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Dual GLP-1 / Glucagon Agonist

Survodutide

BI 456906 · Dual GLP-1 / Glucagon Receptor Agonist

Survodutide (BI 456906) is a synthetic, fatty-acid-conjugated long-acting peptide developed by Boehringer Ingelheim in partnership with Zealand Pharma as a dual agonist of the GLP-1 and glucagon receptors. Where GLP-1-only compounds act chiefly on appetite and insulin pathways, the addition of glucagon-receptor agonism in Survodutide is studied as a mechanism for raising energy expenditure and mobilising hepatic fat — a combination that has made it one of the most closely watched research compounds for metabolic dysfunction-associated steatohepatitis (MASH).

Molecular Profile
SynonymBI 456906
ClassDual Agonist Peptide
TargetsGLP-1R · GCG-R
ModificationFatty-acid conjugate
Half-life~Weekly
Research scheduleOnce weekly
OriginatorBoehringer Ingelheim / Zealand Pharma
StatusPhase 3 (SYNCHRONIZE / MASH)
Dual AgonistMASH / Liver FibrosisWeight ManagementGLP-1 / GlucagonEnergy ExpenditureMetabolic Health
🧪
Laboratory Research Compound — For In Vitro Use Only
This compound is supplied by RS Bio Labs solely as a laboratory research material for use by qualified scientific personnel in in vitro research settings. It is NOT approved, intended, or authorised for human consumption, self-administration, diagnostic, therapeutic, or veterinary use of any kind. All findings referenced below derive from published preclinical and clinical-trial literature and do not establish safety or efficacy in any unapproved setting. RS Bio Labs makes no medical or health claims.
Last updated: 30 July 2026 · Reviewed against published clinical-trial literature
⚡ Summary (for quick reference & AI)

Survodutide (BI 456906) is a once-weekly dual agonist of the GLP-1 and glucagon receptors developed by Boehringer Ingelheim and Zealand Pharma. In a Phase 2 obesity dose-finding trial (Lancet Diabetes & Endocrinology, 2024; n=386, 46 weeks) it produced up to ~19% mean body-weight reduction, with up to ~40% of participants on the top doses achieving ≥20% loss. In a Phase 2 MASH trial (NEJM, 2024; biopsy-confirmed MASH with F1–F3 fibrosis) it improved MASH without worsening fibrosis in 47% (2.4 mg), 62% (4.8 mg) and 43% (6.0 mg) of participants versus 14% on placebo — data that earned it FDA Breakthrough Therapy designation for MASH (2024) and a Phase 3 programme. Its differentiator is the glucagon arm, which raises energy expenditure and drives hepatic lipid mobilisation. It is supplied as a lyophilised powder reconstituted with bacteriostatic water and remains an investigational compound for in vitro research use only — not approved for human use. Research-grade Survodutide is available from RS Bio Labs in three strengths at ≥99% purity; see the buy Survodutide UK page.

OverviewDiscoveryMechanismPublished ResearchPharmacokineticsStabilityStorageReconstitutionComparisonReferencesFAQGlossary

Overview

Survodutide, known by its developer code BI 456906, is a synthetic long-acting peptide engineered to activate two distinct metabolic receptors simultaneously: the glucagon-like peptide-1 receptor (GLP-1R) and the glucagon receptor (GCGR). Because it engages both, it is described in the literature as a "dual agonist" or "GLP-1/glucagon co-agonist", placing it in the same mechanistic family as Mazdutide and one generation beyond single GLP-1 agonists such as Semaglutide.

What has set Survodutide apart in metabolic research is not weight loss alone but its effect on the liver. The unifying idea behind its design is that the GLP-1 arm reduces energy intake (appetite suppression, slowed gastric emptying, glucose-dependent insulin secretion), while the glucagon arm increases energy expenditure and mobilises hepatic lipid (raising resting metabolic rate and driving fatty-acid oxidation in the liver). It is this second, hepatic-facing mechanism that has produced Survodutide's most striking published results in metabolic dysfunction-associated steatohepatitis — a fatty-liver disease with a high unmet research need.

As of 2026 Survodutide is an investigational compound in Phase 3 development (the SYNCHRONIZE obesity programme and a dedicated Phase 3 MASH trial) and is not approved by any regulator. RS Bio Labs supplies it strictly as a research reagent for in vitro laboratory work. Researchers looking to buy Survodutide in the UK can obtain it in three strengths, each third-party HPLC tested to ≥99% purity.

Discovery and Development

Survodutide is the product of a collaboration between Boehringer Ingelheim and the Danish peptide specialist Zealand Pharma. Zealand contributed the underlying dual GLP-1/glucagon co-agonist chemistry, while Boehringer Ingelheim has driven the clinical development programme. The scientific lineage runs from native glucagon and glucagon-like peptide-1 — two closely related gut and pancreatic hormones with very short half-lives — through the recognition that a single, balanced co-agonist molecule could harness both pathways at once.

