Survodutide

What is survodutide?

Survodutide, also known by its code BI 456906, is an experimental once-weekly injectable drug developed by Boehringer Ingelheim in partnership with the Danish company Zealand Pharma. It activates two hormone receptors: GLP-1, the target of semaglutide, and glucagon. That combination sets it apart from tirzepatide, which pairs GLP-1 with GIP instead of glucagon.

Survodutide is being studied for obesity and, most prominently, for metabolic dysfunction-associated steatohepatitis (MASH), the inflammatory form of fatty liver disease that can lead to scarring, cirrhosis and liver cancer⁵. It has completed phase 2 trials in both areas and moved into phase 3⁶. It is not approved anywhere, and outside clinical trials it is available only through unregulated research-chemical sellers.

How survodutide works

GLP-1 is a gut hormone that reduces appetite, slows stomach emptying and helps control blood sugar. Glucagon is better known for raising blood sugar between meals, but it also tells the liver to burn fat and increases the energy the body uses. Survodutide combines both signals in one molecule. The GLP-1 side drives people to eat less and keeps blood sugar in check, while the glucagon side is meant to clear fat from the liver directly and add to weight loss. That liver effect is why its developers have focused heavily on fatty liver disease.

In precise terms, survodutide is a lipidated peptide agonist of the glucagon receptor (GCGR) and the GLP-1 receptor, with a half-life of around a week. Glucagon receptor activation in hepatocytes increases fatty acid oxidation and reduces lipogenesis, lowering liver fat beyond what weight loss alone would explain. Survodutide and retatrutide are the leading examples of drugs that pair glucagon and GLP-1 receptor activation³. Reviews of MASH drug development group these dual agonists with GLP-1 and GIP/GLP-1 drugs as incretin-based therapies with growing evidence in liver disease⁸.

What the research shows on survodutide

The strongest evidence is in MASH. In a 48-week phase 2 trial of 293 adults with biopsy-confirmed MASH and fibrosis stages F1 to F3, improvement in MASH without worsening fibrosis occurred in 47%, 62% and 43% of those on 2.4, 4.8 and 6.0 mg, compared with 14% on placebo¹. Fibrosis improved by at least one stage in about 34% to 36% on survodutide versus 22% on placebo, a secondary endpoint¹. Liver fat fell by at least 30% in 57% to 67% of those on survodutide, compared with 14% on placebo¹. The middle dose performed best on the main endpoint, so the highest dose was not automatically better. A 2025 network meta-analysis of MASH drugs ranked survodutide among the most effective agents for MASH resolution⁷.

In obesity, a 46-week phase 2 dose-finding trial in 387 adults without diabetes found mean weight changes of -6.2% to -14.9% across doses, compared with -2.8% on placebo⁴. A Bayesian network meta-analysis estimated that dual agonists as a group, pairing GLP-1 with either GIP or glucagon, produce mean weight loss similar to retatrutide and greater than GLP-1 drugs alone, with a more favorable balance of efficacy and side effects than retatrutide².

These results have important limits. Both main trials were phase 2, funded by Boehringer Ingelheim, and relatively short. In the obesity trial, only about 60% of participants completed the 46-week treatment period⁴. Cross-trial comparisons in network meta-analyses are not the same as head-to-head trials. Phase 3 outcomes in obesity and MASH, including longer-term liver outcomes, will determine whether survodutide reaches the market.

Studied for: Investigational MASH treatment, Obesity research.

Survodutide reference data

Survodutide dosage in published research

How survodutide is used in practice

Legitimately, survodutide is used only in clinical trials, where it is started at a low dose and escalated over weeks to reduce gastrointestinal side effects. In the phase 2 trials, escalation took 20 to 24 weeks⁴¹.

It is not available through doctors, telehealth services or compounding pharmacies. Some research-peptide websites sell products labeled as survodutide. These are unregulated, and their identity, purity, dose and sterility are unverified. Because the drug is long-acting, a mislabeled or contaminated product can cause problems lasting a week or more, and self-escalating without monitoring raises the risk of severe nausea, vomiting and dehydration.

Survodutide risks and side effects

Gastrointestinal side effects are common and appear more frequent than with GLP-1 drugs alone. In the MASH trial, nausea occurred in 66% of survodutide recipients versus 23% on placebo, diarrhea in 49% versus 23%, and vomiting in 41% versus 4%¹. In the obesity trial, gastrointestinal adverse events affected 75% of those on survodutide versus 42% on placebo⁴. Reviews identify tolerability as a major concern for this class in MASH⁸.

Glucagon receptor agonism can raise heart rate, and increases were seen in trials. As with other GLP-1-based drugs, potential risks include pancreatitis, gallbladder problems, dehydration-related kidney injury and slowed stomach emptying that affects oral medicines and anesthesia. People with a history of medullary thyroid cancer were excluded from trials. It should not be used in pregnancy. Like other drugs that produce large weight loss, it is likely to reduce muscle as well as fat, so protein intake and resistance exercise matter. Long-term safety, including effects of years of glucagon receptor activation, is unknown.

Reported side effects

Alternatives to survodutide

For MASH with moderate to advanced fibrosis, two drugs are FDA approved: resmetirom (Rezdiffra), a liver-directed thyroid hormone receptor agonist, and semaglutide (Wegovy). Network meta-analyses also show strong results for tirzepatide and several drugs still in development, such as pegozafermin⁷. Weight loss of around 10% through any means, along with limiting alcohol and managing diabetes, remains central to MASH care.

For obesity, approved options with far more data include semaglutide, tirzepatide and liraglutide, oral medicines such as phentermine-topiramate and naltrexone-bupropion, and metabolic and bariatric surgery.

Questions for a clinician

• What evidence applies to my situation, and at what level?
• What established alternatives should I consider first?
• What monitoring would be necessary, and how often?
• Can this be prescribed at all where I live, or only sold for research?