Survodutide

• Often saidA phase 3 result means the medicine is approved

  ActuallyA successful trial and a marketing authorization are separate events. No marketing approval was established in the reviewed sources.

• Often saidThe liver program has already shown a fibrosis benefit

  ActuallyThe phase 2 MASH trial found clearer effects on MASH and liver fat than on fibrosis, and the phase 3 MASLD report found no between-group difference in liver stiffness.

Nobody is named here yet, because we have not done that work on this entry. Read that as unfinished. Somebody almost certainly sells this, and somebody almost certainly disputes it. Assume both until we have checked.

• On 16 August 2024, following an opinion from its Paediatric Committee on 28 June 2024, the European Medicines Agency accepted changes requested by Boehringer Ingelheim to its agreed paediatric investigation plan for survodutide for the treatment of obesity; the decision (P/0259/2024) is not a marketing authorisation. Under the modified plan, survodutide is to be studied in a randomised, double-blind, placebo-controlled study in children and adolescents aged 6 to under 18 with obesity or overweight, supported by models of how the drug moves through and acts in the body; the plan is due for completion by December 2032, with some measures deferred. The decision grants a waiver for children from birth to under 6 years because the product does not represent a significant therapeutic benefit over existing treatments, and Boehringer Ingelheim stated in information provided for the procedure that the product was not authorised anywhere in the European Community.

  European Medicines Agency, decision P/0259/2024

  A: High supportRegulatoryConfidence: highChecked 2026-09-07

• The phase 2 obesity trial of survodutide, registered at ClinicalTrials.gov as NCT04667377 and sponsored by Boehringer Ingelheim, was a randomized, double-blind, placebo-controlled study in adults aged 18 to 75 with a BMI of 27 or higher and without diabetes. It enrolled 387 people at 43 sites in 12 countries across Europe, North America, Asia and Oceania, began in March 2021 and was completed in October 2022. At 46 weeks, average body weight fell by 6.2, 12.5, 13.2 and 14.9 percent across the four survodutide groups, rising with dose, compared with 2.8 percent on placebo; 60.7 to 82.8 percent of people across the survodutide groups had lost at least 5 percent of their body weight, compared with 25.9 percent on placebo, and 33.9 to 68.8 percent had lost at least 10 percent, compared with 11.1 percent on placebo. Posted results report no deaths in any group; serious adverse events were recorded in 13 of 309 people who received survodutide and 5 of 77 who received placebo, while adverse events occurred in 91 percent and 75 percent, respectively, and were mainly stomach and gut effects, reported by 75 percent on survodutide and 42 percent on placebo. About 6 in 10 people completed treatment: 233 of 386 overall, 61 percent on survodutide and 60 percent on placebo.

  ClinicalTrials.gov, NCT04667377

  B: Moderate supportregistryConfidence: highChecked 2026-09-07

• SYNCHRONIZE-2 (NCT06066528) is a Boehringer Ingelheim phase 3, randomized, double-blind, placebo-controlled trial of survodutide in adults with overweight or obesity and type 2 diabetes. It enrolled 755 people at sites in 19 countries, with main measures of percent change in body weight and the share of people losing at least 5 percent of their body weight after 76 weeks. ClinicalTrials.gov lists the trial as completed, with collection of its main results finished on 12 December 2025 and the whole study finished on 1 April 2026; no results were posted on the record as of its 6 August 2026 update.

  ClinicalTrials.gov, NCT06066528

  A: High supportregistryConfidence: highChecked 2026-09-07

• SYNCHRONIZE-CVOT (NCT06077864) is a Boehringer Ingelheim phase 3, randomized, double-blind, placebo-controlled heart safety trial of survodutide that enrolled 5,531 adults with overweight or obesity and either established heart or kidney disease, or at least two weight-related complications or heart risk factors, at 540 listed sites in 35 countries and territories. Its main measure is the time to a first heart or blood vessel event (heart-related death, non-fatal stroke, non-fatal heart attack, a procedure to restore blood flow to the heart, or a heart failure event) to test whether survodutide is no worse than placebo on that risk; ClinicalTrials.gov lists the trial as completed on 30 June 2026, with no results posted as of the record’s 17 September 2026 update.

