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Survodutide vs Mazdutide: What the Research Shows

Last updated 2026-09-10
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Survodutide and mazdutide are the two most clinically advanced members of a new peptide class: dual agonists that activate the glucagon receptor and the GLP-1 receptor at the same time. The class logic is shared — pair GLP-1's appetite-suppressing "energy-in" mechanism with glucagon's hepatic "energy-out" mechanism — but the two molecules reached that receptor pair by different routes, come from different developers, and have been tested on largely different continents. Mazdutide, discovered by Eli Lilly and taken through phase 3 in China by Innovent Biologics, became the first dual glucagon/GLP-1 receptor agonist approved anywhere when China's NMPA cleared it for chronic weight management in June 2025, with a type 2 diabetes approval following that September [12][13][14]. Survodutide, from Boehringer Ingelheim and Zealand Pharma, remains investigational in every market but holds FDA Breakthrough Therapy designation for non-cirrhotic MASH and has published phase 3 obesity data from an international program [6][11].

One thing must be stated up front: no head-to-head trial of survodutide versus mazdutide exists, and none has been announced. Everything below compares trial results, never the compounds themselves. The two programs enrolled different populations, ran for different durations, and analyzed results under different estimands — cross-trial numbers can describe each program, but they cannot rank the molecules.

For full compound detail, see the survodutide research overview and the mazdutide research overview.

Side-by-Side Comparison

Survodutide (BI 456906) Mazdutide (IBI362 / LY3305677)
Molecular design Glucagon-derived backbone engineered for balanced GCGR/GLP-1R dual agonism; selected from 19 candidates by biomarker profiling [1] Fatty-acylated analog of oxyntomodulin, a natural gut hormone that is itself a dual agonist; acylation supports once-weekly dosing [12]
Developer Boehringer Ingelheim + Zealand Pharma [1] Discovered by Eli Lilly; developed through phase 3 in China by Innovent Biologics [12]
Regulatory status Investigational everywhere; FDA Breakthrough Therapy designation for non-cirrhotic MASH (Oct 2024) [11] Approved in China for chronic weight management (Jun 2025) and type 2 diabetes (Sep 2025); investigational in the US, where Lilly's program is at phase 2 [13][14][21]
Key obesity trial results Phase 2: −14.9% at 46 wk (4.8 mg) vs −2.8% placebo [2]. Phase 3 SYNCHRONIZE-1 (76 wk): −13.0% at 6.0 mg by treatment-regimen estimand vs −5.4% placebo; up to −16.6% by efficacy estimand [6][7] Phase 3 GLORY-1 (48 wk): −14.01% at 6 mg vs +0.30% placebo [15]. GLORY-2 (9 mg, 60 wk): −16.65% by treatment-policy analysis, up to −20.1% on treatment [16][17]. US phase 2 (32 wk): −18.1% at 16 mg [21]
Key type 2 diabetes results Phase 2 (16 wk): HbA1c down up to 1.71 points; 0.9 mg matched open-label semaglutide 1.0 mg [3]. Phase 3 SYNCHRONIZE-2 results pending [9] Phase 3 DREAMS-1 (24 wk): HbA1c −2.15 points at 6 mg vs −0.14 placebo [18]. DREAMS-2: superior to dulaglutide 1.5 mg on HbA1c and weight [19]. DREAMS-3 topline: superior to semaglutide 1 mg on a composite endpoint [20]
Liver / MASH data Biopsy-based phase 2 in MASH F1–F3: histologic improvement without worsening of fibrosis in up to 62% vs 14% placebo [4]; fibrosis effect mostly weight-independent in mediation analysis [5]. Phase 3 SYNCHRONIZE-MASLD (imaging): ≥30% liver-fat reduction in 84.2% vs 24.3% by efficacy estimand [8]. Biopsy-based LIVERAGE phase 3 trials ongoing [11] Imaging-based only: in GLORY-1 participants with baseline liver fat ≥10%, mean relative liver-fat reduction of ~80% at 6 mg vs ~5% placebo [22]. Steatotic liver disease studies announced but not yet published [12]
Evidence depth & trial geography International phase 3 program (SYNCHRONIZE-1: 725 adults; CVOT enrolling ~4,935) plus regional trials in Japan and China; biopsy-confirmed MASH phase 2 in 293 adults [4][6][9][10] All phase 3 data from Chinese cohorts (GLORY-1: 610; GLORY-2: 461; DREAMS-1/-2: 320/731); US evidence limited to a 179-participant phase 2 trial [15][16][18][19][21]

Why Pair Glucagon with GLP-1 at All?