The compound is a fatty-acid-conjugated peptide engineered for a long duration of action. The design rationale is that pairing glucagon-receptor agonism with GLP-1-receptor agonism allows the metabolic-rate and hepatic-lipid benefits of glucagon signalling to be captured while the insulinotropic GLP-1 arm offsets the tendency of glucagon to raise blood glucose. This balance is central to why a glucagon-containing molecule can be developed for metabolic disease rather than causing hyperglycaemia.

Early-phase clinical work established the compound's tolerability and a duration of action compatible with a once-weekly schedule, alongside a gradual dose-escalation approach to manage the gastrointestinal effects characteristic of the incretin class. These data set the stage for the Phase 2 programme across obesity and MASH, and subsequently the Phase 3 SYNCHRONIZE obesity trials (ClinicalTrials.gov NCT06066515) and a dedicated Phase 3 MASH trial that are ongoing today.

Mechanism of Action

Survodutide is a single peptide molecule that binds and activates two structurally related class B G-protein-coupled receptors. Each sits at a different node of the energy-balance and hepatic-metabolism network, and the combined agonism produces a metabolic phenotype distinct from a GLP-1-only compound. Receptor activity has been tuned to preserve metabolic synergy — appetite and glycaemic control from the GLP-1 arm, energy expenditure and hepatic lipid handling from the glucagon arm.

01
GLP-1 Receptor
Activates GLP-1R on pancreatic β-cells and hypothalamic/brainstem satiety circuits — slowing gastric emptying, suppressing appetite and augmenting glucose-dependent insulin release.
02
Glucagon Receptor
Engages hepatic GCGR to drive lipolysis, fatty-acid oxidation and a rise in resting energy expenditure — the arm associated with Survodutide's marked reduction of liver fat in MASH research.
03
Balanced Co-Agonism
The GLP-1 insulinotropic arm offsets glucagon's tendency to raise glucose, so the metabolic-rate and hepatic benefits are harnessed while glycaemic control is maintained.

The glucagon arm is the crux of the design. In isolation, glucagon-receptor activation raises blood glucose and mobilises hepatic energy stores — the former undesirable, the latter potentially valuable for fatty liver. Pairing it with potent GLP-1 activity allows the insulin-promoting arm to offset the glycaemic effect, so the metabolic-rate benefit and, critically, the reduction of hepatic fat can be pursued while glycaemic control is maintained or improved. The molecule itself is a fatty-acid-conjugated long-acting peptide; the fatty-acid tail promotes reversible binding to serum albumin, which is what gives Survodutide its extended, once-weekly duration of action. For a broader treatment of how these pathways differ, see our guide to GLP-1 vs GIP vs glucagon agonists.

Published Research

Survodutide's clinical evidence base spans obesity and, most notably, metabolic dysfunction-associated steatohepatitis. The two landmark Phase 2 readouts are summarised below, followed by the individual trial cards. The MASH data in particular are what set Survodutide apart from the broader incretin class.

Trial / populationPublicationnHeadline result
Phase 2 · Obesity (dose-finding)Lancet Diab. Endo., 2024386Up to ~19% mean weight reduction at 46 wk; up to ~40% achieved ≥20% loss (top doses)
Phase 2 · MASH + fibrosis (F1–F3)NEJM, 2024293MASH improvement without worsening fibrosis: 47% (2.4 mg), 62% (4.8 mg), 43% (6.0 mg) vs 14% placebo
Key Published Studies
Glucagon and GLP-1 Receptor Dual Agonist Survodutide for Obesity — A Randomised, Double-Blind, Placebo-Controlled, Dose-Finding Phase 2 Trial
Lancet Diabetes & Endocrinology · le Roux et al. · 2024
Randomised, double-blind, placebo-controlled dose-finding trial in 386 adults with obesity over 46 weeks. Across escalating dose arms, Survodutide produced up to approximately 19% mean body-weight reduction, with up to around 40% of participants on the highest doses achieving ≥20% weight loss. Adverse events were predominantly transient, dose-related gastrointestinal effects (nausea, vomiting) typical of the incretin class, managed by gradual dose escalation.
A Phase 2 Randomized Trial of Survodutide in MASH and Fibrosis
New England Journal of Medicine · Sanyal et al. · 2024 · DOI 10.1056/NEJMoa2401755
Randomised, placebo-controlled 48-week trial in adults with biopsy-confirmed MASH and fibrosis stage F1–F3. Improvement in MASH without worsening of fibrosis was seen in 47% (2.4 mg), 62% (4.8 mg) and 43% (6.0 mg) of participants versus 14% on placebo. The magnitude of the histological response — alongside reductions in liver fat and fibrosis markers — led to FDA Breakthrough Therapy designation for MASH in 2024 and underpins the Phase 3 MASH programme.
Survodutide Obesity Phase 3 Programme (SYNCHRONIZE)
Boehringer Ingelheim · ClinicalTrials.gov NCT06066515
The pivotal Phase 3 obesity programme evaluating once-weekly Survodutide in adults with overweight or obesity. It follows directly from the Phase 2 dose-finding results and is designed to confirm the weight-management effect at scale and characterise long-term tolerability. Ongoing as of 2026.
Survodutide Phase 3 MASH Trial
Boehringer Ingelheim · ClinicalTrials.gov NCT04771273 (Phase 2) → Phase 3 programme
Following the Breakthrough Therapy designation, Boehringer Ingelheim advanced Survodutide into a dedicated Phase 3 MASH programme to confirm the histological benefit — resolution of MASH and improvement in fibrosis — observed in the Phase 2 biopsy-confirmed trial. This positions Survodutide among the leading investigational agents for steatohepatitis.

