Survodutide

Origin and structure

Survodutide was developed under the code BI 456906. It was co-invented by the Danish company Zealand Pharma and Boehringer Ingelheim; under their licensing agreement Boehringer funds all research, development and commercialisation. The idea behind it comes from oxyntomodulin, a natural gut hormone that weakly activates both the GLP-1 and the glucagon receptor and that reduces body weight in people by lowering food intake and raising energy expenditure.

Chemically it is a 29-amino-acid peptide built on the sequence of human glucagon, with changes along the chain that set how strongly it activates each receptor. An unnatural amino acid (1-aminocyclobutane-1-carboxylic acid) at position 2 protects it from the enzyme DPP-4, the end of the chain is amidated, and a glycine–serine linker at position 24 carries a C18 fatty diacid that binds to albumin in the blood. That albumin binding is what makes a once-weekly injection possible. The molecular formula is C192H289N47O61, a mass of about 4.2 kDa.

How it is thought to work

Survodutide acts on two receptors at once. Through the GLP-1 receptor it works like semaglutide: it lowers appetite via the brain, slows stomach emptying and raises insulin release when blood sugar is high. Through the glucagon receptor, found mainly in the liver, it is meant to increase the burning of fat in the liver and the body's energy expenditure. Glucagon on its own raises blood sugar, so the balance matters: in cell assays run in human plasma, survodutide was about eight times more potent at the GLP-1 receptor than at the glucagon receptor.

The energy-expenditure part rests mainly on mouse studies, in which survodutide caused more weight loss than the highest effective dose of semaglutide, through both lower food intake and higher energy expenditure. Whether it raises energy expenditure in people is still being measured in a small phase 1 study (NCT06745284). In people, the large fall in liver fat fits with activity at the glucagon receptor in the liver.

Is survodutide approved?

No. As of October 2026 survodutide is not approved as a medicine anywhere.

In the EU it was not on the EMA's list of medicines under evaluation (data extracted 5 October 2026), so no marketing-authorisation application had been validated. In the Netherlands it is therefore not a registered medicine. Sites in the Netherlands do take part in the trials: SYNCHRONIZE-1 and -2, the cardiovascular trial SYNCHRONIZE-CVOT and the MASH trials LIVERAGE and LIVERAGE-Cirrhosis.

In the US the FDA granted survodutide Breakthrough Therapy designation for MASH in 2024, a status meant to speed up the development of drugs that may be a substantial improvement on existing treatment. It is not an approval.

Research-grade survodutide, the lyophilised peptide sold for laboratory use, is not the trial medicine. It is not made under a medicines licence and may not be used in people.

What the research shows

Survodutide has been through phase 2 trials in type 2 diabetes, obesity and MASH, and a phase 3 programme with two strands: SYNCHRONIZE in obesity and LIVERAGE in MASH. All of these trials were funded by Boehringer Ingelheim. Phase 3 weight results are reported two ways: the treatment-regimen estimand counts everyone, including people who stopped or switched to other obesity drugs, while the efficacy estimand estimates the effect if everyone had stayed on treatment. The main results:

• Phase 2, type 2 diabetes (Diabetologia 2024): 413 participants for 16 weeks; HbA1c fell by up to 1.71 percentage points and body weight by up to 8.7%, against 5.3% on open-label semaglutide up to 1 mg.
• Phase 2, obesity (Lancet Diabetes Endocrinol 2024): 387 adults without diabetes for 46 weeks; −14.9% on 4.8 mg against −2.8% on placebo, analysed by assigned dose. Only about 60% in both the survodutide and placebo groups completed treatment, and gastrointestinal adverse events affected 75% on survodutide against 42% on placebo.
• Phase 2, MASH (NEJM 2024): 293 adults with biopsy-confirmed MASH and fibrosis stage F1 to F3, 48 weeks; MASH improved without worsening of fibrosis in 47%, 62% and 43% on 2.4, 4.8 and 6.0 mg against 14% on placebo, and fibrosis improved by at least one stage in 34% to 36% against 22%.
• SYNCHRONIZE-1 (NEJM 2026): 725 adults with obesity and no diabetes, 76 weeks; −12.2% on 3.6 mg and −13.0% on 6.0 mg against −5.4% on placebo (treatment regimen), or −15.3% and −16.6% against −3.2% (efficacy). At least 5% weight loss: 72.6% and 71.9% against 46.3%.
• SYNCHRONIZE-2 (NEJM 2026): 752 adults with obesity and type 2 diabetes, 76 weeks; −8.2% and −9.8% against −3.9% on placebo, and HbA1c fell by 0.9 and 0.8 percentage points from 7.4%, against 0.2 on placebo.
• SYNCHRONIZE-MASLD (Nat Med 2026): 216 adults with obesity and at-risk fatty liver disease, 6.0 mg for 48 weeks; liver fat fell by at least 30% in 84.2% against 24.3% on placebo (68.5% against 28.6% by treatment regimen), and body weight by 12.2% against 1.0% (8.7% against 1.4% by treatment regimen). Liver stiffness on FibroScan fell by 28.7% against 9.2%, but on MR elastography, where baseline values were already low, it did not differ from placebo.
• Still running or unpublished: SYNCHRONIZE-CVOT, a cardiovascular safety trial in 5,531 people that finished in mid-2026 according to its registry entry, with no results in a journal yet; LIVERAGE (about 1,800 people with MASH and F2 to F3 fibrosis, biopsy results at 52 weeks and outcomes over up to 7 years) and LIVERAGE-Cirrhosis (about 1,590 people with compensated MASH cirrhosis).