Both molecules answer the same design question. GLP-1 receptor activation enhances glucose-dependent insulin secretion, slows gastric emptying, and reduces appetite — the semaglutide mechanism. Glucagon receptor agonism adds something a pure incretin cannot: increased hepatic energy expenditure and lipid oxidation, acting directly on the liver [1][23]. Because glucagon signaling alone raises blood glucose, both compounds were engineered so the incretin arm counterbalances that effect [1][12]. This distinguishes the pair from tirzepatide, whose second target is GIP (another incretin), and overlaps with two-thirds of the triple agonist retatrutide [1][23].

Two Routes to the Same Receptor Pair

The lineages differ in a way that is chemically interesting even if its clinical significance is unproven. Survodutide is a product of rational engineering: Boehringer scientists started from a glucagon backbone and screened 19 dual-agonist candidates using biomarker readouts — glucose-tolerance testing for GLP-1 receptor engagement, FGF21 and hepatic gene expression for glucagon receptor engagement — to select the activity ratio that maximized weight-lowering in obese mice without sacrificing glucose control [1]. Mazdutide instead borrows nature's template: oxyntomodulin, a post-meal gut hormone that already activates both receptors but survives only minutes in circulation. A fatty-acid side chain promoting albumin binding stretches that duration to a week [12]. Both approaches converge on the same pharmacological problem — tuning the glucagon-to-GLP-1 activity balance — from opposite ends.

The Obesity Programs: SYNCHRONIZE vs GLORY

Survodutide's phase 3 SYNCHRONIZE-1 randomized 725 adults for 76 weeks: mean weight change of −13.0% at 6.0 mg by the treatment-regimen estimand (counting everyone randomized) versus −5.4% with placebo, and an average of −16.6% among participants who adhered to treatment [6][7]. Mazdutide's GLORY-1 randomized 610 Chinese adults for 48 weeks, reporting −14.01% at 6 mg versus +0.30% with placebo [15]; GLORY-2 tested a higher 9 mg dose over 60 weeks in moderate-to-severe obesity, reporting −16.65% by treatment-policy analysis and up to −20.1% on treatment [16][17]. A US phase 2 trial tested mazdutide up to 16 mg, with −18.1% at 32 weeks [21].

These figures sit side by side here, but they are not interchangeable. The populations differ — GLORY-1's mean baseline BMI was 31.1, lower than typical Western phase 3 obesity cohorts, while SYNCHRONIZE-1 enrolled internationally [6][15]. Durations differ (48 vs 60 vs 76 weeks). And the headline number each program reports depends on the estimand: survodutide's 13.0%/16.6% split and mazdutide's 16.65%/20.1% split are the same phenomenon — different estimands address different questions and can produce different estimates — so quoting one program's efficacy-estimand figure against another's treatment-policy figure misleads in either direction [6][7][16][17].

The Diabetes Programs

Mazdutide's diabetes evidence is further along in print: DREAMS-1 reported HbA1c reductions of 2.15 points at 24 weeks in Chinese adults with a mean baseline HbA1c of 8.24% [18], DREAMS-2 showed superiority over dulaglutide 1.5 mg [19], and topline DREAMS-3 results reported superiority over semaglutide 1 mg on a composite of glycemic control plus at least 10% weight reduction — with the caveats that the comparator was semaglutide's lower diabetes dose and the full dataset is not yet peer-reviewed [20]. Survodutide's published diabetes data are phase 2: HbA1c reductions up to 1.71 points over 16 weeks, with the 0.9 mg dose matching open-label semaglutide 1.0 mg [3]; the phase 3 SYNCHRONIZE-2 design is described separately [9]. Baseline HbA1c, trial duration, and background therapy all differ across these trials, so the HbA1c figures are not directly comparable.

Liver Disease: Different Depths of Evidence

Both programs report striking liver findings, consistent with the glucagon receptor's direct hepatic activity — but the evidence tiers differ. Survodutide has biopsy-confirmed data: in its phase 2 MASH trial, up to 62% of participants showed histologic improvement without worsening of fibrosis versus 14% on placebo [4], and a 2026 mediation analysis estimated that only 36.3% of the fibrosis benefit was mediated by weight reduction [5]. That result earned Breakthrough Therapy designation and launched the multi-year, biopsy-based LIVERAGE phase 3 program [11], alongside the imaging-based SYNCHRONIZE-MASLD readout [8]. Mazdutide's liver data are imaging-only so far: GLORY-1 subgroup analyses showed roughly 80% relative reduction in MRI-measured liver fat at 6 mg among participants with baseline liver fat of 10% or more [22], and steatotic liver disease is a stated research direction without published trial results [12]. Large liver-fat reductions on imaging and biopsy-based MASH improvement are distinct endpoints. The cited survodutide trial tested histologic improvement without worsening fibrosis [4]; that should not be relabeled as MASH resolution. The mediation estimate [5] also depends on modeling assumptions and does not by itself prove a weight-independent molecular mechanism.

