% of their body weight over 60 weeks. It is not approved in the US or Europe, Eli Lilly has not filed for it there, and anything sold as mazdutide outside China is not the licensed product.
What is Mazdutide?
Mazdutide (IBI362/LY3305677, brand name Xinermei) is a synthetic oxyntomodulin analog carrying a C20 fatty-diacid side chain that extends its half-life enough for once-weekly subcutaneous dosing. It is a dual agonist of both GLP-1 and glucagon receptors — the same broad mechanism as survodutide, though a distinct molecule. It was not developed independently in China: Eli Lilly discovered it as LY3305677 and exclusively licensed it to Innovent Biologics for China in 2019, with Lilly retaining rights elsewhere. In June 2025, it became the world's first approved dual GCG/GLP-1 receptor agonist when China's NMPA approved it for weight management, followed by type 2 diabetes approval in September 2025. The peer-reviewed GLORY-2 Phase 3 trial (JAMA, August 2026) reported a mean 16.65% weight loss at 9 mg over 60 weeks versus 1.50% on placebo. The DREAMS-3 head-to-head trial against semaglutide has published only its protocol and baseline paper on PubMed; the sponsor has reported outcomes but a peer-reviewed results paper is not yet indexed. Mazdutide has also been studied outside China. A Lilly-funded, 32-patient US Phase 1 published in November 2025 reported 20.0% and 21.0% mean weight loss at 20 weeks on 16 mg, and a 179-patient US Phase 2 published in August 2026 reported up to 18.1% at 16 mg over 32 weeks. Mazdutide is not FDA or EMA approved and no US filing has been announced.
What Mazdutide Is Investigated For
Mazdutide is studied for obesity and type 2 diabetes as a once-weekly dual GLP-1/glucagon receptor agonist — a mechanistic inversion of tirzepatide's GLP-1/GIP dual agonism, built on oxyntomodulin biology with added glucagon-mediated energy expenditure and hepatic fat oxidation. The strongest evidence is the Phase 3 GLORY and DREAMS programs: GLORY-2 (JAMA 2026) showed 16.65% mean weight loss at 9 mg over 60 weeks versus 1.50% on placebo, GLORY-1 showed 14.0% at 6 mg over 48 weeks, and a 2026 meta-analysis of 9 RCTs (2,292 participants) estimated about 11% placebo-adjusted weight loss at 6 mg, though it rated the certainty very low; the DREAMS-3 head-to-head trial against semaglutide has published only its protocol and baseline paper on PubMed — sponsor-reported outcomes favor mazdutide, but peer-reviewed results are pending. In June 2025, it became the world's first approved dual GCG/GLP-1 receptor agonist when China's NMPA approved it as Xinermei, with type 2 diabetes approval following in September 2025. The key caveats: mazdutide is not FDA or EMA approved and Eli Lilly (which holds ex-China rights) has not announced a US filing, although it funded a 24-site US Phase 2 trial (Lancet Diabetes Endocrinol, August 2026) that tested doses up to 16 mg — well above the Chinese label. No completed cardiovascular outcomes trial, no dedicated MASH/MASLD trial despite the glucagon-agonism rationale, all Phase 3 trials enrolled exclusively Chinese participants, and grey-market 'mazdutide' sold outside China cannot be assumed to match the Innovent product on sequence, purity, or potency.
History & Discovery
Mazdutide was discovered and developed by Eli Lilly under the code LY3305677 as part of Lilly's broader exploration of oxyntomodulin-derived dual GLP-1/glucagon receptor agonists. In August 2019, Lilly entered an exclusive licence with Innovent Biologics to develop and commercialise the molecule, then called OXM3, in China; Innovent advanced it under the code IBI362 through a comprehensive Chinese clinical program. Innovent's own announcements consistently describe the territory simply as China, so the commonly repeated formulation naming Greater China plus Hong Kong, Macau and Taiwan should be treated as unsourced. The GLORY (obesity) and DREAMS (type 2 diabetes) Phase 3 trial families were run in Chinese populations and read out across 2024 and 2025. China's NMPA approved mazdutide for chronic weight management in June 2025 — the first regulatory approval anywhere of a dual GLP-1/glucagon agonist — and added a type 2 diabetes indication in September 2025 under the brand name Xinermei. The peer-reviewed record caught up through 2025 and 2026: GLORY-1 in NEJM (June 2025), DREAMS-1 and DREAMS-2 in Nature (April 2026), and GLORY-2 in JAMA (August 2026), which reported a mean 16.65% weight loss at 9 mg over 60 weeks — lower than the roughly 20% figure that circulated in earlier coverage. Lilly retains rights outside Greater China and has not announced a US or EU regulatory filing, but in August 2026 it published a 24-centre US Phase 2 trial (Hsia et al., Lancet Diabetes Endocrinol) testing doses up to 16 mg, the first mazdutide data in a non-Chinese population. Whether that leads to a Western Phase 3 program alongside Lilly's own tirzepatide and retatrutide is not yet public.
