Peptide education
Survodutide
BI 456906
Survodutide, also known as BI 456906, is an investigational peptide that activates glucagon and GLP-1 receptors. It has been studied in obesity, including in people with and without type 2 diabetes, and in metabolic liver disease. No matching product was found in the FDA drug database or the EMA's EEA authorized-product dataset.
Published phase 3 trials found greater weight reduction with survodutide than placebo in adults with obesity or qualifying overweight, both with and without type 2 diabetes. Gastrointestinal events were common.
Overview
Quick answer
SYNCHRONIZE-MASLD measured liver fat by MRI in people with at-risk metabolic fatty liver disease. A separate phase 2 trial used biopsies to assess inflammatory liver disease, called MASH. Lower liver fat on MRI is not the same outcome as improvement in liver tissue.
What does survodutide do?
It is designed to activate glucagon and GLP-1 receptors. Clinical trials have measured body weight, liver fat, liver tissue changes, and safety in different groups of adults.
What happened in the weight trials?
At 76 weeks, both phase 3 studies found greater average weight reduction than placebo. SYNCHRONIZE-1 enrolled people without diabetes; SYNCHRONIZE-2 enrolled people with type 2 diabetes.
What happened in liver studies?
A phase 2 biopsy trial found more improvement in MASH without worsening fibrosis than placebo. The phase 3 SYNCHRONIZE-MASLD trial measured MRI liver fat and weight, not biopsy-defined MASH resolution.
Is it approved?
No matching approved product was found in the FDA drug database or the EMA's EEA authorized-product dataset. Development designations from regulators do not authorize marketing.
What side effects were reported?
Nausea, vomiting, diarrhea, and constipation were common. Rates and discontinuations differed across the individual trials and doses.
Evidence
Evidence snapshot
SYNCHRONIZE-1 reported average 76-week weight changes of -12.2% and -13.0% in the two survodutide groups versus -5.4% with placebo, using the treatment-regimen analysis.
SYNCHRONIZE-2 reported average weight changes of -8.2% and -9.8% in the two active groups versus -3.9% with placebo at 76 weeks, using the same type of analysis.
SYNCHRONIZE-MASLD assessed liver fat by MRI; the separate phase 2 MASH trial measured changes in biopsy findings.
Searches of FDA drug data and the EMA's EEA authorized-product data found no matching product. The developer describes the drug as investigational.
FDA has warned about unapproved products, including survodutide, sold under research-use labels.
Claims
Common claims vs evidence
| Claim | Human evidence | Verdict |
|---|---|---|
| Survodutide reduced weight in phase 3 trials. | Two placebo-controlled studies reported greater average weight reduction at week 76 in adults with obesity or qualifying overweight, with and without type 2 diabetes. | Supported in the studied populations. Results depend on the trial, treatment group, and statistical analysis. |
| SYNCHRONIZE-MASLD proved that MASH resolved. | The phase 3 study measured the proportion with at least a 30% relative reduction in liver fat by MRI and measured weight change. The phase 2 MASH study assessed liver tissue by biopsy. | MRI liver-fat reduction and biopsy-defined MASH improvement are different findings from different studies. |
| Survodutide is better than approved weight-loss drugs. | The phase 3 weight trials compared survodutide with placebo. They did not establish superiority over another weight-loss medicine. | Numbers from separate trials are not a reliable head-to-head comparison. |
| A research-use vial is the study drug. | Clinical outcomes came from controlled trial material. FDA has separately warned about unapproved products including survodutide marketed under research-use labels. | A product label does not establish identity, strength, or sterility. |
Bottom line
Main takeaway
Survodutide is a drug candidate being studied for weight and metabolic liver disease. No matching product was found in the FDA or EEA authorized-product datasets searched.
Check whether a figure describes people with diabetes, people without diabetes, or people with at-risk MASLD. The studies have different populations, endpoints, and durations.
The two phase 3 weight trials report treatment-regimen analyses. The phase 3 liver study reports both treatment-regimen and efficacy analyses; its MRI endpoint should remain separate from the phase 2 biopsy endpoint.
Identity
What it is
Survodutide is an investigational peptide licensed to Boehringer Ingelheim by Zealand Pharma. It is designed to activate glucagon and GLP-1 receptors and has been studied as a weekly subcutaneous injection.
Metabolic dysfunction-associated steatotic liver disease, or MASLD, means liver fat in the setting of metabolic dysfunction. MASH is an inflammatory form with liver cell injury; fibrosis refers to liver scarring.
The published liver studies differ in who entered them and what they measured. SYNCHRONIZE-MASLD included people with at-risk MASLD identified through noninvasive tests or prior biopsy. The phase 2 MASH trial required biopsy-confirmed MASH and F1 to F3 fibrosis.
Use context
Routes, doses, and cycle patterns
The following regimens describe the dose groups and follow-up periods used in controlled studies. Each trial had its own eligibility criteria, escalation schedule, and clinical monitoring.