  ClinicalTrials.gov, NCT06077864

  A: High supportregistryConfidence: highChecked 2026-09-07

• LIVERAGE-Cirrhosis (ClinicalTrials.gov NCT06632457) is a Boehringer Ingelheim phase 3, randomized, double-blind, placebo-controlled trial of survodutide in adults whose MASH has progressed to compensated cirrhosis, planned for about 1,590 people at 446 listed sites in 36 countries and territories. Its main measure is time to a first serious liver outcome: death from any cause, liver transplant, a decompensation event, a MELD liver score rising to 15 or more, or progression to clinically significant portal hypertension. ClinicalTrials.gov lists the trial as recruiting, with main results estimated for 5 June 2029; no results were posted as of the record’s 18 September 2026 update.

  ClinicalTrials.gov, NCT06632457

  A: High supportregistryConfidence: highChecked 2026-09-07

• In donated human and mouse brain tissue, the GLP-1 receptor was found in the appetite-related area postrema and arcuate nucleus, while the glucagon receptor was barely detectable there when single cells were examined. The authors note that the human data are limited to receptor expression and that survodutide’s action was tested only in mice. In mice, fluorescent-labeled survodutide reached circumventricular organs and nearby appetite-related regions of the hypothalamus and hindbrain, without evidence that it crossed the blood-brain barrier throughout the brain, and switched on nerve cells in several regions linked to food-intake control. In mice with diet-induced obesity, a long-acting drug acting only on the glucagon receptor did not switch on nerve cells in appetite-control regions or reduce food intake, but still lowered body weight, which the authors attribute to raised energy expenditure; they read this as support that survodutide’s appetite effect runs through the GLP-1 receptor (Molecular Metabolism, 2026, DOI 10.1016/j.molmet.2026.102326).

  Molecular Metabolism, 2026, DOI 10.1016/j.molmet.2026.102326

  B: Moderate supportPrimary studyConfidence: highChecked 2026-09-07

• Survodutide, then called BI 456906, is a 29-amino-acid peptide made by modifying the human glucagon sequence; an amidated end and the unusual amino acid 1-aminocyclobutane-1-carboxylic acid (Ac4c) at position 2 help protect it from breakdown, while a C18 fatty diacid attached through a glycine-serine linker at position 24 binds albumin in the blood to lengthen its half-life. In cell tests, it activated both the human GLP-1 receptor and the human glucagon receptor; measured in human plasma, where its fatty acid chain binds albumin, it was about 8 times more potent at the GLP-1 receptor than at the glucagon receptor. In mice with diet-induced obesity, it lowered body weight by up to 32 percent over 28 days, more than semaglutide at the lower of two maximally effective doses, which gave 25 percent; compared with the higher semaglutide dose, which gave 27 percent, the difference was not statistically significant. In these mice, survodutide raised energy expenditure independent of body weight, with a statistically significant rise on days 7 and 8 in one dose group, without raising body temperature or physical activity; it initially cut food intake less sharply than semaglutide, and the authors concluded that its weight loss in mice came from both eating less and burning more energy.

  Zimmermann T, Thomas L, Baader-Pagler T, Haebel P, Simon E, Reindl W, et al. BI 456906: Discovery and preclinical pharmacology of a novel GCGR/GLP-1R dual agonist with robust anti-obesity efficacy. Mol Metab. 2022 Dec;66:101633. doi: 10.1016/j.molmet.2022.101633. PMID: 36356832.

  C: Limited supportPrimary studyChecked 2026-09-29

• Boehringer Ingelheim researchers selected survodutide as their clinical candidate from 19 dual glucagon and GLP-1 receptor agonists: in lean mice, markers of each receptor’s action tracked each compound’s strength at that receptor in cell tests, and three compounds, including survodutide, underwent in-depth testing before survodutide was chosen for its balanced action at the two receptors. In lean mice, survodutide and the two other finalists improved glucose tolerance about as much as semaglutide, while showing different degrees of glucagon receptor action in the liver, measured across the three compounds as a 15- to 17-fold rise in liver NNMT gene activity and up to a sevenfold rise in blood FGF21. In mice with diet-induced obesity, survodutide lowered body weight by 25 percent from baseline, close to the 27 and 26 percent seen with the other finalists; in diabetic db/db mice, survodutide and one related finalist lowered HbA1c by 0.4 to 0.6 percentage points, while the third finalist had no significant effect. The abstract does not state how long either mouse study lasted.

  Thomas L, Martel E, Rist W, Uphues I, Hamprecht D, Neubauer H, et al. The dual GCGR/GLP-1R agonist survodutide: Biomarkers and pharmacological profiling for clinical candidate selection. Diabetes Obes Metab. 2024 Jun;26(6):2368-2378. doi: 10.1111/dom.15551. PMID: 38560764.