How It Works
Mazdutide activates two receptors: GLP-1 (which reduces appetite and improves blood sugar) and glucagon (which increases energy expenditure and promotes fat burning in the liver). The combination means you eat less AND burn more — a dual approach that neither receptor alone achieves as effectively.
Mazdutide is a synthetic analog of oxyntomodulin, a naturally occurring gut hormone that activates both GLP-1R and GCGR. A C20 fatty-diacid side chain, attached to a lysine side chain through a glutamate and two short spacers, extends the half-life enough for once-weekly dosing. GLP-1R activation in the hypothalamus suppresses appetite, in the pancreas enhances glucose-dependent insulin secretion, and in the GI tract slows gastric emptying. GCGR activation in hepatocytes increases fatty acid oxidation and energy expenditure while promoting glycogenolysis. Phase 3 results: GLORY-1 (610 patients, 48 weeks) showed 14.0% weight loss at 6 mg with 49.5% achieving at least 15%. GLORY-2 (461 treated, 60 weeks) showed a mean 16.65% weight loss at 9 mg versus 1.50% on placebo. DREAMS-1 (320 patients, 24 weeks) showed an absolute HbA1c reduction of 2.15% at 6 mg, 2.02 percentage points greater than placebo. DREAMS-3 (n≈349, 32-week head-to-head vs semaglutide) has published its protocol and baseline data on PubMed; peer-reviewed outcomes are not yet indexed. Outside China, the US Phase 2 trial (179 participants, 24 centres) reported 32-week weight changes of −7.3% (3–6 mg), −15.6% (10 mg), and −18.1% (16 mg) versus −0.9% on placebo, with further reductions by week 48 — evidence that the dose-response continues well above the 6 mg Chinese label ceiling.
Evidence Snapshot
Human Clinical Evidence
Strong for Chinese populations. Multiple Phase 3 RCTs published in NEJM, Nature, and JAMA. GLORY-1 (n=610, obesity): 14.0% weight loss at 6 mg. GLORY-2 (n=461 treated, obesity, JAMA 2026): 16.65% at 9 mg over 60 weeks vs 1.50% placebo. DREAMS-1 (n=320, T2D): absolute HbA1c -2.15% at 6 mg, placebo-adjusted -2.02 percentage points. DREAMS-2 (n=731, T2D): superior to dulaglutide. DREAMS-3 (n=349, T2D, vs semaglutide): protocol published; the sponsor reports superiority on a combined endpoint, but peer-reviewed outcomes are not yet indexed. US Phase 2 (n=179, Lancet Diabetes Endocrinol 2026): up to 18.1% at 16 mg over 32 weeks — the first published trial outside China. A 2026 meta-analysis of 9 RCTs (n=2,292) estimated −11.1% placebo-adjusted weight change at 6 mg (very low certainty). Approved by China's NMPA for both obesity and T2D.
Animal / Preclinical
Supportive. Oxyntomodulin biology and dual GCG/GLP-1 agonism well-established from preclinical pharmacology. Clinical data now the primary evidence base.
Mechanistic Rationale
Strong. Dual GCG/GLP-1 agonism is well-validated by both mazdutide and survodutide clinical programs. The addition of glucagon receptor activation to GLP-1 provides mechanistically distinct energy expenditure and hepatic fat oxidation benefits.
Research Gaps & Open Questions
What the current literature has not yet settled about Mazdutide:
- 01Cardiovascular outcomes — no cardiovascular outcomes trial has been completed or even registered for mazdutide, so whether it produces MACE reduction comparable to semaglutide (SELECT) and tirzepatide (SURPASS-CVOT) is entirely unestablished. Smaller cardiac studies exist (heart failure with preserved ejection fraction, coronary plaque), but none is powered for events.
