Survodutide (research code BI 456906) is a laboratory-made peptide that activates the glucagon receptor and the GLP-1 receptor — the same one semaglutide acts on — at the same time. It is being developed by Boehringer Ingelheim with two diseases in mind at once: obesity and steatotic liver disease (MASH, formerly NASH). The first phase 3 results appeared in 2026 — in the “New England Journal of Medicine” and “Nature Medicine” — so the human evidence is solid, although newer and less extensive than for semaglutide or tirzepatide. Survodutide is not an approved medicine in any country. Its hallmark in trials is a long, months-long dose escalation and a high proportion of people who stop treatment because of gastrointestinal complaints. Below we set out what the publications show.
What survodutide is
Survodutide belongs to the group of “dual GLP-1 and glucagon agonists”. The idea comes from nature: after a meal the gut releases oxyntomodulin — a hormone that activates both of these receptors and lowers body weight in humans by increasing energy expenditure and reducing food intake. The natural hormone, however, acts for minutes. Survodutide is an “acylated” peptide: it has an 18-carbon fatty acid attached that prolongs its presence in the blood enough for one injection a week to suffice (Zimmermann et al., 2022). In clinical trials it is compared with placebo and with semaglutide; the target doses in phase 3 are 3.6 and 6.0 mg weekly (Wharton et al., 2025).
How it works — GLP-1 plus glucagon
The “GLP-1” part suppresses appetite, slows stomach emptying and improves insulin secretion. The “glucagon” part is meant to add what GLP-1 does not do: in the liver, glucagon increases fat breakdown and raises energy expenditure. In mouse studies (Zimmermann et al., 2022) survodutide lowered body weight more than maximally effective doses of semaglutide, and the authors attribute this advantage precisely to the combination of eating less with burning more. Activation of the glucagon receptor was confirmed in the liver (increased expression of the enzyme NNMT) and in the blood (changes in amino acids and the hormone FGF21). The price of this mechanism is the effect on the heart: glucagon speeds up the heart rate, and indeed in a 16-week trial in people with diabetes heart rate rose by 2.3–7.3 beats per minute depending on the dose (semaglutide: 5.9; placebo: 1.7), and in the year-long SYNCHRONIZE-MASLD trial by 3.6 against 0.8 on placebo (Blüher et al., 2024; Kaplan et al., 2026).
What was studied in animals — where in the brain it acts
A 2026 paper (Zimmermann et al.) examined how survodutide reaches the brain. The fluorescently labelled peptide accumulated in the circumventricular organs — parts of the brain outside the blood–brain barrier that “read” hormones from the blood — and in neighbouring nuclei of the hypothalamus and brainstem, but it did not penetrate uniformly into the whole brain. Interestingly, the glucagon receptor was barely detectable in these regions (area postrema, arcuate nucleus), whereas the GLP-1 receptor was present. The conclusion: appetite suppression by survodutide depends on the GLP-1 receptor, whereas a glucagon agonist on its own did not activate satiety centres and did not reduce eating, yet still lowered body weight — that is, it works through burning, not through appetite. This is consistent with the division of roles between the two receptors, but these are mouse studies.
Human data — obesity
The phase 2 trial (le Roux et al., 2024) enrolled 387 people with a BMI of at least 27 and without diabetes at 43 centres in 12 countries. It lasted 46 weeks: 20 weeks of gradual dose escalation and 26 weeks at the target dose (0.6, 2.4, 3.6 or 4.8 mg weekly). In the analysis by planned dose, body weight fell by 6.2%, 12.5%, 13.2% and 14.9% against 2.8% on placebo. One caveat: only 60.4% of participants completed the trial. The phase 3 SYNCHRONIZE-1 trial (le Roux et al., 2026) enrolled 725 adults without diabetes (mean BMI 37.9, weight 108.8 kg), randomised to survodutide 3.6 mg, 6.0 mg or placebo for 76 weeks; the protocol allowed the dose escalation to be prolonged. In the primary analysis — which also counts people who stopped treatment or turned to other medicines — body weight fell by 12.2% (3.6 mg) and 13.0% (6.0 mg) against 5.4% on placebo; at least 5% of body weight was lost by 72.6%, 71.9% and 46.3% of participants. The high placebo result and the modest difference between doses set this trial apart from phase 2. Separate phase 3 trials in people with diabetes (SYNCHRONIZE-2, NCT06066528, 755 people) and of cardiovascular safety (SYNCHRONIZE-CVOT, NCT06077864, 5,531 people) were completed in 2025–2026, but their results have not yet been published.