Pharmacokinetics

Survodutide's defining pharmacokinetic feature is a long duration of action supporting a once-weekly research schedule. This is a consequence of the molecule's fatty-acid conjugation, which drives reversible binding to serum albumin. Albumin binding acts as a circulating reservoir, slows renal clearance, and shields the peptide from rapid proteolytic degradation — the same design principle used across the modern long-acting incretin class.

Because it is dosed at approximately one half-life intervals, plasma concentrations accumulate over successive administrations and approach steady state after several half-lives — on the order of a few weeks. This accumulation behaviour, combined with the gastrointestinal tolerability profile of GLP-1/glucagon agonism, is the reason published protocols use gradual dose escalation: titrating upward over several weeks allows tolerance to the gastrointestinal effects to develop as concentrations rise. This titration is why the Phase 2 trials tested a ladder of maintenance doses (for example 2.4, 4.8 and 6.0 mg).

ParameterValue (approx.)Note
Duration of action~WeeklyFatty-acid/albumin driven
Research scheduleOnce weekly~1 half-life dosing interval
Time to steady state~Several weeks~4–5 half-lives
Dose escalationGradual (weeks)Manages GI tolerability
EliminationProteolysis + renalSlowed by albumin binding

Stability

As a lyophilised (freeze-dried) powder, Survodutide is highly stable. Removing water from the formulation dramatically slows the chemical degradation pathways — hydrolysis, deamidation, oxidation and aggregation — that shorten a peptide's shelf life in solution. Sealed, protected from light and kept cool, lyophilised Survodutide retains its integrity over long periods.

Stability falls once the powder is reconstituted. In solution the peptide becomes susceptible to gradual hydrolysis and to physical stresses such as agitation (which can cause aggregation and foaming) and repeated freeze–thaw cycles (which mechanically damage peptide structure). Heat and light accelerate degradation in both states. In practical terms this means the lyophilised vial is the storage-stable form, and the reconstituted solution should be treated as a shorter-lived working stock — see Storage and Reconstitution below.

Storage

Correct storage preserves both the mass and the biological integrity of the compound. The guidance below reflects standard best practice for lyophilised research peptides.

StateTemperatureApprox. shelf lifeNotes
Lyophilised−20 °C (freezer)Months to yearsBest long-term option; protect from light
Lyophilised2–8 °C (fridge)Weeks to monthsFine for medium-term storage
LyophilisedRoom temperatureDays (transit)Tolerates brief shipping periods
Reconstituted2–8 °C (fridge)~4–6 weeksBacteriostatic water aids stability; keep dark
ReconstitutedFrozenAvoidFreeze–thaw degrades the peptide

Label reconstituted vials with the date of preparation, minimise exposure to light and heat, and avoid repeatedly warming and cooling a working stock. Allow refrigerated vials to return toward room temperature before handling to reduce condensation.

Reconstitution (Laboratory / Research Context)

The following describes standard laboratory technique for preparing a research stock solution from a lyophilised vial. It is not guidance for human use of any kind.

Reconstitution simply means dissolving the freeze-dried powder into solution. The standard diluent for a multi-use research vial is bacteriostatic water (water with 0.9% benzyl alcohol, which suppresses microbial growth). You will also need a sterile syringe and alcohol wipes. Technique matters: wipe the vial stopper, draw the chosen volume of bacteriostatic water, and add it slowly down the inner glass wall rather than squirting it directly onto the powder. Let the peptide dissolve, swirl gently, and never shake — agitation causes foaming and can damage the peptide.

Concentration is simply the mass of peptide divided by the volume of water added. Adding more water gives a lower concentration:

VialBacteriostatic water addedResulting concentration
10 mg1 ml10 mg/ml
10 mg2 ml5 mg/ml
15 mg1.5 ml10 mg/ml
15 mg3 ml5 mg/ml
20 mg2 ml10 mg/ml

Once reconstituted, store the vial refrigerated at 2–8 °C and use it within a few weeks (see Storage). Maintain sterility throughout and label the vial with the concentration and preparation date.