  B: Moderate supportPrimary studyChecked 2026-09-29

• In obese mice, the survodutide-related backup compound BI-456908, not survodutide itself, produced about 40% weight loss at the higher of two tested doses over 4 weeks; this extra weight loss was largely lost in mice lacking the liver glucagon receptor, approaching the roughly 20% seen with semaglutide. In the same study, the increases in energy expenditure and decreases in blood amino acids seen in normal mice were blunted or absent in mice lacking the receptor, and the compound lowered liver fat in normal mice but not in receptor-lacking mice; its lowering of ALT did not depend on the receptor, and semaglutide did not lower liver fat. The compound improved glucose tolerance and lowered fasting blood sugar about as much as semaglutide in normal and receptor-lacking mice alike; the study was funded by Boehringer Ingelheim.

  Long F, Challa TD, Efthymiou V, Klug M, Klein T, Neubauer H, et al. Hepatic GCGR is required for the superior weight loss and metabolic effects of a structurally related analogue of the dual GCGR/GLP-1R agonist survodutide in mice. Diabetes Obes Metab. 2026 Mar;28(3):2437-2442. doi: 10.1111/dom.70359. PMID: 41388343.

  B: Moderate supportPrimary studyChecked 2026-09-29

• Survodutide, then called BI 456906, was compared with placebo in two phase 1 studies: a single-rising-dose study in 24 men with a BMI of 20 to under 30, and a repeated-rising-dose study over 6 or 16 weeks in 125 adults with a BMI of 27 to 40 (NCT03175211 and NCT03591718). In the repeated-dose study in adults with overweight or obesity, body weight fell compared with placebo by up to 5.79% at week 6 and up to 13.8% at week 16; in the single-dose study, average body weight fell more as the dose rose. In these phase 1 studies in people, survodutide lowered blood amino acids and glucagon, which the authors read as signs that it acted on both the glucagon receptor and the GLP-1 receptor. Drug-linked side effects increased with dose: in the single-dose study, decreased appetite was most common (9 people, printed as 50.0%), and 2 of 24 did not finish because of nausea and vomiting; in the 6-week part of the repeated-dose study, 10 of 80 stopped survodutide, most often for heart or blood vessel side effects (6 people), while in the 16-week part, 8 of 45 stopped, mainly for side effects, most commonly stomach and gut problems.

  Jungnik A, Arrubla Martinez J, Plum-Morschel L, Kapitza C, Lamers D, Thamer C, et al. Phase I studies of the safety, tolerability, pharmacokinetics and pharmacodynamics of the dual glucagon receptor/glucagon-like peptide-1 receptor agonist BI 456906. Diabetes Obes Metab. 2023 Apr;25(4):1011-1023. doi: 10.1111/dom.14948. PMID: 36527386.

  B: Moderate supportPrimary studyChecked 2026-09-29

• A randomized, placebo-controlled phase 1 trial tested survodutide, then called BI 456906, in 36 healthy Japanese men with overweight or obesity and a BMI of 23 to 40: three groups of 9 received doses raised step by step over 16 weeks, and 9 received placebo. After 16 weeks, body weight fell by 5.57, 12.37 and 9.62 percent in the three survodutide groups, while men on placebo gained 1.06 percent. Every man on survodutide had a side effect investigators linked to the drug, most often decreased appetite, compared with 4 men on placebo; 10 of the 27 men on survodutide stopped dose increases because of side effects (9 for decreased appetite and 1 for a rise in amylase), compared with none on placebo, and the authors reported no unexpected tolerability concerns. Paracetamol absorption was lower in week 1 in two of the three survodutide groups, which the authors interpreted as a short-lived delay in stomach emptying.

  Yazawa R, Ishida M, Balavarca Y, Hennige AM. A randomized Phase I study of the safety, tolerability, pharmacokinetics and pharmacodynamics of BI 456906, a dual glucagon receptor/glucagon-like peptide-1 receptor agonist, in healthy Japanese men with overweight/obesity. Diabetes Obes Metab. 2023 Jul;25(7):1973-1984. doi: 10.1111/dom.15064. PMID: 36974349.

  B: Moderate supportPrimary studyChecked 2026-09-29

• In a 16-week phase 2 trial in 413 adults with type 2 diabetes already taking metformin, survodutide lowered HbA1c by 0.91 to 1.71 percentage points across six dose groups, from an average starting level of 8.07%; a lower-dose group lowered HbA1c about as much as open-label semaglutide (1.46 versus 1.47 points), while the abstract does not print the placebo group’s HbA1c change. Body weight fell more at higher survodutide doses, by up to 8.7%, and higher-dose groups lost more weight than people on semaglutide, who lost 5.3%. Adverse events, mainly stomach and gut effects, were reported by 77.8% of people on survodutide, 52.5% on placebo and 52.0% on semaglutide. Side effects led 15.9% of people on survodutide to stop treatment, compared with 5.1% on placebo and 4.0% on semaglutide; most of these stops came within the first 6 weeks, which the authors link to the fast dose increases required by the 16-week design.