- 02Long-term safety beyond Phase 3 trial durations — pancreatitis, gallbladder disease, diabetic retinopathy progression, and rare oncologic signals require multi-year exposure data.
- 03Generalizability beyond Chinese populations — all Phase 3 trials enrolled exclusively Chinese participants. The non-Chinese evidence is two Lilly trials, a 32-person Phase 1 and a 179-person Phase 2, neither large or long enough to settle efficacy and safety in other populations. A completed 308-person US Phase 2 in alcohol use disorder has not been published.
- 04Tolerability at higher doses — vomiting affected 53.1% of GLORY-2 participants on 9 mg, and 20% of US Phase 2 participants on 16 mg stopped treatment because of adverse events. Whether slower titration can make the higher, more effective doses practical is untested.
- 05Peer-reviewed DREAMS-3 results. The semaglutide head-to-head completed on 17 September 2025 and has published only its protocol and baseline paper, so the sponsor's superiority claim cannot yet be independently evaluated. Two design features matter when it is: the comparator was semaglutide 1 mg, a type 2 diabetes dose rather than the 2.4 mg obesity dose, and the trial was open-label.
- 06Hepatic-specific outcomes. Preclinical work in MASLD models shows mazdutide attenuates hepatic ER stress, inflammation and lipid accumulation, and a second independent mouse replication appeared in October 2026 — but no human liver trial has reported. This gap is closing faster than the literature suggests: a 181-patient Phase 2 in MASH passed primary completion on 23 September 2026, and a 479-patient Phase 3 against semaglutide in metabolic dysfunction-associated fatty liver disease is due to complete on 31 December 2026. Both are Innovent-run and Chinese.
- 07A published head-to-head efficacy comparison with tirzepatide or retatrutide. A 98-patient Chinese Phase 1/2 study of mazdutide 15 mg with a tirzepatide comparator arm completed in September 2026, but its endpoints were tolerability and pharmacokinetics and nothing has been reported; no retatrutide comparison exists at all.
- 08Body-composition effects (lean mass loss vs. fat-mass loss) at the 9 mg high dose are not yet published in detail.
Forms & Administration
Mazdutide is administered as a once-weekly subcutaneous injection, approved in China at up to 6 mg for both weight management and type 2 diabetes. The maintenance doses carried through the pivotal programs were 4 mg and 6 mg — GLORY-1 randomized participants to 4 mg, 6 mg or placebo, and DREAMS-1 did the same — with 3 mg and 4.5 mg functioning as titration steps rather than endpoints. GLORY-2 went to 9 mg, a supplementary application for which was accepted for review in late 2025 and has not been approved. Doses above that have only been studied outside the label: 10 mg and 16 mg in the US, and 15 mg in an ongoing Chinese study. Dose escalation over several weeks is standard to minimize GI side effects. Currently only available in China as Xinermei.
Dosing & Protocols
The ranges below reflect protocols commonly discussed in the literature and by clinicians — not a prescription. Actual dosing for any individual should be determined by a qualified healthcare provider who knows the patient.
Typical Range
Mazdutide is dosed once weekly subcutaneously, reaching maintenance through a stepwise titration in which 3 mg and 4.5 mg are intermediate steps. The pivotal trials in both indications used 4 mg and 6 mg as maintenance doses, and the Chinese approval tops out at 6 mg for weight management and for type 2 diabetes alike. Phase 3 GLORY-2 also tested a 9 mg maintenance dose for obesity, which produced a 16.65% mean weight loss at 60 weeks but is not currently in the approved label. The US Phase 2 trial went higher still, to 10 mg and 16 mg, neither of which is approved anywhere.
Frequency
Once weekly subcutaneous injection on the same day each week, with or without regard to meals. The C20 fatty-diacid acylation enables a half-life consistent with weekly dosing.
Timing Considerations
No specific timing requirements: can be administered at any time of day, with or without food, and is not tied to exercise timing. Consistency matters more than the specific clock — dose at roughly the same time each day (or same day each week, for weekly protocols) to keep exposure steady.
Cycle Length
Mazdutide is intended for chronic, indefinite use in both obesity and type 2 diabetes. It is not a cycled or short-course intervention. Discontinuation kinetics have not been characterized in the published Chinese trials, but based on the broader incretin class, substantial weight regain within 6–12 months of stopping should be expected.