Human data — the liver
The most distinctive line of survodutide research is steatohepatitis (MASH). In phase 2 (Sanyal et al., 2024) 293 people with biopsy-confirmed MASH and fibrosis stage F1–F3 received survodutide 2.4, 4.8 or 6.0 mg or placebo for 48 weeks. Improvement in MASH without worsening of fibrosis was found in 47%, 62% and 43% of those treated against 14% on placebo; a reduction in liver fat of at least 30% in 63%, 67% and 57% against 14%; and improvement in fibrosis by at least one stage in 34%, 36% and 34% against 22%. The signal for the inflammation itself is therefore clear; the signal for fibrosis is more modest. In the phase 3 SYNCHRONIZE-MASLD trial (Kaplan et al., 2026) 216 people with obesity and “at-risk” steatotic liver disease (signs of inflammation or fibrosis on non-invasive tests, or a biopsy) received survodutide 6.0 mg or placebo for 48 weeks. A reduction in liver fat of at least 30% (on MRI) was achieved by 84.2% of those treated against 24.3% on placebo in the analysis assuming the treatment was taken, and by 68.5% against 28.6% in the analysis counting everyone; body weight fell by 12.2% against 1.0% and by 8.7% against 1.4% respectively. The trial was run only in the USA and Spain. Large phase 3 biopsy trials in MASH (the LIVERAGE programme, NCT06632444, 1,800 people) will run until 2031.
Human data — type 2 diabetes
In a 16-week phase 2 trial (Blüher et al., 2024) 413 people with type 2 diabetes on metformin received six survodutide regimens, placebo or open-label semaglutide 1.0 mg. HbA1c fell by 0.91–1.71 percentage points depending on the dose, with a low dose of survodutide giving the same as semaglutide (−1.46 against −1.47); body weight fell by at most 8.7% (1.8 mg twice weekly) against 5.3% with semaglutide. Adverse events were reported by 77.8% of people on survodutide against 52.5% on placebo and 52.0% on semaglutide. A meta-analysis of six trials (Xiao et al., 2025; 1,272 people) gives overall −0.66 HbA1c points, −6.7 kg of body weight and −7.1 cm of waist circumference against placebo, but also significantly more discontinuations because of adverse events, without an increase in serious events.
Safety, tolerability and the limits of the evidence
Survodutide is not an approved medicine; the Drugs@FDA database lists no product containing it (as of September 2026). The main problem is tolerability. Gastrointestinal complaints were reported in SYNCHRONIZE-1 by 80.9% of people on 3.6 mg and 89.7% on 6.0 mg against 47.9% on placebo; in the phase 2 MASH trial 66% had nausea (placebo 23%), 49% diarrhoea (23%) and 41% vomiting (4%). In SYNCHRONIZE-MASLD 41.1% of people on survodutide and 40.0% on placebo stopped treatment, of whom 23.3% against 10.0% did so because of adverse events. That is why the trials use months-long dose escalation (20 weeks in the obesity phase 2, 24 weeks in the liver trials, flexible in phase 3) — the SYNCHRONIZE-MASLD authors state plainly that an overly rigid escalation scheme worsened tolerability. Added to this is the rise in heart rate. What is not known: the phase 3 results in diabetes, the effect on heart attacks and strokes, the durability of the effect after stopping, and safety beyond 76 weeks. All the trials were funded by Boehringer Ingelheim, and some of the authors are company employees. The data concern a pharmaceutical-grade medicine with supervised escalation — they do not carry over to products from the unregulated market. We deliberately give no methods of use and no doses.
The wider context — dual GLP-1 and glucagon agonists
Survodutide and mazdutide are two members of the same class; mazdutide is already approved in China, while survodutide awaits the results of the rest of its phase 3 programme. What separates them from tirzepatide is the second receptor (glucagon instead of GIP), and retatrutide combines all three. In the only trial with semaglutide (1.0 mg) as comparator, survodutide produced more weight loss, but at the cost of worse tolerability — the hallmark of the glucagon component. An overview of the whole group can be found in our text on GLP-1, GIP and glucagon peptides.