Human studies and product labels
SYNCHRONIZE-1
- Purpose
- Weight change in adults without diabetes
- Context
- Phase 3, obesity or overweight with a qualifying complication
- Route
- Subcutaneous
- Amount
- Adjusted up to 3.6 mg or 6.0 mg in active study arms
- Frequency
- Once weekly
- Duration
- 76 weeks
Doses were increased toward the assigned target with flexibility for tolerability. The study compared each active arm with placebo alongside lifestyle counseling.
SYNCHRONIZE-2
- Purpose
- Weight change in adults with type 2 diabetes
- Context
- Phase 3, body mass index of at least 27
- Route
- Subcutaneous
- Amount
- 3.6 mg or 6.0 mg target in active study arms
- Frequency
- Once weekly
- Duration
- 76 weeks
Doses were increased toward the assigned target with flexibility for tolerability. Weight and blood glucose outcomes were assessed in a population with type 2 diabetes.
SYNCHRONIZE-MASLD
- Purpose
- MRI liver-fat and body-weight change
- Context
- Phase 3, at-risk MASLD and obesity or qualifying overweight
- Route
- Subcutaneous
- Amount
- 6.0 mg target in the active arm after escalation
- Frequency
- Once weekly
- Duration
- 48 weeks
The trial included a 24-week escalation phase. Dose reduction was allowed, so the assigned target was not necessarily every participant's maintained dose.
Phase 2 MASH biopsy study
- Purpose
- Histologic MASH improvement without worsening fibrosis
- Context
- Adults with biopsy-confirmed MASH and F1 to F3 fibrosis
- Route
- Subcutaneous
- Amount
- 2.4 mg, 4.8 mg, or 6.0 mg in active study arms
- Frequency
- Once weekly
- Duration
- 48 weeks
The trial included a 24-week escalation phase followed by a maintenance phase.
What varies
- The weight studies enrolled different groups depending on whether participants had type 2 diabetes.
- MRI liver fat and biopsy findings are distinct outcomes.
- Treatment-regimen and efficacy estimands answer different questions about treatment interruptions and other events.
Research
Research evidence
Two published phase 3 trials report weight outcomes in adults with and without type 2 diabetes. A separate phase 3 study measured MRI liver fat in at-risk MASLD. Biopsy-based MASH improvement was studied in phase 2; phase 3 studies in MASH are also underway.
| Study / evidence area | Population | Design | Product context | Main outcome | Limitations | Weight |
|---|---|---|---|---|---|---|
| SYNCHRONIZE-1 | 725 adults with obesity or qualifying overweight, without diabetes | Randomized, double-blind, placebo-controlled phase 3 trial | Controlled investigational study drug | At 76 weeks, mean weight change was -12.2% with 3.6 mg and -13.0% with 6.0 mg versus -5.4% with placebo, using the treatment-regimen estimand. | Adverse events led to treatment discontinuation in 23.7% and 24.8% of the active groups versus 5.4% with placebo. A placebo comparison does not establish superiority over other treatments or fully characterize long-term safety. | Peer-reviewed phase 3 weight evidence |
| SYNCHRONIZE-2 | 752 adults with overweight or obesity and type 2 diabetes | Randomized, double-blind, placebo-controlled phase 3 trial | Controlled investigational study drug | At 76 weeks, mean weight change was -8.2% with 3.6 mg and -9.8% with 6.0 mg versus -3.9% with placebo, using the treatment-regimen estimand. Average HbA1c also fell in both active groups. | The study population differs from SYNCHRONIZE-1; numerical differences between trials do not establish why the outcomes differed. | Peer-reviewed phase 3 weight and diabetes evidence |
| SYNCHRONIZE-MASLD | 218 randomized adults with obesity or qualifying overweight and at-risk MASLD; 216 received treatment | Randomized, double-blind, placebo-controlled phase 3 trial | Controlled investigational study drug | At week 48, the estimated proportions with at least a 30% relative reduction in MRI liver fat were 68.5% with survodutide and 28.6% with placebo by the treatment-regimen estimand. Estimated mean weight changes were -8.7% and -1.4%, respectively. | The primary liver endpoint was imaging-based, not MASH resolution on biopsy. The 48-week trial recruited in the United States and Spain. | Peer-reviewed phase 3 imaging evidence |
| Phase 2 MASH and fibrosis trial | 293 treated adults with biopsy-confirmed MASH and F1 to F3 fibrosis | Randomized, double-blind, placebo-controlled phase 2 trial | Controlled investigational study drug | In the planned-treatment analysis, MASH improvement without worsening fibrosis occurred in 47%, 62%, and 43% of the 2.4 mg, 4.8 mg, and 6.0 mg groups versus 14% with placebo at 48 weeks. | The trial did not establish long-term clinical liver outcomes. Rapid escalation was associated with gastrointestinal discontinuations. | Peer-reviewed phase 2 biopsy evidence |
| LIVERAGE and LIVERAGE-Cirrhosis | Adults with MASH and noncirrhotic F2 or F3 fibrosis, or compensated MASH cirrhosis | Separate registered phase 3 trials | ClinicalTrials.gov trial registrations | Both trials are recruiting; their efficacy results are not yet available. | Trial registrations describe planned outcomes, not completed findings. | Ongoing research |
Cautions
Safety and unknowns
- In SYNCHRONIZE-1, gastrointestinal adverse events occurred in 80.9% and 89.7% of participants in the 3.6 mg and 6.0 mg groups, versus 47.9% with placebo. Events were typically mild or moderate. Adverse events led to treatment discontinuation in 23.7% and 24.8% versus 5.4% with placebo; gastrointestinal events led to discontinuation in 17.8% and 20.2% versus 2.9% of participants, respectively.