Protocol Notes
Outside mainland China, mazdutide is not commercially available through any legitimate channel. Lilly has not announced a US or EU filing, and no FDA-approved generic, compounded, or imported version exists in the United States. Material sold under the mazdutide name on grey-market sites, including 'research-chemical' suppliers, is not the licensed Innovent product, has not been bioequivalence-tested, and may differ in sequence, salt form, purity, or potency. The Chinese-label dosing schedule is the only formally validated regimen.
Mazdutide is not approved by the FDA or EMA. The dosing described above reflects the Chinese label and trial protocols, not US prescribing guidance. Use outside an authorized clinical or licensed prescribing context is unsupervised and unregulated.
Timeline of Effects
Onset
Reduced appetite and early weight loss are typically reported within the first 2–4 weeks of dosing, consistent with the GLP-1 mechanism. Glycemic improvements in the DREAMS trials emerged within the first month and continued to deepen through the titration period.
Peak Effect
In GLORY-2 (9 mg, 60 weeks), mean weight loss reached 16.65% at the week-60 primary endpoint. In GLORY-1 (6 mg, 48 weeks), mean weight loss plateaued closer to 14%. In the US Phase 2 trial, weight was still falling between week 32 and week 48 at the higher doses, so the true plateau at 10–16 mg is not yet known. HbA1c reductions in DREAMS-1 reached approximately -2.0 percentage points at 6 mg by month 6.
After Discontinuation
Discontinuation kinetics have not been formally reported in the published GLORY/DREAMS data. Based on the GLP-1/glucagon class and parallels to STEP-1 follow-up data for semaglutide, the working assumption is that two-thirds or more of lost weight is regained within 12 months of cessation, with HbA1c, blood pressure, and lipid markers also reverting toward baseline.
Monitoring & Measurement
Bloodwork & Labs
- •HbA1c and fasting glucose — the registration endpoints in type 2 diabetes, and worth tracking in weight-management use because the glucagon arm acts on hepatic glucose output
- •Liver enzymes (ALT, AST) and, where available, liver fat by MRI-PDFF or transient elastography — the glucagon component's distinctive claim is hepatic fat oxidation, and the human liver trials have not yet reported
- •Lipid panel, including triglycerides
- •Heart rate and blood pressure — incretin agents raise resting heart rate modestly as a class
- •Lipase or amylase only when pancreatitis is clinically suspected; routine screening is not recommended
Functional & Performance Tests
- •Body weight and waist circumference at every titration step
- •Body composition by DEXA where available — the proportion of weight lost as lean mass at the 9 mg dose has not been published in detail, which is one of this page's open questions
When to Test
Baseline, then at each dose escalation during titration, then at roughly 3-month intervals once on a maintenance dose.
Interpretation & Notes
The tolerability profile is the practical constraint rather than efficacy. Vomiting affected 53.1% of participants on 9 mg in GLORY-2 against 1.3% on placebo, and in the US Phase 2 one in five participants on 16 mg stopped because of adverse events — so the doses that produce the headline weight-loss figures are also the ones people struggle to stay on. Slower titration is the standard mitigation and is why the approved schedule steps through 3 mg and 4.5 mg. Because glucagon receptor agonism transiently increases hepatic glucose output, anyone on insulin or a sulfonylurea needs those doses reviewed at initiation and at each escalation.
Common Questions
How does mazdutide compare to tirzepatide?
Different dual mechanisms. Tirzepatide targets GIP + GLP-1 receptors. Mazdutide targets glucagon + GLP-1 receptors. In their Phase 3 programs, tirzepatide 15 mg produced roughly 20–22% weight loss at 72 weeks (SURMOUNT-1), while mazdutide 9 mg produced 16.65% at 60 weeks (GLORY-2) — but the trials differ in population, duration, and dose, so this is not a like-for-like comparison. The US Phase 2 trial of mazdutide reached 18.1% at 16 mg after only 32 weeks, which hints that higher doses could close the gap. The glucagon component in mazdutide may provide additional benefits for liver fat and energy expenditure, while tirzepatide's GIP component may enhance insulin secretion differently. A direct comparison has now been run, though not as an efficacy trial: NCT07000955, a 98-patient Chinese Phase 1/2 study of mazdutide 15 mg, carried a tirzepatide active-comparator arm and reached primary completion on 30 September 2026. Its endpoints are tolerability and pharmacokinetics, and no results have been published.
