Key papers ✓ 8~ 1? 1

• ✓ Positive human RCTN Engl J Med · 2026

  Survodutide Once Weekly for the Treatment of Adults with Obesity.

  Humans725 peopleRandomizedPlacebo-controlledDouble-blind76 weeks

  Phase 3 double-blind randomized trial (SYNCHRONIZE-1), 1:1:1

  In 725 adults with obesity without diabetes (SYNCHRONIZE-1), survodutide reduced weight by 12.2-13.0% at 76 weeks vs 5.4% with placebo; GI symptoms in 80.9-89.7% vs 47.9%.

  Key resultMean body weight change -12.2% (3.6 mg), -13.0% (6.0 mg) vs -5.4% (placebo); at least 5% weight reduction in 72.6%, 71.9% and 46.3% (P<0.001 for all vs placebo)

  Study details

  Studied

  Adults with BMI ≥30, or ≥27 with an obesity-related complication, without diabetes (mean age 47.1)

  Compared with

  Placebo plus lifestyle counseling

  Main outcome

  Percent change in body weight and weight reduction of at least 5% at week 76

  Sample

  725 participants (241 survodutide 3.6 mg, 242 survodutide 6.0 mg, 242 placebo)

  Authors' conclusion

  Survodutide led to significantly greater body weight reductions than placebo in adults with obesity without diabetes.

  Limitations

  Gastrointestinal adverse events in 80.9% and 89.7% vs 47.9% with placebo; participants without diabetes only; sponsor-funded.

  DOI 10.1056/NEJMoa2600751PubMed 42253238
• ✓ Positive human RCTN Engl J Med · 2026

  Survodutide Once Weekly in Adults with Obesity and Type 2 Diabetes.

  Humans752 peopleRandomizedPlacebo-controlledDouble-blind76 weeks

  Multinational, double-blind, placebo-controlled phase 3 RCT (1:1:1)

  In 752 adults with obesity and type 2 diabetes (SYNCHRONIZE-2, phase 3), 76 weeks of survodutide cut weight by 8.2% (3.6 mg) and 9.8% (6.0 mg) vs 3.9% with placebo; 57.6% and 64.5% lost at least 5% vs 35.1%.

  Key resultMean weight change -8.2% (3.6 mg), -9.8% (6.0 mg) vs -3.9% placebo; at least 5% loss in 57.6%, 64.5% vs 35.1%

  Study details

  Studied

  Adults with type 2 diabetes and BMI of 27 or more (mean age 55.7 years, mean BMI 36.5)

  Compared with

  Placebo

  Main outcome

  Percent change in body weight and weight loss of at least 5% at week 76

  Sample

  752 randomized (250 survodutide 3.6 mg, 251 survodutide 6.0 mg, 251 placebo)

  Authors' conclusion

  Survodutide at 3.6 mg or 6.0 mg weekly produced significantly greater weight reduction than placebo in adults with obesity and type 2 diabetes.

  Limitations

  Industry-funded; abstract does not report adverse event rates.

  DOI 10.1056/NEJMoa2607219PubMed 42820639
• ✓ Positive human RCTNat Med · 2026

  Survodutide in adults with obesity and metabolic dysfunction-associated steatotic liver disease: SYNCHRONIZE-MASLD, a randomized, double-blind, placebo-controlled phase 3 trial.

  Humans216 peopleRandomizedPlacebo-controlledDouble-blind48 weeks

  Randomized, double-blind, placebo-controlled phase 3 trial

  In 216 adults with obesity and at-risk MASLD/MASH (SYNCHRONIZE-MASLD, phase 3), 84.2% on survodutide vs 24.3% on placebo had at least 30% liver-fat reduction at 48 weeks, with weight -12.2% vs -1.0%; GI events were the most common adverse events.

  Key resultAt least 30% liver-fat reduction in 84.2% vs 24.3% (P<0.0001, efficacy estimand); weight -12.2% vs -1.0%

  Study details

  Studied

  Adults with obesity and at-risk MASLD/MASH

  Compared with

  Placebo

  Main outcome

  At least 30% reduction in MRI-PDFF liver fat and percent change in body weight

  Sample

  216 randomized 2:1 (146 survodutide 6.0 mg, 70 placebo)

  Authors' conclusion

  Survodutide was statistically and clinically superior to placebo for liver fat and body weight reduction; GI adverse events were mostly mild to moderate and occurred during dose escalation.

  Limitations

  Short duration (48 weeks); participants recruited only in the United States and Spain.

  DOI 10.1038/s41591-026-04479-3PubMed 42252333Free full text
• ✓ Positive meta-analysisDiabetes Obes Metab · 2026

  Efficacy and Safety of Dual GLP-1/Glucagon Receptor Agonism in Overweight and Obesity: A Class-Specific Systematic Review and Meta-Analysis.