  Blüher M, Rosenstock J, Hoefler J, Manuel R, Hennige AM. 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 Mar;67(3):470-482. doi: 10.1007/s00125-023-06053-9. PMID: 38095657.

  B: Moderate supportPrimary studyChecked 2026-09-29

• In a 48-week phase 2 trial of 293 adults with biopsy-confirmed MASH and liver scarring (fibrosis stage F1 to F3), MASH improved without worsening scarring in 47%, 62%, and 43% of people in the three survodutide groups, compared with 14% on placebo, judged by liver biopsy; liver fat fell by at least 30% in 63%, 67%, and 57%, compared with 14%, and scarring improved by at least one stage in 34%, 36%, and 34%, compared with 22% on placebo, although the abstract gives no statistical test for this last comparison. Nausea (66% versus 23%), diarrhea (49% versus 23%), and vomiting (41% versus 4%) were more common on survodutide than on placebo, while serious adverse events occurred in 8% and 7%, respectively. A later statistical analysis of 170 people with fibrosis stage F2 to F3 estimated that weight loss accounted for 36.3% of survodutide’s effect on improving liver scarring, 66.7% of its effect on MASH resolution, and 71.8% of its effect on MASH improvement, judged by liver biopsy after 48 weeks. In the same post hoc analysis, which pooled dose groups, less than half of survodutide’s effect on blood and imaging tests of liver inflammation and scarring (16.5% to 38.6%) was estimated to run through weight loss, compared with 58.2% and 77.4% of its effect on liver fat on two measures; the authors called this suggestive of a direct role for glucagon receptor action in the liver.

  Sanyal AJ, Bedossa P, Fraessdorf M, Neff GW, Lawitz E, Bugianesi E, et al. A Phase 2 Randomized Trial of Survodutide in MASH and Fibrosis. N Engl J Med. 2024 Jul 25;391(4):311-319. doi: 10.1056/NEJMoa2401755. PMID: 38847460.

  C: Limited supportPrimary studyChecked 2026-09-29

• A phase 1, open-label, non-randomized trial in several countries (NCT05296733) studied survodutide in people with Child-Pugh class A, B or C cirrhosis and matched healthy people; after a single injection, blood levels were similar in people with cirrhosis and healthy people across 41 people in the single-dose groups. Investigators linked side effects occurred in 25.0% of healthy people and at most 25.0% of people with cirrhosis after a single injection, and in 82.4% of those without cirrhosis and 87.5% of those with cirrhosis over 28 weeks of repeated injections, across 41 people. After 28 weeks of survodutide, liver fat, liver stiffness, liver volume, body weight and other liver and metabolic markers were generally lower in people with overweight or obesity, with or without Child-Pugh class A or B cirrhosis; the abstract gives no figures for these changes and names no placebo group.

  Lawitz EJ, Fraessdorf M, Neff GW, Schattenberg JM, Noureddin M, Alkhouri N, et al. Efficacy, tolerability and pharmacokinetics of survodutide, a glucagon/glucagon-like peptide-1 receptor dual agonist, in cirrhosis. J Hepatol. 2024 Nov;81(5):837-846. doi: 10.1016/j.jhep.2024.06.003. PMID: 38857788.

  C: Limited supportPrimary studyChecked 2026-09-29

• In SYNCHRONIZE-1, a 76-week phase 3 trial of 725 adults with obesity or overweight and at least one weight-related complication, without diabetes, and receiving lifestyle counseling, average body weight fell by 12.2% and 13.0% in the two survodutide groups, compared with 5.4% with placebo; by week 76, 72.6% and 71.9% of participants in those groups had lost at least 5% of their body weight, compared with 46.3% on placebo. Stomach and gut symptoms, typically mild to moderate, were the most common side effects, affecting 80.9% and 89.7% in the survodutide groups and 47.9% on placebo; no deaths were reported. Participants had an average age of 47.1 years and average BMI of 37.9, 40.6% were men, and the trial was funded by Boehringer Ingelheim and registered as NCT06066515.

  le Roux CW, Wharton S, Startseva E, Kloer IM, Hussain SA, Unseld A, et al. Survodutide Once Weekly for the Treatment of Adults with Obesity. N Engl J Med. 2026 Aug;395(8):776-787. doi: 10.1056/NEJMoa2600751. PMID: 42253238.