Is mazdutide available outside China?
Not yet. Eli Lilly holds rights to mazdutide outside China but has not announced US or EU regulatory filings. Lilly did fund a 179-person US Phase 2 trial across 24 centres (Hsia et al., Lancet Diabetes Endocrinol, August 2026) that tested 3–6 mg, 10 mg, and 16 mg, so a Western development path is being explored — but a Phase 2 trial is several years and a full Phase 3 program away from approval. Currently only available in China as Xinermei.
How does mazdutide compare to survodutide?
Both are dual GLP-1/glucagon agonists derived from oxyntomodulin. Mazdutide is further in development (approved in China, multiple Phase 3 trials complete). Survodutide (Boehringer Ingelheim) is still in Phase 3 globally. Mazdutide has published active-comparator data against dulaglutide (DREAMS-2), while its semaglutide head-to-head (DREAMS-3) has so far published only a protocol; survodutide has notable MASH/liver data.
Why do some sources say mazdutide causes 20% weight loss?
Both numbers are real, and they describe different analyses of the same trial rather than loose journalism. Innovent's own November 2025 GLORY-2 release reported a mean 18.55% weight reduction at week 60 on 9 mg, and 20.08% in the subgroup without type 2 diabetes. The peer-reviewed GLORY-2 publication (Gao et al., JAMA, August 2026) reports a mean 16.65% weight loss at 60 weeks with mazdutide 9 mg versus 1.50% with placebo — a placebo-adjusted difference of about 15.15 percentage points — across the full treated population of 461 Chinese adults, 16.1% of whom had type 2 diabetes; 84.3% lost at least 5% of body weight. So the lower figure is the whole trial and the higher one is a subgroup of it. Higher figures still exist at unapproved doses: 20.0% and 21.0% at 20 weeks on 16 mg in a 32-person US Phase 1. When numbers conflict, the peer-reviewed full-population result is the one to quote.
How well tolerated is mazdutide?
Gastrointestinal side effects are common and dose-related. In GLORY-2, vomiting was reported by 53.1% of participants on 9 mg versus 1.3% on placebo, yet only 2.9% stopped treatment because of adverse events. In the US Phase 2 trial, stopping because of adverse events was most frequent at the highest dose, affecting 20% of participants on 16 mg. Slow titration is the main way these effects are managed in practice.
Who Mazdutide Is NOT For
- •Personal or family history of medullary thyroid carcinoma (MTC) — boxed warning class effect across GLP-1 receptor agonists based on rodent C-cell tumor findings.
- •Multiple Endocrine Neoplasia syndrome type 2 (MEN2) — same mechanistic concern as MTC.
- •Active pancreatitis or history of recurrent pancreatitis — rare class-level pancreatitis signals support precautionary avoidance.
- •Pregnancy — no human pregnancy safety data; the long half-life and developmental concerns of the incretin class make use during pregnancy or for at least two months before a planned pregnancy inadvisable.
- •Breastfeeding — no human lactation data.
- •Severe gastroparesis or other significant GI motility disorders — both GLP-1 and glucagon receptor agonism affect GI physiology.
- •Insulinoma or other conditions of inappropriate hyperinsulinemia — glucagon agonism can complicate already dysregulated counter-regulatory physiology.
Drug & Supplement Interactions
The two clinically important interaction domains parallel those of semaglutide and other GLP-1 agonists. First, hypoglycemia risk increases when mazdutide is combined with insulin or insulin secretagogues (sulfonylureas, meglitinides), and downward titration of those concomitant agents at mazdutide initiation and each escalation step is the standard mitigation. Second, the slowed gastric emptying induced by GLP-1 receptor activation alters the absorption rate and peak concentration of orally administered drugs, with particular attention warranted for narrow-therapeutic-index agents (warfarin, levothyroxine, oral contraceptives, antiepileptics). The added glucagon receptor agonism introduces an additional consideration: transient elevations in hepatic glucose output and lipolysis could theoretically interact with chronic medications affecting hepatic metabolism, though this has not been systematically characterized in the published trial data. Patients prescribed mazdutide in China should disclose all concurrent medications to their prescriber.