  Humanssize not reported19 RCTs pooled

  Systematic review and random-effects meta-analysis (PROSPERO registered) with GRADE assessment

  Class-specific meta-analysis of 19 RCTs of GLP-1/glucagon dual agonists (including survodutide): weight fell by 7.15% more than control and serious adverse events did not differ (RR 0.90), though any adverse event was more frequent (RR 1.16); it covers several drugs, not survodutide alone.

  Key resultRelative weight MD -7.15%; at least 5% weight loss RR 4.75; any adverse event RR 1.16; serious adverse events RR 0.90

  Study details

  Studied

  Adults with overweight or obesity in RCTs of GLP-1/glucagon dual agonists

  Compared with

  Placebo or control

  Main outcome

  Body weight, 5% weight loss, metabolic markers, adverse events

  Sample

  19 RCTs of mazdutide, survodutide, cotadutide and efinopegdutide

  Authors' conclusion

  Dual GLP-1/GCGR agonists produce meaningful weight loss and metabolic improvements with acceptable short-term safety, though longer head-to-head trials are needed for durability and cardiovascular safety.

  Limitations

  Pools different drugs; certainty of some outcomes low to moderate.

  DOI 10.1111/dom.71400PubMed 42811393
• ✓ Positive meta-analysisDiabetol Metab Syndr · 2024

  Effect of survodutide, a glucagon and GLP-1 receptor dual agonist, on weight loss: a meta-analysis of randomized controlled trials.

  Humans1,029 people

  Systematic review and random-effects meta-analysis to August 2024

  Meta-analysis of survodutide RCTs (18 treatment arms, 1,029 participants): weight fell 8.33 kg more than control, with larger effects at higher doses and over longer treatment; heterogeneity was very high (I2 above 99%).

  Key resultWeight WMD -8.33 kg (95% CI -10.80 to -5.86; I2 = 99.6%); BMI -4.03 kg/m2; waist -6.33 cm

  Study details

  Studied

  Participants in randomized trials of injectable survodutide

  Compared with

  Control group

  Main outcome

  Weight, BMI and waist circumference

  Sample

  18 treatment arms, 1029 participants

  Authors' conclusion

  Survodutide is effective in reducing weight, BMI and waist circumference, especially with longer interventions and higher doses.

  Limitations

  Very high heterogeneity (I2 up to 99.6%); mixes trial populations and doses.

  DOI 10.1186/s13098-024-01501-xPubMed 39508238Free full text
• ✓ Positive human RCTN Engl J Med · 2024

  A Phase 2 Randomized Trial of Survodutide in MASH and Fibrosis.

  Humans293 peopleRandomizedPlacebo-controlled48 weeks

  Phase 2 randomized trial, 1:1:1:1, survodutide 2.4, 4.8 or 6.0 mg weekly

  In 293 adults with biopsy-confirmed MASH and fibrosis, 48 weeks of survodutide improved MASH without worsening fibrosis in 43-62% vs 14% with placebo; nausea 66% vs 23%, vomiting 41% vs 4%.

  Key resultMASH improvement in 47% (2.4 mg), 62% (4.8 mg) and 43% (6.0 mg) vs 14% with placebo (P<0.001 for the quadratic dose-response curve)

  Study details

  Studied

  Adults with biopsy-confirmed MASH and fibrosis stage F1 through F3

  Compared with

  Placebo

  Main outcome

  Histologic improvement in MASH with no worsening of fibrosis

  Sample

  293 randomized participants received at least one dose

  Authors' conclusion

  Survodutide was superior to placebo for improving MASH without worsening fibrosis, warranting phase 3 trials.

  Limitations

  Phase 2; nausea (66% vs 23%), diarrhea (49% vs 23%) and vomiting (41% vs 4%) more frequent with survodutide.

  DOI 10.1056/NEJMoa2401755PubMed 38847460
• ~ Mixed human RCTLancet Diabetes Endocrinol · 2024

  Glucagon and GLP-1 receptor dual agonist survodutide for obesity: a randomised, double-blind, placebo-controlled, dose-finding phase 2 trial.

  Humans387 peopleRandomizedPlacebo-controlledDouble-blind46 weeks

  Randomised, double-blind, placebo-controlled, dose-finding phase 2 trial

  In 386 adults with obesity, survodutide reduced weight by 6.2-14.9% at 46 weeks vs 2.8% with placebo, but GI adverse events affected 75% (vs 42%) and only about 60% of participants completed treatment.

  Key resultBodyweight change -6·2% (0·6 mg), -12·5% (2·4 mg), -13·2% (3·6 mg), -14·9% (4·8 mg) vs -2·8% with placebo

  Study details

  Studied

  Adults aged 18-75 with BMI ≥27 kg/m2 without diabetes, 43 centres in 12 countries

  Compared with

  Placebo

  Main outcome

  Percentage change in bodyweight from baseline to week 46

  Sample

  387 enrolled; 386 treated (77-78 per arm); 233 completed

  Authors' conclusion

  All tested survodutide doses were tolerated and dose-dependently reduced bodyweight.