  A: High supportPrimary studyChecked 2026-09-29

• SYNCHRONIZE-MASLD (NCT06309992), a Boehringer Ingelheim phase 3 trial completed in December 2025, randomly assigned 218 adults with overweight or obesity and presumed or confirmed non-alcoholic steatohepatitis (NASH), without cirrhosis, to survodutide or placebo for 48 weeks, with diet and exercise counselling for all; the trial report describes 216 adults with obesity and at-risk MASLD (with signs of liver inflammation or scarring), recruited in the United States and Spain. Its two main measures were a fall in liver fat of at least 30 percent on MRI and change in body weight: 84.2 percent on survodutide and 24.3 percent on placebo met the liver-fat measure, or 68.5 and 28.6 percent in an analysis that also counts the effect of stopping treatment, while average body weight fell by 12.2 and 1.0 percent in the main efficacy analysis, or 8.7 and 1.4 percent in that other analysis. Liver stiffness, a marker of scarring, fell by 28.7 percent on survodutide and 9.2 percent on placebo when measured by FibroScan, but showed no difference between groups on MR elastography; the authors cite the short trial length and recruitment in only two countries as limitations. Stomach and gut side effects were most common on survodutide, mostly during dose increases and mostly mild to moderate, and led 19.9 percent of people on survodutide to stop treatment, compared with 4.3 percent on placebo; similar shares stopped for any reason (41.1 and 40.0 percent). The registry record shows no results posted and a certification or extension request to delay submitting results, first submitted on 24 April 2026, although the record prints 3 April 2026 as the date it was first posted.

  Kaplan LM, Startseva E, le Roux CW, Wharton S, Bozkurt B, Mazo DF, 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 Aug;32(8):2948-2958. doi: 10.1038/s41591-026-04479-3. PMID: 42252333.

  B: Moderate supportPrimary studyChecked 2026-09-29

• LIVERAGE (NCT06632444), sponsored by Boehringer Ingelheim, is a phase 3, randomized, double-blind, placebo-controlled trial of survodutide in adults living with obesity who have MASH with moderate or advanced liver scarring (fibrosis stage F2 to F3, without cirrhosis), planned for about 1,800 people. Its first part assesses by liver biopsy at week 52 whether MASH resolves without worsening scarring and whether scarring improves by at least one stage without worsening MASH; its second part follows participants for up to 7 years for progression to cirrhosis, death, liver transplant, or other serious liver events. ClinicalTrials.gov lists the study as recruiting, with main results estimated for 27 December 2031 and no results posted as of the record’s 17 September 2026 update.

  ClinicalTrials.gov, NCT06632444. LIVERAGE™: A Study to Test Whether Survodutide Helps People With a Liver Disease Called NASH/MASH Who Have Moderate or Advanced Liver Fibrosis. Sponsor: Boehringer Ingelheim.

  A: High supportclinical-trialChecked 2026-09-29

• A phase 3 trial sponsored by Boehringer Ingelheim, NCT07754461, began in August 2026 to test whether survodutide lowers blood sugar in adults with type 2 diabetes and a body mass index of 23 or more, compared with placebo over 56 weeks. Its main measure is the change in HbA1c, a marker of average blood sugar, at week 41; about 600 people are planned, it is recruiting, and no results are posted. The trial has three parts based on participants’ existing treatment: diet and physical activity alone, diabetes tablets, or basal insulin with or without tablets; in each part, two dose levels of survodutide are compared with placebo at sites listed in Australia, Canada, India, New Zealand, Puerto Rico and the United States.

  ClinicalTrials.gov, NCT07754461. A Study to Test Whether Survodutide Helps People With Type 2 Diabetes Control Their Blood Sugar. Sponsor: Boehringer Ingelheim.

  A: High supportclinical-trialChecked 2026-09-29

• Whether survodutide raises the energy people burn is being tested in NCT06745284, an open-label phase 1 study sponsored by Boehringer Ingelheim in 64 adults aged 18 to 65 with obesity, randomly assigned to survodutide or semaglutide. It measures sleeping metabolic rate, and fat burning during sleep, in a whole-room calorimeter at the first visit where a participant has lost at least 10 percent of body weight. It began in March 2025, is active but not recruiting, and has no results posted.

  ClinicalTrials.gov, NCT06745284. A Study to Test Whether Survodutide Improves How the Body Uses Energy and Breaks Down Fat in People With Obesity. Sponsor: Boehringer Ingelheim.