Safety Profile
Common Side Effects
Cautions
- • Approved only in China — not FDA or EMA approved
- • GI side effects are dose-dependent; slower titration improves tolerability
- • Glucagon receptor activation may raise hepatic glucose output transiently
- • Long-term safety data beyond clinical trial durations is limited
What We Don't Know
Cardiovascular outcomes data is not yet available. Whether the glucagon component confers additional liver or metabolic benefits beyond GLP-1 alone in long-term use is still being studied. Western market safety data and regulatory review have not occurred.
Legal Status
United States
Mazdutide is not FDA-approved and has no announced US regulatory filing. Lilly holds the rights outside China and has run and published both a US Phase 1 and a US Phase 2 trial, but has not announced a US Phase 3 program. It is not legally available through US compounding pharmacies, telehealth providers, or any other domestic channel. Personal importation from China is not legal under FDA rules and is enforced inconsistently.
International
Approved in mainland China by the NMPA for chronic weight management (June 2025) and type 2 diabetes (September 2025) as Xinermei. Not approved by the EMA, UK MHRA, Health Canada, Australia's TGA, or any other major regulator outside China. No public timeline exists for ex-China filings.
Sports & Competition
Mazdutide is not named on the 2026 or 2027 WADA Prohibited List. WADA's S0 'Non-approved substances' category does not apply, because S0 covers only substances with no current approval by any government regulatory health authority, and China's NMPA has approved mazdutide. It is not named in S2 (peptide hormones, growth factors, related substances and mimetics) either, so, like approved GLP-1 receptor agonists, it is not currently prohibited. Athletes subject to WADA, USADA, or equivalent codes should confirm status with their anti-doping organization before use, as the list is updated annually.
Regulatory status changes over time. Verify current local rules with a qualified professional.
Myths & Misconceptions
Myth
Mazdutide is FDA-approved or available in the US.
Reality
It is approved only in mainland China. Lilly holds ex-China rights but has not filed in the US or EU, and there is no legal pathway for compounding pharmacies, telehealth platforms, or grey-market suppliers to provide mazdutide domestically.
Myth
Because it adds glucagon agonism to GLP-1, mazdutide raises blood sugar and is dangerous for diabetics.
Reality
The DREAMS Phase 3 program in type 2 diabetes patients showed substantial HbA1c reductions — DREAMS-1 reported about −2.0 percentage points at 6 mg, and DREAMS-2 showed superiority over dulaglutide. (The sponsor also reports a win over semaglutide in DREAMS-3, but those results are not yet peer-reviewed.) The GLP-1 component dominates net glycemic effect; the glucagon component contributes hepatic fat oxidation and energy expenditure benefits without producing net hyperglycemia at therapeutic doses.
Myth
Mazdutide and survodutide are effectively the same drug.
Reality
Both are dual GLP-1/glucagon receptor agonists derived from oxyntomodulin biology, but they are distinct molecules with different sequences, receptor potencies, and developers (Innovent/Lilly vs. Boehringer Ingelheim). They have not been compared head-to-head, and their development trajectories differ — mazdutide is approved in China, survodutide is in global Phase 3.
Myth
Grey-market 'mazdutide' sold by research-chemical suppliers is the same as Xinermei.
Reality
Xinermei is the licensed Innovent product manufactured under regulated pharmaceutical conditions. Material sold under the mazdutide name outside China cannot be assumed to share sequence, salt form, purity, or potency with the approved drug, and is not authorized for human use anywhere.
Published Research
18 studiesThe GLP-1R/GCGR Dual Agonist Mazdutide Attenuates Liver Steatosis and Decreases Circulating Cholesterol Levels in Mice With Metabolic Dysfunction-Associated Steatotic Liver Disease.
The Power of Two: Harnessing Dual Glucagon and Incretin Signaling for Treatment of Obesity and Metabolic Dysfunction-Associated Steatohepatitis-A Narrative Review with a Translational Focus.
Efficacy and Safety of Dual GLP-1/Glucagon Receptor Agonism in Overweight and Obesity: A Class-Specific Systematic Review and Meta-Analysis.
Efficacy and safety of mazdutide in adults with obesity or overweight: a US-based, multicentre, phase 2, randomised, placebo-controlled clinical trial.