- In the phase 2 MASH trial, nausea occurred in 66% of participants across the survodutide groups versus 23% with placebo. Adverse events led to treatment discontinuation in 20% versus 3%, respectively; many occurred during rapid dose escalation.
- In SYNCHRONIZE-MASLD, gastrointestinal events led to treatment discontinuation in 19.9% with survodutide versus 4.3% with placebo. Long-term outcomes and uncommon adverse effects remain under study.
Product quality
Product identity and quality
FDA has warned about unapproved products including survodutide sold under research-use labels. Trial findings do not establish the contents or safety of a product from a different source.
Identity and strength
A product label alone cannot establish the substance or amount present.
Sterility and handling
Contamination, storage, and transport can affect an injectable product independently of clinical evidence.
Oversight
The trials included screening, monitoring, and adverse-event reporting.
Mechanism
How it is proposed to work
Survodutide is designed to activate glucagon and GLP-1 receptors. The combination is being studied for effects on appetite, body weight, and liver metabolism.
GLP-1 signaling is associated with appetite and glucose regulation.
Glucagon receptor signaling is being studied for its role in energy and liver metabolism.
Receptor activity does not by itself show superiority over another medicine.
FAQ
Common questions
Is survodutide approved in the United States or European Economic Area?
No matching FDA-approved product or EEA authorized product was found in the databases searched. The developer describes survodutide as investigational; FDA and EMA development designations are not marketing approval.
Did SYNCHRONIZE-MASLD prove MASH resolved?
No. Its primary liver endpoint measured change in MRI liver fat. A separate phase 2 trial measured histologic MASH improvement in people with biopsy-confirmed disease.
Details
Technical details
Sources
References
- 1.
PubMed. Survodutide once weekly for the treatment of adults with obesity
doi:10.1056/NEJMoa2600751 PMID:42253238 NCT06066515
Peer-reviewed phase 3 SYNCHRONIZE-1 trial in adults without diabetes; outcomes use the treatment-regimen estimand.
- 2.
PubMed. Survodutide once weekly in adults with obesity and type 2 diabetes
doi:10.1056/NEJMoa2607219 PMID:42820639 NCT06066528
Peer-reviewed phase 3 SYNCHRONIZE-2 trial in adults with type 2 diabetes; weight outcomes use the treatment-regimen estimand.
- 3.
Obesity. Survodutide for treatment of obesity: rationale and design of SYNCHRONIZE-1 and SYNCHRONIZE-2
doi:10.1002/oby.24184
Trial design describes dose escalation and flexibility for the two phase 3 weight studies.
- 4.
Nature Medicine. Survodutide in adults with obesity and metabolic dysfunction-associated steatotic liver disease: SYNCHRONIZE-MASLD
doi:10.1038/s41591-026-04479-3 PMID:42252333 NCT06309992
Peer-reviewed phase 3 trial of MRI-measured liver fat and body weight, not a histologic MASH resolution trial.
- 5.
PubMed. A phase 2 randomized trial of survodutide in MASH and fibrosis
doi:10.1056/NEJMoa2401755 PMID:38847460 NCT04771273
Peer-reviewed phase 2 trial in biopsy-confirmed MASH with fibrosis stages F1 through F3.
- 6.
ClinicalTrials.gov. LIVERAGE phase 3 study of survodutide in MASH and fibrosis
NCT06632444
Registry describes a recruiting trial in MASH with moderate or advanced fibrosis, excluding cirrhosis.
- 7.
ClinicalTrials.gov. LIVERAGE-Cirrhosis phase 3 study of survodutide in MASH cirrhosis
NCT06632457
Registry describes a separate recruiting trial in MASH-related cirrhosis.
- 8.
Zealand Pharma. Survodutide development pipeline
Developer description of investigational status, development designations, and ongoing MASH studies.
- 9.
FDA. FDA concerns with unapproved GLP-1 drugs used for weight loss
FDA describes warnings to firms selling unapproved products including survodutide under research-use labels.
- 10.
FDA. openFDA Drugs@FDA database
Search of active ingredient names returned no survodutide match; database results are not a substitute for a regulator decision.
- 11.
EMA. EMA Article 57 authorized product data
The periodically updated EEA authorized-product dataset was searched for survodutide and BI 456906; no match was found in the available snapshot.