Survodutide

What is survodutide?

Survodutide is a glucagon-derived peptide, administered subcutaneously once weekly, that stimulates the glucagon receptor and the glucagon-like peptide-1 (GLP-1) receptor together. ^[2] GLP-1 receptor stimulation lowers weight mainly by reducing food intake; glucagon receptor stimulation also reduces food intake and increases fat breakdown (lipolysis) in the liver. According to the SYNCHRONIZE-2 article, survodutide’s potency at the GLP-1 receptor is about eight times that at the glucagon receptor. ^[4] The importance of this ratio is seen in an example cited in the phase 2 MASH article: the development of another dual agonist acting on glucagon and GLP-1 receptors in a different ratio was stopped because of dose-dependent heart rate increase, a decrease in reticulocyte count, and an increase in inflammation markers. ^[2]

In this respect it differs from semaglutide and liraglutide, which act only on the GLP-1 receptor, and from tirzepatide, which acts on GIP and GLP-1 receptors. For the investigational drug acting on three receptors together: Retatrutide; for the investigational drug targeting the amylin pathway: Cagrilintide. All the phase 2 and phase 3 trials named below were funded by the manufacturer, and company employees were among their authors. ^{[1] [2] [3] [5]}

Is survodutide approved? What is its status in Türkiye?

United States: The FDA’s page on unapproved GLP-1 drugs (content current as of October 1, 2026) states that it has warned companies illegally selling unapproved drugs containing semaglutide, tirzepatide, retatrutide, survodutide, or mazdutide by mislabeling them as “for research purposes” or “not for human use.” According to the FDA, these products were sold directly to consumers with dosing instructions; the agency asks that these products, whose quality is unknown and which may be harmful, not be purchased. ^[10] The published phase 3 articles on survodutide describe the molecule as “investigational.” ^[3]

Türkiye: No product containing survodutide appears on the TİTCK (Turkish Medicines and Medical Devices Agency) Licensed Human Medicinal Products List dated October 16, 2026. ^[11] Two provisions of the legislation are directly relevant:

• Article 3 of Law No. 1262 on Pharmaceutical and Medicinal Preparations (İspençiyari ve Tıbbi Müstahzarlar Kanunu) requires Ministry permission before domestically produced medicinal preparations are marketed and before those produced abroad are imported. ^[12]
• Article 24 of Law No. 6197 on Pharmacists and Pharmacies (Eczacılar ve Eczaneler Hakkında Kanun) stipulates that medicines cannot be sold on the internet or through any other electronic medium. ^[13]

Sport: The WADA 2026 Prohibited List does not name survodutide. However, class S0 always prohibits every pharmacological substance that does not appear in another section of the list and is not approved by any governmental health authority for human therapeutic use (for example, drugs in clinical development). ^[14] As long as survodutide has not received approval, it falls within the scope of this definition.

What did the phase 2 obesity trial show?

In a phase 2 dose-finding trial in 12 countries that enrolled 387 adults without diabetes and with BMI ≥27, participants received one of four survodutide doses or placebo for 46 weeks. In the analysis by dose assigned at randomization, weight change was −6.2% at the lowest dose, −14.9% at the highest dose, and −2.8% with placebo. The proportion completing the 46-week treatment was only 60.4% (61% with survodutide, 60% with placebo). Adverse events occurred in 91% of those receiving survodutide and 75% of those receiving placebo; they were mostly gastrointestinal (75% versus 42%). ^[1]

What did the phase 3 SYNCHRONIZE trials find?

The two phase 3 trials lasted 76 weeks and applied lifestyle counseling to all groups. In both, the primary analysis is the treatment-regimen estimand (intention-to-treat approach), which includes stopping the drug, use of prohibited obesity drugs, and the extended dose-escalation period. The efficacy estimand reported second rests on the assumption that everyone adhered to treatment and received no other obesity treatment. ^{[3] [4]} Below, the two target doses are referred to only as “low” and “high.”

In SYNCHRONIZE-1, 91.3% of participants completed the trial, but the proportion still using the drug or placebo at week 76 was 63.4%. The authors note that the high proportion of those who stopped the drug is most likely the main reason for the gap between the two estimands. Dose flexibility was initially limited to weeks 16–32, and a participant who missed three doses had to stop treatment; by the time a protocol amendment in February 2025 allowed restarting, most participants had passed three-quarters of the treatment period. In addition, although the protocol prohibited other obesity drugs, 16.5% of the placebo group (2.5% and 3.7% in the survodutide groups) reported using another GLP-1-acting drug while the trial was ongoing; this occurred mostly after they had stopped the trial drug. ^[3]

In SYNCHRONIZE-2, the baseline mean HbA1c was 7.4%; in the intention-to-treat analysis, HbA1c fell by 0.9 points at the low dose, 0.8 at the high dose, and 0.2 with placebo. The proportion still using the drug or placebo at week 76 was 66.2%. ^[4] Weight loss was markedly smaller than in people without diabetes. In both trials the comparison group is placebo; there is no direct comparison with another obesity drug. ^[3]

Fatty liver and MASH

The fat-breaking effect of glucagon in the liver has also made survodutide a candidate for metabolic dysfunction-associated steatohepatitis (MASH). ^[2]