Summary
Survodutide is a once-weekly dual agonist of the glucagon and GLP-1 receptors, studied in parallel in obesity and in steatotic liver disease. In phase 3 it lowered body weight by 13.0% against 5.4% on placebo after 76 weeks (in the analysis counting all participants) and reduced liver fat by at least 30% in most of those treated; in phase 2 it improved MASH on biopsy, but the signal for fibrosis was modest. The popular figure of “16.6%” comes from a manufacturer's announcement and refers to the analysis assuming the treatment was taken, not from a peer-reviewed abstract. The price of the glucagon mechanism is frequent nausea and vomiting, months-long dose escalation, a high rate of treatment discontinuation and a rise in heart rate. The evidence is strong but fresh and incomplete — the compound remains unapproved.
Sources
- le Roux CW, Wharton S, Startseva E, et al.; SYNCHRONIZE-1 Investigators. Survodutide Once Weekly for the Treatment of Adults with Obesity. The New England Journal of Medicine. 2026;395(8):776–787. PMID: 42253238. DOI: 10.1056/NEJMoa2600751. pubmed.ncbi.nlm.nih.gov/42253238
- Kaplan LM, Startseva E, le Roux CW, et al.; SYNCHRONIZE-MASLD Investigators. Survodutide in adults with obesity and metabolic dysfunction-associated steatotic liver disease: SYNCHRONIZE-MASLD, a randomized, double-blind, placebo-controlled phase 3 trial. Nature Medicine. 2026;32(8):2948–2958. PMID: 42252333. DOI: 10.1038/s41591-026-04479-3. pubmed.ncbi.nlm.nih.gov/42252333
- le Roux CW, Steen O, Lucas KJ, Startseva E, Unseld A, Hennige AM. Glucagon and GLP-1 receptor dual agonist survodutide for obesity: a randomised, double-blind, placebo-controlled, dose-finding phase 2 trial. The Lancet Diabetes & Endocrinology. 2024;12(3):162–173. PMID: 38330987. DOI: 10.1016/S2213-8587(23)00356-X. pubmed.ncbi.nlm.nih.gov/38330987
- Sanyal AJ, Bedossa P, Fraessdorf M, et al.; 1404-0043 Trial Investigators. A Phase 2 Randomized Trial of Survodutide in MASH and Fibrosis. The New England Journal of Medicine. 2024;391(4):311–319. PMID: 38847460. DOI: 10.1056/NEJMoa2401755. pubmed.ncbi.nlm.nih.gov/38847460
- 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;67(3):470–482. PMID: 38095657. DOI: 10.1007/s00125-023-06053-9. pubmed.ncbi.nlm.nih.gov/38095657
- Xiao YJ, Yu S, Zhang YL, et al. Efficacy and safety of survodutide on glycemic control and weight loss in adults: A systematic review and meta-analysis. Diabetes, Obesity & Metabolism. 2025;27(12):7062–7074. PMID: 40922121. DOI: 10.1111/dom.70105. pubmed.ncbi.nlm.nih.gov/40922121
- Wharton S, le Roux CW, Kosiborod MN, 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. PMID: 39495965. DOI: 10.1002/oby.24184. pubmed.ncbi.nlm.nih.gov/39495965
- Zimmermann T, Thomas L, Baader-Pagler T, et al. BI 456906: Discovery and preclinical pharmacology of a novel GCGR/GLP-1R dual agonist with robust anti-obesity efficacy. Molecular Metabolism. 2022;66:101633. PMID: 36356832. DOI: 10.1016/j.molmet.2022.101633. pubmed.ncbi.nlm.nih.gov/36356832
- Zimmermann T, Bleymehl K, Haebel P, et al. Survodutide acts through circumventricular organs in the brain and activates neuronal regions associated with appetite regulation. Molecular Metabolism. 2026;105:102326. PMID: 41638399. DOI: 10.1016/j.molmet.2026.102326. pubmed.ncbi.nlm.nih.gov/41638399
For in-vitro laboratory research only. It is not a human medicine and is not for treatment.