Reading Across the Two Programs

  • Geography is the biggest confounder. All mazdutide phase 3 data come from Chinese cohorts; survodutide's phase 3 data are international [6][15][21]. Baseline BMI, body composition, and diet differ across these populations.
  • Estimands drive headlines. Compare treatment-policy with treatment-policy, efficacy with efficacy — never across [6][16].
  • Regulatory status reflects geography, not a verdict on the science. Chinese NMPA approval and FDA review are separate processes on separate datasets [13][14].
  • Outcome trials diverge. Survodutide has a dedicated cardiovascular outcomes trial enrolling roughly 4,935 adults [10]; no cardiovascular or kidney outcomes trial has been reported for mazdutide [12].
  • Both share the class tolerability profile. Dose-related gastrointestinal adverse events dominated every trial in both programs [2][4][6][15][16].

References

  1. Thomas L, et al. The dual GCGR/GLP-1R agonist survodutide: Biomarkers and pharmacological profiling for clinical candidate selection. Diabetes Obes Metab. 2024;26(6):2368–2378. doi:10.1111/dom.15551. PMID: 38560764
  2. le Roux CW, et al. Glucagon and GLP-1 receptor dual agonist survodutide for obesity: a randomised, double-blind, placebo-controlled, dose-finding phase 2 trial. Lancet Diabetes Endocrinol. 2024;12(3):162–173. doi:10.1016/S2213-8587(23)00356-X. PMID: 38330987
  3. Blüher M, et al. Dose-response effects on HbA1c and bodyweight reduction of survodutide, a dual glucagon/GLP-1 receptor agonist, compared with placebo and open-label semaglutide in people with type 2 diabetes: a randomised clinical trial. Diabetologia. 2024;67(3):470–482. doi:10.1007/s00125-023-06053-9. PMID: 38095657
  4. Sanyal AJ, et al. A Phase 2 Randomized Trial of Survodutide in MASH and Fibrosis. N Engl J Med. 2024;391(4):311–319. doi:10.1056/NEJMoa2401755. PMID: 38847460
  5. Noureddin M, et al. Weight reduction-dependent/-independent effects of survodutide on liver endpoints: Mediation analysis of a phase 2 trial in MASH. Hepatology. 2026 (online ahead of print). doi:10.1097/HEP.0000000000001825. PMID: 42545725
  6. le Roux CW, et al. Survodutide Once Weekly for the Treatment of Adults with Obesity. N Engl J Med. 2026;395(8):776–787. doi:10.1056/NEJMoa2600751. PMID: 42253238
  7. Zealand Pharma / Boehringer Ingelheim. Zealand Pharma announces Boehringer Ingelheim's novel glucagon/GLP-1 dual agonist survodutide achieved significant weight loss of 16.6% delivering meaningful metabolic improvement in people with obesity or overweight in Phase 3 trial (SYNCHRONIZE-1). Press release, April 2026. https://www.biospace.com/press-releases/zealand-pharma-announces-boehringer-ingelheims-novel-glucagon-glp-1-dual-agonist-survodutide-achieved-significant-weight-loss-of-16-6-delivering-meaningful-metabolic-improvement-in-people-with-obesity-or-overweight-in-phase-3-trial
  8. Kaplan LM, et al. Survodutide in adults with obesity and metabolic dysfunction-associated steatotic liver disease: SYNCHRONIZE-MASLD, a randomized, double-blind, placebo-controlled phase 3 trial. Nat Med. 2026;32(8):2948–2958. doi:10.1038/s41591-026-04479-3. PMID: 42252333
  9. Wharton S, et al. Survodutide for treatment of obesity: rationale and design of two randomized phase 3 clinical trials (SYNCHRONIZE™-1 and -2). Obesity (Silver Spring). 2025;33(1):67–77. doi:10.1002/oby.24184. PMID: 39495965
  10. Kosiborod MN, et al. Survodutide for the Treatment of Obesity: Rationale and Design of the SYNCHRONIZE Cardiovascular Outcomes Trial. JACC Heart Fail. 2024;12(12):2101–2109. doi:10.1016/j.jchf.2024.09.004. PMID: 39453356
  11. Boehringer Ingelheim. Boehringer receives U.S. FDA Breakthrough Therapy designation and initiates two phase III trials in MASH for survodutide (LIVERAGE; LIVERAGE-Cirrhosis). Press release, October 2024. https://www.biospace.com/press-releases/boehringer-receives-u-s-fda-breakthrough-therapy-designation-and-initiates-two-phase-iii-trials-in-mash-for-survodutide
  12. Shirley M. Mazdutide: First Approval. Drugs. 2025;85(12):1621–1627. doi:10.1007/s40265-025-02249-y. PMID: 41028652