  A: High supportclinical-trialChecked 2026-09-29

• The European Medicines Agency’s page for survodutide’s paediatric investigation plan, EMEA-002942-PIP02-20-M02, lists decision P/0259/2024 of 16 August 2024 for the treatment of obesity with a solution for injection in a pre-filled syringe given under the skin, shows the decision document as first published on 7 July 2025, and records that no compliance check has been done on the plan.

  European Medicines Agency, Paediatric investigation plan EMEA-002942-PIP02-20-M02

  A: High supportRegulatoryChecked 2026-09-29

• The PubChem chemical database lists survodutide as compound 168429725, with the molecular formula C192H289N47O61 and a computed molecular weight of 4232.

  PubChem, Survodutide, CID 168429725

  A: High supportPrimary studyChecked 2026-09-29

• The US FDA Global Substance Registration System records survodutide (UNII 2ALA66NS64) as a synthetic peptide hormone with a 29-amino-acid chain and a six-amino-acid glycine-and-serine linker, joined by an amide bond to the side chain of lysine at position 24; the chain’s second building block is 1-aminocyclobutanecarboxylic acid, shown as X in the sequence, the linker carries an 18-carbon fatty diacid attached through gamma-glutamic acid, and the chain ends in an amide. The FDA record lists survodutide as a mimetic of human oxyntomodulin. Two public records give different molecular weights: the FDA record lists an estimated 3300 daltons, while PubChem computes 4232 for the same molecular formula, C192H289N47O61; the difference is reported as printed, not resolved.

  FDA Global Substance Registration System, Survodutide, UNII 2ALA66NS64

  A: High supportRegulatoryChecked 2026-09-29

• On 24 August 2026, the US FDA issued a warning letter to an online company after reviewing its website in July 2026, stating that a product it listed as survodutide, along with eight other products, was an unapproved new drug under the Federal Food, Drug, and Cosmetic Act, and that no approved application was in effect for it. The letter stated that labels marking the products “for laboratory, research, and analytical use” and “not intended for human or veterinary use” did not change this finding, because website evidence established that they were intended to be drugs for human use; it also said the products were especially concerning for public health because injectable drug products can pose risks of serious harm by being delivered directly into the body, sometimes into the bloodstream, and bypassing some of the body’s key defences against toxins and microorganisms.

  FDA, Warning Letter, NuScience Peptides LLC, 733652, August 24, 2026

  A: High supportRegulatoryChecked 2026-09-29

• A 2025 meta-analysis of six randomised trials involving 1,272 adults, with searches through July 2025, found that survodutide lowered HbA1c by 0.66 percentage points, body weight by 6.7 kg, and waist size by 7.09 cm more than placebo; effects on weight and waist size were larger in higher-dose subgroups and with treatment longer than 16 weeks. Survodutide was associated with a higher risk than placebo of stopping treatment because of adverse events, most commonly stomach and gut events, while serious adverse events were not significantly more frequent. The authors said larger, longer, multicentre, high-quality randomised trials in more diverse populations are needed to confirm the results.

  Xiao YJ, Yu S, Zhang YL, Chen J, Liu YQ, Liu XL, et al. Efficacy and safety of survodutide on glycemic control and weight loss in adults: A systematic review and meta-analysis. Diabetes Obes Metab. 2025 Dec;27(12):7062-7074. doi: 10.1111/dom.70105. PMID: 40922121.

  B: Moderate supportMeta-analysisChecked 2026-09-29

• A 2025 meta-analysis of four randomized trials of survodutide for obesity, searched through May 2024, found greater loss of starting body weight with survodutide than placebo (standardized mean difference −1.5); the abstract gave no figure in kilograms or percent. Overall adverse events did not differ significantly between groups (risk ratio 1.18, P = 0.08), while diarrhea was more common with survodutide (risk ratio 1.89, 95 percent interval 1.2 to 2.97). The abstract prints P < 0.00001 alongside the diarrhea interval; this appears inconsistent with the interval and is reported as printed. The abstract describes survodutide as a new GLP-1 agonist and does not mention its action at the glucagon receptor.

  Awad AA, Abdrabou Abouelmagd A, Mohammed F, Elettreby AM, Mahmoud Marey M, Aldemerdash MA, et al. Evaluating the efficacy and safety of survodutide for obesity: a systematic review and meta-analysis of randomized controlled trials. Proc (Bayl Univ Med Cent). 2025;38(4):514-522. doi: 10.1080/08998280.2025.2480512. PMID: 40557198.

