Glossary · PeptideU · 7 min read

What Is Survodutide? Definition and What Research Reports

What Is Survodutide? Definition and What Research Reports
The short answer

Survodutide is an investigational, once-weekly peptide that activates two receptors at once: the glucagon receptor (GCGR) and the GLP-1 receptor (GLP-1R). It was developed under the code BI 456906 and has been studied in obesity, type 2 diabetes, metabolic dysfunction-associated steatohepatitis (MASH) and cirrhosis. Published phase 2 trials reported dose-dependent reductions in body weight and HbA1c and improvements in liver histology, with gastrointestinal events most commonly reported. Phase 3 SYNCHRONIZE trials have been published. This page is definitional and educational only.

Plain-language definition

Survodutide is an investigational injectable peptide designed to switch on two different hormone receptors in the body at the same time — the receptor for GLP-1 (a gut hormone involved in appetite and blood-sugar control) and the receptor for glucagon (a pancreatic hormone involved in liver metabolism and energy expenditure). Because it acts at both, it is described in the literature as a dual glucagon/GLP-1 receptor agonist. It was created as a once-weekly candidate for obesity and related metabolic conditions and has been tested in human trials, but it is a research compound rather than an everyday clinical product. This page is for educational purposes only and is not medical advice; consult a licensed physician about any medical or metabolic condition.

Survodutide in biochemical and regulatory terms

Survodutide is a synthetic, lipidated (fatty-acid–modified) peptide analogue engineered from the glucagon/GLP-1 peptide family. The fatty-acid chain promotes albumin binding, which extends the circulating half-life enough to support once-weekly subcutaneous administration in trials. The molecule first appeared in the literature under its development code BI 456906; the discovery and preclinical pharmacology paper described it as a novel GCGR/GLP-1R dual agonist with robust anti-obesity efficacy in preclinical models (PMID 36356832). A later pharmacological profiling paper described the biomarker work and receptor-balance considerations that researchers used for clinical candidate selection (PMID 38560764).

In regulatory terms, survodutide is an investigational agent. It has not been characterised in the literature cited here as an approved medicine; instead, it appears as a study drug in randomised phase 2 and phase 3 clinical trials, including the SYNCHRONIZE programme in obesity (PMID 39495965). Anything sold or labelled outside that clinical-trial or licensed-pharmacy context is not the material described in these publications and has no published characterisation.

Why a glucagon component was added

GLP-1 receptor agonism is associated with reduced appetite and improved glycaemic control. Adding glucagon receptor agonism was intended, per the preclinical literature, to engage hepatic and energy-expenditure pathways alongside appetite reduction (PMID 36356832). A review of survodutide in MASH framed this dual mechanism as an attempt to bridge hepatic and systemic metabolic dysfunction rather than to treat weight alone (PMID 39663847).

What the published literature reports

Type 2 diabetes (phase 2)

A randomised clinical trial published in Diabetologia examined dose–response effects on HbA1c and body weight in people with type 2 diabetes, comparing several survodutide dose levels against placebo and open-label semaglutide. The study reported dose-dependent reductions in both HbA1c and body weight over the treatment period (PMID 38095657).

Obesity (phase 2)

A randomised, double-blind, placebo-controlled dose-finding phase 2 trial in adults with obesity evaluated ascending weekly dose levels up to 4.8 mg over 46 weeks. Researchers reported dose-dependent mean body-weight reductions that were substantially greater than placebo, with the largest reductions at the highest dose groups (PMID 38330987).

MASH, MASLD and cirrhosis

A phase 2 randomised trial published in the New England Journal of Medicine studied survodutide in adults with biopsy-confirmed MASH and fibrosis over 48 weeks. The study reported that a higher proportion of participants receiving survodutide than placebo had histological improvement in MASH without worsening of fibrosis (PMID 38847460). A separate study examined efficacy, tolerability and pharmacokinetics in people with cirrhosis, an important question for any agent with hepatic mechanisms (PMID 38857788). In 2026, the SYNCHRONIZE-MASLD randomised, double-blind, placebo-controlled phase 3 trial reported outcomes in adults with obesity and metabolic dysfunction-associated steatotic liver disease (PMID 42252333).

Phase 3 programme

Design papers described SYNCHRONIZE-1 and SYNCHRONIZE-2 as randomised phase 3 trials in obesity (PMID 39495965), with a companion publication reporting baseline characteristics of SYNCHRONIZE-1 participants (PMID 41187967). A cardiovascular outcomes trial, SYNCHRONIZE-CVOT, was described separately in terms of rationale and design (PMID 39453356). Phase 3 results for once-weekly survodutide in adults with obesity were subsequently published in the New England Journal of Medicine (PMID 42253238).