  13. Innovent Biologics. Innovent Announces Mazdutide, First Dual GCG/GLP-1 Receptor Agonist, Received Approval from China's NMPA for Chronic Weight Management. Press release, June 27, 2025. https://www.prnewswire.com/news-releases/innovent-announces-mazdutide-first-dual-gcgglp-1-receptor-agonist-received-approval-from-chinas-nmpa-for-chronic-weight-management-302493152.html
  14. Innovent Biologics. Innovent Announces Mazdutide Received Approval from China's NMPA for Glycemic Control in Adults with Type 2 Diabetes. Press release, September 2025. https://www.prnewswire.com/news-releases/innovent-announces-mazdutide-received-approval-from-chinas-nmpa-for-glycemic-control-in-adults-with-type-2-diabetes-302561434.html
  15. Ji L, et al. Once-Weekly Mazdutide in Chinese Adults with Obesity or Overweight (GLORY-1). N Engl J Med. 2025;392(22):2215–2225. doi:10.1056/NEJMoa2411528. PMID: 40421736
  16. Gao L, et al. Treatment With 9-mg Mazdutide for Weight Reduction in Chinese Adults With Obesity: The GLORY-2 Randomized Clinical Trial. JAMA. 2026;336(5):377–388. doi:10.1001/jama.2026.8142. PMID: 42251595
  17. Innovent Biologics. Mazdutide 9 mg Achieves Up to 20.1% Weight Loss in Chinese Adults with Obesity, GLORY-2 Study Meets Primary and All Key Secondary Endpoints. Press release, November 2025. https://www.prnewswire.com/news-releases/mazdutide-9-mg-achieves-up-to-20-1-weight-loss-in-chinese-adults-with-obesity-glory-2-study-meets-primary-and-all-key-secondary-endpoints-302620471.html
  18. Zhu D, et al. Mazdutide versus placebo in Chinese adults with type 2 diabetes (DREAMS-1). Nature. 2026;652(8108):174–180. doi:10.1038/s41586-025-10026-w. PMID: 41407859
  19. Guo L, et al. Mazdutide versus dulaglutide in Chinese adults with type 2 diabetes (DREAMS-2). Nature. 2026;652(8108):181–188. doi:10.1038/s41586-025-10031-z. PMID: 41407860
  20. Innovent Biologics. Innovent's Mazdutide Shows Superiority in Glycemic Control with Weight Loss over Semaglutide in a Head-to-head Phase 3 Clinical Trial DREAMS-3. Press release, October 26, 2025. https://www.prnewswire.com/news-releases/innovents-mazdutide-shows-superiority-in-glycemic-control-with-weight-loss-over-semaglutide-in-a-head-to-head-phase-3-clinical-trial-dreams-3-302594633.html
  21. Hsia SH, et al. Efficacy and safety of mazdutide in adults with obesity or overweight: a US-based, multicentre, phase 2, randomised, placebo-controlled clinical trial. Lancet Diabetes Endocrinol. 2026. doi:10.1016/S2213-8587(26)00160-9. PMID: 42628555
  22. Innovent Biologics. Phase 3 Clinical Study of Mazdutide in Chinese Adults with Overweight or Obesity (GLORY-1) Published in The New England Journal of Medicine. Press release, May 2025. https://www.prnewswire.com/news-releases/phase-3-clinical-study-of-mazdutide-in-chinese-adults-with-overweight-or-obesity-glory-1-published-in-the-new-england-journal-of-medicine-nejm-302464859.html
  23. Elmendorf AJ, et al. IUPHAR review: From foe to friend: Repurposing glucagon to treat obesity and type 2 diabetes. Pharmacol Res. 2026;223:108077. doi:10.1016/j.phrs.2025.108077. PMID: 41478576

This article summarizes published scientific literature for educational purposes only. Survodutide is an investigational compound not approved for human use anywhere. Mazdutide is approved in China for chronic weight management and type 2 diabetes; in the United States it is an investigational compound not approved by the FDA for any use. Nothing here constitutes medical advice, and no statement has been evaluated by the FDA.

Disclaimer: Research materials supplied by Limitless Labs are intended strictly for in-vitro research and laboratory use only. They are not intended for human or animal consumption, therapeutic use, or any form of self-administration. They are not approved medicines. Where this library discusses an approved pharmaceutical, that product is distinct from research materials sold by Limitless Labs. This page is an educational summary of published research and is not medical advice. These statements have not been evaluated by the Food and Drug Administration.

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