• Phase 2 MASH (NEJM, 2024): 293 adults with biopsy-confirmed MASH and stage F1–F3 fibrosis were followed for 48 weeks. MASH improvement without worsening of fibrosis (primary endpoint) occurred in 47%, 62%, and 43% in the three dose groups and 14% with placebo. Improvement of at least one stage in fibrosis was 34%, 36%, and 34% versus 22%; these secondary results were not corrected for multiple comparisons and, according to the authors, should not be used to draw definitive treatment effects. The liver enzyme ALT fell at week 48 by up to 38.5 units per liter with survodutide and 5.7 units with placebo. ^[2]
• SYNCHRONIZE-1 MRI subgroup: In 25 participants per group at 76 weeks, with the high dose liver fat fell by 63.1% (24.5% with placebo) and visceral fat by 34.0% (11.8% with placebo); lean body volume fell by 9.8% (2.9% with placebo). ^[3]
• SYNCHRONIZE-MASLD (Nat Med, 2026): In 216 adults with obesity and at-risk fatty liver (US and Spain), a reduction of at least 30% in liver fat at 48 weeks occurred in 68.5% with survodutide and 28.6% with placebo in the intention-to-treat analysis, and in 84.2% versus 24.3% by the efficacy estimand. Weight change in the intention-to-treat analysis was −8.7% versus −1.4%. Discontinuation was similar in both arms (41.1% and 40.0%); discontinuation because of gastrointestinal events was 19.9% versus 4.3%. The primary endpoint is liver fat measured by MRI; the authors note the short duration and participation limited to two countries as limitations. ^[5]
• Cirrhosis (J Hepatol, 2024): In an open-label, non-randomized phase 1 trial, blood levels of a single dose were similar in people with cirrhosis and healthy people. In the 28-week multiple-dose cohort (41 people), drug-related adverse events were 82.4% in those without cirrhosis and 87.5% in those with cirrhosis; liver fat, liver stiffness, and weight generally decreased. ^[6]

These findings rest on intermediate endpoints such as liver fat, tissue score, and blood tests; the effect on events such as development of cirrhosis, liver failure, or transplant has not yet been shown. The phase 3 LIVERAGE trial in people with MASH and moderate or advanced fibrosis continues to enroll; the estimated primary completion date in the registry is 2031. ^[9]

Side effects and safety signals

• Gastrointestinal complaints: In SYNCHRONIZE-1, these occurred in 80.9% at the low dose, 89.7% at the high dose, and 47.9% with placebo; nausea was 61.0% and 64.9% versus 17.4%, and vomiting 40.7% and 44.6% versus 6.2%. The events were mostly during the dose-escalation period and mild to moderate in severity; discontinuation because of gastrointestinal events was 17.8% and 20.2% versus 2.9%. ^[3]
• Heart rate: At week 76, heart rate rose by 3.2–3.5 beats per minute in the survodutide groups and fell by 0.4 beats with placebo; no marked prolongation of the QT interval was seen. In SYNCHRONIZE-2 the increase was 2.7–2.9 beats. ^{[3] [4]}
• Low blood pressure, fainting, and sensory disturbance: In SYNCHRONIZE-1, hypotension including syncope was 7.4% at the high dose, 2.1% at the low dose, and 1.7% with placebo; skin sensory disturbance (dysesthesia) was reported in 3.7% and 2.5% versus 0.8%. Gallstones were also more frequent with survodutide (1.2% and 2.1% versus 0.4%). ^[3]
• Liver events: In SYNCHRONIZE-1, liver-related events were 5.4% and 4.1% in the survodutide groups and 5.8% with placebo; in SYNCHRONIZE-MASLD, no board-adjudicated drug-induced liver injury was seen in the survodutide group. ^{[3] [5]}
• Hypoglycemia in type 2 diabetes: In SYNCHRONIZE-2, hypoglycemia occurred in 8.0% and 9.2% of the survodutide groups and 4.0% with placebo; the only person with severe (level 3) hypoglycemia was using a sulfonylurea. ^[4]

Is the effect on cardiovascular risk known?

Not yet. In SYNCHRONIZE-1, no board-adjudicated major cardiovascular event occurred in the survodutide groups and one stroke occurred in the placebo group; in SYNCHRONIZE-2, two events (one myocardial infarction, one stroke) occurred in the low-dose group. ^{[3] [4]} These numbers are too small to interpret because they come from trials not designed to measure events. The SYNCHRONIZE-CVOT trial, which measures five-component major adverse cardiovascular events as the primary endpoint in adults with overweight and cardiovascular disease, chronic kidney disease, or multiple risk factors, has been designed. ^[7] According to the registry page, the trial has been completed with 5,531 participants (primary completion June 2026); its results have not yet been published in a peer-reviewed journal. ^[8]

Evidence table: claim, population, and limits

Limits of this guide

This page summarizes published peer-reviewed trials on survodutide, trial registries, and statements of regulatory bodies. It contains no dosing, administration, storage, or sourcing information and does not recommend use under any circumstances; the dose groups in the trials are referred to only as low and high. The trial results were obtained in adults selected by entry criteria and under physician monitoring within a protocol. ^[3] If a licensing process is completed, the product information may contain warnings and limits different from the trial results on this page.