  C: Limited supportMeta-analysisChecked 2026-09-29

• A 2024 meta-analysis of randomised controlled trials, searched to August 2024 and pooling 18 treatment arms with 1,029 people, found that injected survodutide lowered body weight by 8.33 kg, body mass index by 4.03 and waist size by 6.33 cm more than control. Results varied very widely between studies (I² of 99.6% for weight and 99.5% for waist), which the abstract does not discuss; the abstract also does not say how many trials the arms came from. In the same meta-analysis, subgroup analyses and meta-regression linked treatment longer than 16 weeks and higher doses to larger reductions in weight and waist size.

  Wan H, Xu N, Wang L, Liu Y, Fatahi S, Sohouli MH, et al. Effect of survodutide, a glucagon and GLP-1 receptor dual agonist, on weight loss: a meta-analysis of randomized controlled trials. Diabetol Metab Syndr. 2024 Nov 6;16(1):264. doi: 10.1186/s13098-024-01501-x. PMID: 39508238.

  C: Limited supportMeta-analysisChecked 2026-09-29

• In post hoc analyses of two phase 2 trials, survodutide raised HOMA-beta, a blood-test estimate of beta-cell function, and lowered HOMA-IR, an estimate of insulin resistance, glucagon and fasting blood sugar, compared with placebo, in a 16-week trial of 413 adults with type 2 diabetes taking metformin; fasting insulin, C-peptide and HMW adiponectin did not change significantly. In a 46-week trial of 387 adults with overweight or obesity and normal blood sugar, it did not significantly change HOMA-beta, but lowered HOMA-IR, glucagon, C-peptide, fasting insulin and fasting blood sugar, and raised HMW adiponectin, compared with placebo. Across the two trials, weight change explained the largest share of changes in fasting insulin and HOMA-IR, but not the other changes; the authors interpreted this as metabolic benefit beyond weight loss, while noting that it is unknown whether beta-cell improvements last after treatment stops. The analysis was funded by Boehringer Ingelheim, and five of its six authors are company employees.

  Ekinci EI, Maldonado SG, Unseld A, Martinez JA, Hennige AM, Schoelch C. Dual Glucagon and GLP-1 Receptor Agonist Survodutide Improves Biomarkers of Beta-Cell Function and Insulin Sensitivity in People With Type 2 Diabetes or Living With Overweight/Obesity. Diabetes Obes Metab. 2026 Sep;28(9):8242-8253. doi: 10.1111/dom.70861. PMID: 42331726.

  C: Limited supportPrimary studyChecked 2026-09-29

• In diet-induced obese mice, survodutide alone lowered body weight by 17%, compared with 22% when combined with experimental drug BI 1820237, which acts on the NPY2 receptor; the combined reduction was significantly larger, while BI 1820237 alone did not significantly lower body weight. An analysis across a range of dose combinations found that BI 1820237 increased survodutide’s weight-lowering effect by 265%, which the authors describe as synergy between the NPY2 receptor and the glucagon and GLP-1 receptors; the study was funded by Boehringer Ingelheim and reported no results in people.

  Augustin R, Oldenburger A, Baader-Pagler T, Zimmermann T, Borghardt J, Hecksher-Sørensen J, et al. Novel NPY2R agonist BI 1820237 provides synergistic anti-obesity efficacy when combined with the GCGR/GLP-1R dual agonist survodutide. Mol Metab. 2025 Sep;99:102205. doi: 10.1016/j.molmet.2025.102205. PMID: 40619099.

  C: Limited supportPrimary studyChecked 2026-09-29

• In cell assays reported in a 2026 conference abstract, not a full paper, by Boehringer Ingelheim scientists, survodutide activated the GLP-1 and glucagon receptors with about the same potency as the body’s own hormones when albumin was absent. Adding human serum albumin, the main protein in blood, made survodutide about eight times more potent at GLP-1R than at GCGR; a version without its fatty acid chain kept the same potency, and the authors attributed the shift to that chain. At GLP-1R, survodutide and the version without its fatty acid chain reached a maximal response consistent with natural GLP-1, while at GCGR survodutide recruited less beta-arrestin (54%) and caused less receptor internalisation (81%) than glucagon, which the authors interpreted as biased agonism that may lower receptor desensitisation and prolong its GCGR effects.

  Berger B, Schuler M, Haebel P, Klein T, Augustin R. 1220-OR: Survodutide: Differentiated GLP-1R and Glucagon Receptor (GCGR) Pharmacology Compared with Endogenous Ligands via Time-Resolved Assays. Diabetes. 2026 Jun;75(Supplement_1). doi: 10.2337/db26-1220-OR.