Hsia et al., Lancet Diabetes Endocrinol, August 2026 — the largest mazdutide trial published outside China, and the second after Lilly's 32-patient Phase 1 (179 participants, 24 US centres). 32-week weight change: −7.3% (3–6 mg), −15.6% (10 mg), −18.1% (16 mg) vs −0.9% placebo, with further reductions at 48 weeks; adverse-event discontinuation highest at 16 mg (20%).
Comparative effects of drugs for adults with overweight or obesity: systematic review and network meta-analysis.
Efficacy and Safety of the Dual Glucagon-Like Peptide-1 and Glucagon Receptor Agonist Mazdutide in Predominantly Chinese Adults With Obesity and/or Type 2 Diabetes: A Systematic Review and Meta-Analysis.
Treatment With 9-mg Mazdutide for Weight Reduction in Chinese Adults With Obesity: The GLORY-2 Randomized Clinical Trial.
GLORY-2 (Gao et al., JAMA, August 2026) — 461 Chinese adults with moderate-to-severe obesity. Mean weight change at 60 weeks was −16.65% on mazdutide 9 mg vs −1.50% on placebo; 84.3% lost ≥5%. Vomiting 53.1% vs 1.3%; 2.9% discontinued for adverse events. Supersedes the higher ~20% figure quoted in earlier coverage.
Mazdutide ameliorates metabolic dysfunction-associated steatotic liver disease by modulating endoplasmic reticulum stress, improving lipid metabolism and alleviating inflammation.
Mazdutide 9 mg in Chinese adults with a body mass index ≥30 kg/m2 but without diabetes: A phase 2 randomized controlled trial.
Phase 2 RCT (n=80) supporting the 9 mg maintenance dose later carried into GLORY-2; mean ~12.8% weight loss at 24 weeks vs. ~1.8% weight gain on placebo in non-diabetic Chinese adults with BMI ≥30.
Mazdutide versus dulaglutide in Chinese adults with type 2 diabetes (DREAMS-2).
Mazdutide versus placebo in Chinese adults with type 2 diabetes (DREAMS-1).
DREAMS-1 (Zhu et al., Nature 2026) — the placebo-controlled phase 3 T2D trial behind mazdutide's September 2025 NMPA approval, alongside the DREAMS-2 dulaglutide comparator. 320 participants randomized 1:1:1 to 4 mg, 6 mg or placebo for 24 weeks: HbA1c fell 1.57% and 2.15% versus 0.14% on placebo, placebo-adjusted differences of 1.43 and 2.02 percentage points. DREAMS-3 did not support this approval — it reached primary completion two days before it.
Mazdutide versus Semaglutide for the treatment of type 2 diabetes and obesity: Rationale, design and baseline data of DREAMS-3 phase 3 trial.
Mazdutide: First Approval.
Mazdutide reduces body weight in adults with overweight or obesity: A high-dose Phase 1 trial.
Bhattachar et al., Diabetes Obes Metab 2025 — the Lilly-run US Phase 1 that is both the earliest published mazdutide trial outside China and the source of the highest weight-loss figures in the literature. 32 adults with overweight or obesity, once-weekly mazdutide to 16 mg or placebo for 20 weeks: mean weight change −20.0% and −21.0% in the two cohorts versus −0.1% on placebo, with at least 15% lost by 66.7% and 75.0% of participants. No serious adverse events. The cohorts are tiny, so this sets an upper bound on what high doses might do rather than establishing it.
Mazdutide, a dual agonist targeting GLP-1R and GCGR, mitigates diabetes-associated cognitive dysfunction: mechanistic insights from multi-omics analysis.
Once-Weekly Mazdutide in Chinese Adults with Obesity or Overweight (GLORY-1).
GLORY-1 (Ji et al., NEJM 2025) — the pivotal phase 3 obesity trial that supported China's NMPA approval of mazdutide in June 2025, the first regulatory approval anywhere of a dual GLP-1/glucagon receptor agonist.
Safety and efficacy of GLP-1 and glucagon receptor dual agonist for the treatment of type 2 diabetes and obesity: a systematic review and meta-analysis of randomized controlled trials.
IBI362 (LY3305677), a weekly-dose GLP-1 and glucagon receptor dual agonist, in Chinese adults with overweight or obesity: A randomised, placebo-controlled, multiple ascending dose phase 1b study.
Quick Facts
- Class
- Incretin Mimetic
- Tier
- B
- Evidence
- Moderate
- Safety
- Limited Data
- Updated
- Nov 2026
- Citations
- 18PubMed
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