Side effects and warnings

As with other drugs that act on the GLP-1 receptor, most side effects are gastrointestinal: nausea, vomiting, diarrhoea and constipation, mostly mild to moderate and concentrated in the weeks when the dose is being raised. They were very common. In SYNCHRONIZE-1, 80.9% on 3.6 mg and 89.7% on 6.0 mg had gastrointestinal events, against 47.9% on placebo. In SYNCHRONIZE-MASLD, 56.2% had nausea and 42.5% vomiting on 6.0 mg, against 14.3% and 7.1% on placebo, and 23.3% stopped treatment because of adverse events, against 10.0%.

Heart rate goes up a little: in SYNCHRONIZE-MASLD it rose by 3.6 beats per minute at week 52, against 0.8 on placebo, a rise the authors note is also seen with other GLP-1-based drugs, without clinically relevant QT prolongation. In that trial there were no confirmed cases of drug-induced liver injury, acute pancreatitis, or pancreatic or thyroid cancer on survodutide, and in the phase 2 MASH trial serious adverse events were about as common as on placebo (8% against 7%).

Long-term data are missing. The published trials ran for at most 76 weeks, the cardiovascular safety trial has not been published, and rare risks known from GLP-1 medicines, such as pancreatitis and gallbladder problems, will only become clear from larger and longer studies.

Survodutide versus semaglutide, tirzepatide and mazdutide

No phase 3 trial has compared survodutide head to head with another obesity drug. The only direct comparison is the 16-week phase 2 diabetes trial, in which survodutide at 1.8 mg or more per week gave more weight loss than open-label semaglutide up to 1 mg (up to −8.7% against −5.3%), and the 0.9 mg dose lowered HbA1c about as much as semaglutide.

Across separate trials, survodutide's weight loss is in the range of semaglutide 2.4 mg and below tirzepatide, but the trials differ in population, length and how dropouts are counted. SYNCHRONIZE-1 also had an unusually large placebo effect, partly because more than 16% of the placebo group started other GLP-1-based medication during the trial. On current evidence its distinctive effect is in the liver, where the glucagon component is expected to add a direct effect on liver fat; whether that prevents progression to cirrhosis and other liver events is what LIVERAGE is testing.

Mazdutide, a similar GLP-1/glucagon dual agonist, has published phase 3 results (GLORY-1) and is approved in China for chronic weight management, so the class itself is no longer purely experimental. Survodutide's own phase 3 work in liver disease, LIVERAGE and LIVERAGE-Cirrhosis, is still running.

Frequently asked questions

Is survodutide approved?

No. As of October 2026 no regulator has approved it. In the EU no marketing application was under evaluation at the EMA in October 2026. In the US it has had Breakthrough Therapy designation for MASH since 2024, which speeds up development but is not an approval.

How much weight did people lose on survodutide?

In SYNCHRONIZE-1, adults with obesity but without diabetes lost 13.0% of their body weight on 6.0 mg over 76 weeks, against 5.4% on placebo; calculated as if everyone had stayed on treatment, 16.6% against 3.2%. People with type 2 diabetes lost less: 9.8% against 3.9% in SYNCHRONIZE-2.

Is survodutide stronger than Wegovy or Mounjaro?

Not on the evidence so far. No phase 3 trial has compared them directly, and across separate trials its weight loss is in the range of semaglutide 2.4 mg (Wegovy) and below tirzepatide (Mounjaro). Its possible advantage is in the liver, which the LIVERAGE trials are testing.

Is survodutide legal in the Netherlands?

It is not a registered medicine in the Netherlands or anywhere else, so it may not be sold, advertised or supplied for use in people. Buying and selling it as research material is a different status, which our guide on research-use-only products in the Netherlands explains.

Is survodutide banned in sport?

Yes, at all times. It is not named on the WADA Prohibited List, but class S0 covers any pharmacological substance that the list does not otherwise address and that has no approval for human therapeutic use, including drugs still in clinical development. Approved GLP-1 medicines such as semaglutide are permitted; survodutide is not, because it is unapproved. In the Netherlands the Dopingautoriteit applies the same list.

Storage and handling

Store according to product-label instructions and batch handling notes. Lyophilized research peptides are commonly kept dry, protected from light, and handled with clean laboratory technique.

References

Checked against these sources on 28 October 2026.