Setting studiedDesignWhat researchers reported
Preclinical modelsDiscovery and pharmacology (PMID 36356832)GCGR/GLP-1R dual agonism with anti-obesity efficacy in animal models
Type 2 diabetesRandomised phase 2 vs placebo and open-label semaglutide (PMID 38095657)Dose-dependent HbA1c and body-weight reduction
ObesityPhase 2 dose-finding, 46 weeks (PMID 38330987)Dose-dependent body-weight reduction vs placebo
MASH with fibrosisPhase 2, 48 weeks (PMID 38847460)Higher rates of histological MASH improvement without fibrosis worsening vs placebo
CirrhosisPharmacokinetics and tolerability study (PMID 38857788)Pharmacokinetic and tolerability characterisation in hepatic impairment
Obesity (phase 3)SYNCHRONIZE trials (PMID 42253238, PMID 42252333)Once-weekly dosing evaluated in obesity and in obesity with MASLD

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Adverse Events in Trials: What Studies Report

Across the published trials, gastrointestinal events were the most frequently reported adverse events. In the phase 2 obesity dose-finding trial, researchers reported nausea, vomiting and diarrhoea as the most common adverse events, occurring more often during dose escalation and more often at higher dose levels than with placebo (PMID 38330987). The phase 2 MASH trial similarly reported gastrointestinal adverse events as the most common with survodutide compared with placebo (PMID 38847460). The type 2 diabetes trial also described tolerability in the context of dose escalation across its dose groups (PMID 38095657), and a dedicated study assessed tolerability in participants with cirrhosis (PMID 38857788). Adverse-event profiles observed in controlled trials cannot be assumed to apply outside of medically supervised study conditions.

How the term is used — and where it is misused

In the scientific literature, "survodutide" refers specifically to the clinical candidate formerly designated BI 456906, evaluated in company-sponsored randomised trials. Common points of confusion include:

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References

Frequently asked questions

What does "dual glucagon/GLP-1 receptor agonist" mean?

It means one molecule activates two receptors: the glucagon receptor and the GLP-1 receptor. The discovery paper described survodutide (BI 456906) as a GCGR/GLP-1R dual agonist with anti-obesity efficacy in preclinical models (PMID 36356832), and a profiling paper described the receptor-balance and biomarker work researchers used when selecting the clinical candidate (PMID 38560764).

Is survodutide the same as semaglutide or tirzepatide?

No. Survodutide acts at the glucagon and GLP-1 receptors. Semaglutide acts at the GLP-1 receptor alone and was used as an open-label comparator in a phase 2 type 2 diabetes trial that reported dose-dependent HbA1c and body-weight reductions with survodutide (PMID 38095657). Other multi-agonists combine different receptor sets, so the terms are not interchangeable.

What did phase 2 obesity research report?

A randomised, double-blind, placebo-controlled dose-finding phase 2 trial evaluated weekly survodutide doses up to 4.8 mg over 46 weeks in adults with obesity. Researchers reported dose-dependent mean body-weight reductions that exceeded placebo, with the greatest reductions in the higher-dose groups (PMID 38330987). These were controlled trial findings, not statements about outcomes outside trial conditions.

What has been published about survodutide and liver disease?

A phase 2 trial in adults with MASH and fibrosis reported that more participants receiving survodutide than placebo had histological improvement in MASH without worsening fibrosis over 48 weeks (PMID 38847460). A separate study characterised pharmacokinetics and tolerability in cirrhosis (PMID 38857788), and a phase 3 trial, SYNCHRONIZE-MASLD, reported results in obesity with MASLD (PMID 42252333).

Which adverse events did the trials report most often?

Gastrointestinal events were the most commonly reported. The phase 2 obesity trial reported nausea, vomiting and diarrhoea more frequently than placebo, particularly during dose escalation (PMID 38330987), and the phase 2 MASH trial also reported gastrointestinal events as most common with survodutide (PMID 38847460). Trial tolerability data reflect supervised study settings only.

Is survodutide an approved medicine?

In the literature cited here it appears as an investigational agent studied in randomised trials rather than as an approved product. Design papers described the phase 3 SYNCHRONIZE-1 and -2 obesity trials (PMID 39495965) and a cardiovascular outcomes trial (PMID 39453356), and phase 3 obesity results were later published (PMID 42253238). This page is educational and is not medical advice.

Why is survodutide sometimes called BI 456906?

BI 456906 was the development code used before the international nonproprietary name was assigned. The 2022 discovery and preclinical pharmacology paper published under that code described the molecule as a novel GCGR/GLP-1R dual agonist (PMID 36356832). Later clinical publications, including phase 2 and phase 3 reports, used the name survodutide for the same compound (PMID 38330987).

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References

  1. PMID 36356832
  2. PMID 38560764
  3. PMID 38095657
  4. PMID 38330987
  5. PMID 38847460
  6. PMID 38857788
  7. PMID 39453356
  8. PMID 39495965
  9. PMID 41187967
  10. PMID 42253238
  11. PMID 42252333
  12. PMID 39663847
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18+ · Educational purposes only
This page summarises published research for education — it is not medical advice, and nothing here is a recommendation to use, purchase, or dose any substance. Study parameters described are what researchers reported, not instructions. Consult a qualified clinician before any health decision.
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