  Limitations

  About 40% did not complete treatment; adverse events in 91% vs 75% with placebo, mostly gastrointestinal.

  DOI 10.1016/S2213-8587(23)00356-XPubMed 38330987
• ✓ Positive human RCTDiabetologia · 2024

  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.

  Humans413 peopleRandomizedPlacebo-controlledDouble-blind16 weeks

  Phase II multicentre randomised, double-blind, placebo-controlled, parallel-group dose-response study with open-label semaglutide arm

  In 413 people with type 2 diabetes, 16 weeks of survodutide lowered HbA1c by up to 1.71% (similar to semaglutide at low dose) and weight by up to 8.7%; adverse events in 77.8% vs 52.5% on placebo.

  Key resultHbA1c fell up to -18.72 mmol/mol (-1.71%) with survodutide; bodyweight fell up to -8.7% (DG6) vs -5.3% with semaglutide

  Study details

  Studied

  Adults aged 18-75 with type 2 diabetes on metformin, HbA1c 7.0-10.0%, BMI 25-50 kg/m2

  Compared with

  Placebo and open-label semaglutide (up to 1.0 mg weekly)

  Main outcome

  Absolute change in HbA1c at 16 weeks; relative bodyweight change

  Sample

  413 participants randomised (8 arms)

  Authors' conclusion

  Survodutide reduced HbA1c and bodyweight after 16 weeks in type 2 diabetes; dose-related gastrointestinal adverse events could be mitigated by slower dose escalation.

  Limitations

  Short 16-week duration; semaglutide arm was open-label.

  DOI 10.1007/s00125-023-06053-9PubMed 38095657Free full text
  Fig. 1 Fig. 2
• ? Inconclusive human trialJ Hepatol · 2024

  Efficacy, tolerability and pharmacokinetics of survodutide, a glucagon/glucagon-like peptide-1 receptor dual agonist, in cirrhosis.

  Humanssize not reportedOpen-label28 weeks in multiple-dose cohorts

  Multinational, non-randomized, open-label phase I trial

  Open-label phase 1 study in people with cirrhosis and controls: drug exposure was similar regardless of cirrhosis, drug-related adverse events occurred in over 80% over 28 weeks, and liver fat and stiffness generally fell.

  Key resultMean AUC0-∞ and Cmax were similar in cirrhosis and healthy individuals; drug-related adverse events 82.4% and 87.5% in multiple-dose cohorts

  Study details

  Studied

  People with Child-Pugh A, B or C cirrhosis, healthy individuals, and people with overweight/obesity with or without cirrhosis

  Compared with

  Healthy individuals matched for age, sex and weight

  Main outcome

  Pharmacokinetics (AUC0-∞, Cmax) and drug-related adverse events

  Sample

  Single-dose cohorts n = 41; multiple-dose cohorts n = 41

  Authors' conclusion

  Survodutide is generally tolerable in compensated or decompensated cirrhosis, needs no pharmacokinetic dose adjustment, and may improve liver-related tests, supporting further study.

  Limitations

  Non-randomized, open-label phase I; efficacy markers were exploratory.

  DOI 10.1016/j.jhep.2024.06.003PubMed 38857788
• ✓ Positive animalMol Metab · 2022

  BI 456906: Discovery and preclinical pharmacology of a novel GCGR/GLP-1R dual agonist with robust anti-obesity efficacy.

  Humans + animals

  Preclinical in vitro and in vivo pharmacology

  In mice, survodutide produced greater weight loss than maximally effective semaglutide by both reducing food intake and increasing energy expenditure.

  Study details

  Studied

  Cell-based assays and mice (including GLP-1R knockout and transgenic reporter mice)

  Compared with

  Semaglutide

  Main outcome

  Functional receptor agonism, bodyweight, energy expenditure and food intake

  Authors' conclusion

  BI 456906 (survodutide) is a potent GCGR/GLP-1R dual agonist with robust anti-obesity efficacy through increased energy expenditure and decreased food intake; in mice it reduced bodyweight more than semaglutide.

  Limitations

  Preclinical (cells and mice); sample sizes not given in abstract.

  DOI 10.1016/j.molmet.2022.101633PubMed 36356832Free full text

Reported side effects

• commonGastrointestinal events (nausea, diarrhea, vomiting), dose-related [ref] [ref] [ref] [ref] [ref]
• commonDrug-related adverse events in people with cirrhosis [ref]
• uncommonSerious adverse events (similar to placebo) [ref] [ref]

Gastrointestinal intolerance is frequent; cardiovascular outcome data are not yet published in the candidates.

35 registered human trials (10 active)

✓ positive · ✗ negative · ~ mixed · ? inconclusive, judged on each paper's own main outcome. Grades: A strong human evidence → D little or none. Papers and verdicts are drawn from PubMed, Europe PMC and Russian journals (CyberLeninka); not medical advice.