  C: Limited supportPrimary studyChecked 2026-09-29

• In a 2026 conference poster, male diet-induced obese mice housed at 28°C, a warmer temperature chosen to avoid cold stress, lost 27% of body weight with survodutide and 18% with semaglutide over 4 weeks, relative to mice given an inactive injection (8 mice per group); fat and lean mass fell similarly with both treatments, and muscle weight and grip strength did not differ. Survodutide raised energy expenditure, mainly in the second week, while food intake was suppressed to a similar degree with both treatments; the authors attributed the brief rise to glucagon receptor-driven heat production and fuel burning in the liver, and said cooler standard housing would mask it. Compared with mice given an inactive injection, blood levels of some amino acids, including tyrosine and serine, fell only with survodutide.

  Pereira M, Rist W, Hamilton B, Klein T. 2565-P: Survodutide Induces Superior Weight Loss and Energy Expenditure Compared with Semaglutide in DIO Mice Housed at Thermoneutrality. Diabetes. 2026 Jun;75(Supplement_1). doi: 10.2337/db26-2565-P.

  C: Limited supportPrimary studyChecked 2026-09-29

• A 2024 preprint that has not been peer reviewed reports that BI 456908, a compound structurally related to but not the same as survodutide, produced more weight loss than semaglutide by engaging glucagon receptors in the liver, without harming glucose control, and that these receptors are critical for the clearance of fats from the blood and liver stimulated by BI 456908. Its abstract does not specify whether the work was done in animals or cells.

  Long F, Klug M, Challa TD, Efthymiou V, Wolfrum C, Horvath C. Hepatic GCGR is required for the superior weight loss effects of a structurally related analogue of the dual GCGR/GLP1R agonist survodutide. bioRxiv. 2024 Sep 13. doi: 10.1101/2024.09.09.611134.

  C: Limited supportPrimary studyChecked 2026-09-29

• NCT05202353, a Boehringer Ingelheim phase 1 study in 29 adults with obesity, uses PET and MRI scans with radioactive tracers to measure what share of glucagon receptors in the liver, and of GLP-1 receptors in the pancreas, survodutide occupies after 17 weeks of treatment, compared with semaglutide. First registered in January 2022, it started in November 2024, is active but not recruiting, and has no results posted.

  ClinicalTrials.gov, NCT05202353. A Study in People With Obesity to Test the Effects of BI 456906 Compared With Semaglutide on Glucagon Receptor Activity in the Liver. Sponsor: Boehringer Ingelheim.

  A: High supportclinical-trialChecked 2026-09-29

• NCT06352424, a completed Boehringer Ingelheim phase 1 crossover study, gave 23 otherwise healthy adults aged 40 to 60 with overweight or obesity single doses of survodutide, the experimental NPY2 receptor drug BI 1820237, both together, or placebo, and used functional MRI to measure brain responses to food pictures and food preferences while fasting. It finished in February 2025 and has no results posted.

  ClinicalTrials.gov, NCT06352424. A Study in People With Overweight or Obesity to Test How BI 1820237, BI 456906, or a Combination of Both Affects Brain Activity. Sponsor: Boehringer Ingelheim.

  A: High supportclinical-trialChecked 2026-09-29

The studies that matter

• New England Journal of Medicine, SYNCHRONIZE-12026

  In a randomized phase 3 obesity trial, mean body-weight change was -12.2 percent and -13.0 percent in the two survodutide groups versus -5.4 percent with placebo. Gastrointestinal adverse events occurred in 80.9 percent and 89.7 percent versus 47.9 percent. The trial used placebo, was sponsor-led, and did not establish long-term safety.

  B: Moderate support

• The Lancet Diabetes and Endocrinology, phase 2 obesity trial2024

  Mean body-weight change ranged from -6.2 percent to -14.9 percent across survodutide groups versus -2.8 percent with placebo. Adverse events and low completion limit the result.

  B: Moderate support

• New England Journal of Medicine, phase 2 MASH trial2024

  MASH improvement without worsening fibrosis occurred in 47 percent, 62 percent, and 43 percent of the survodutide groups versus 14 percent with placebo. The fibrosis endpoint was less conclusive.

  B: Moderate support

• Nature Medicine, SYNCHRONIZE-MASLD2026

  The randomized phase 3 report found more liver-fat reduction and weight reduction with survodutide than placebo, but no between-group difference in liver stiffness. Gastrointestinal discontinuation was higher with survodutide.

  B: Moderate support