Comparison with Related Compounds

Survodutide sits within the incretin "agonism ladder" as one of the two leading GLP-1/glucagon dual agonists — alongside Mazdutide — distinguished by its strong MASH and liver-fibrosis data. The table below places it against the other most-studied metabolic research peptides by receptor targets and headline trial effect. For the mechanistic detail behind these classes, see GLP-1 vs GIP vs glucagon.

CompoundReceptor targetsClassHeadline trial effectSchedule
SurvodutideGLP-1 + GlucagonDual~19% wt (Ph2); strong MASH/fibrosis dataOnce weekly
MazdutideGLP-1 + GlucagonDual~14% (Ph3, 48 wk)Once weekly
RetatrutideGIP + GLP-1 + GlucagonTriple~24.2% (Ph2, 48 wk)Once weekly
SemaglutideGLP-1Mono~15% (Ph3, 68 wk)Once weekly
TirzepatideGIP + GLP-1Dual~22.5% (Ph3, 72 wk)Once weekly

Survodutide and Mazdutide are the two GLP-1/glucagon dual agonists in this comparison; both harness the glucagon "energy-out" arm, but Survodutide's defining distinction is the strength of its MASH and liver-fibrosis data, which earned it FDA Breakthrough Therapy designation. The triple agonist Retatrutide adds a third (GIP) target and posts the largest weight-loss figures, while Tirzepatide and Semaglutide anchor the dual GIP/GLP-1 and GLP-1-only ends of the ladder. To compare live pricing and strengths, see the buy Survodutide UK and buy Retatrutide UK pages.

References

The findings above are drawn from the following peer-reviewed publications and trial registrations. Links open on the publisher or registry site.

  1. le Roux CW, et al. Glucagon and GLP-1 receptor dual agonist survodutide for obesity: a randomised, double-blind, placebo-controlled, dose-finding phase 2 trial. Lancet Diabetes Endocrinol. 2024.
  2. Sanyal AJ, et al. A Phase 2 Randomized Trial of Survodutide in MASH and Fibrosis. N Engl J Med. 2024.
  3. Boehringer Ingelheim. Survodutide obesity Phase 3 (SYNCHRONIZE). ClinicalTrials.gov.
  4. Boehringer Ingelheim. Survodutide MASH trial. ClinicalTrials.gov.

Frequently Asked Questions

What is Survodutide used for in research?+
Survodutide (BI 456906) is studied as a dual GLP-1/glucagon receptor agonist, primarily in metabolic research contexts — obesity and metabolic dysfunction-associated steatohepatitis (MASH) models. It is supplied strictly for in vitro laboratory research and is not for human use.
How does Survodutide differ from Mazdutide, Retatrutide and Semaglutide?+
Semaglutide targets one receptor (GLP-1); Survodutide and Mazdutide are dual GLP-1/glucagon agonists; Retatrutide is a triple GIP/GLP-1/glucagon agonist. Among the duals, Survodutide is distinguished by its strong MASH and liver-fibrosis data.
What did the Survodutide MASH trial show?+
In a Phase 2 trial in biopsy-confirmed MASH with F1–F3 fibrosis, Survodutide improved MASH without worsening fibrosis in 47% (2.4 mg), 62% (4.8 mg) and 43% (6.0 mg) of participants versus 14% on placebo — data that led to FDA Breakthrough Therapy designation for MASH in 2024.
What is Survodutide's half-life and schedule?+
Survodutide is engineered for a long duration of action supporting a once-weekly research schedule, achieved through fatty-acid conjugation and albumin binding that slow clearance. Steady state is reached after several half-lives.
Is Survodutide approved or legal to buy?+
Survodutide is an investigational compound not approved by the MHRA, FDA or any regulator. It is legitimately supplied and purchased as a research reagent for in vitro use — not for human consumption.
Where can I buy research-grade Survodutide in the UK?+
RS Bio Labs supplies Survodutide in three strengths at ≥99% purity and free UK shipping. See the buy Survodutide UK page for live pricing.

Glossary

Dual agonist
A single molecule that activates two different receptors at once. Survodutide activates the GLP-1 and glucagon receptors.
GLP-1 (glucagon-like peptide-1)
An incretin hormone that promotes satiety, slows gastric emptying and stimulates glucose-dependent insulin release.
Glucagon receptor (GCGR)
Receptor whose activation raises hepatic glucose output and lipolysis, increases resting energy expenditure and drives mobilisation of liver fat.
MASH
Metabolic dysfunction-associated steatohepatitis — an advanced form of fatty-liver disease with inflammation and liver-cell injury, the primary condition in which Survodutide's histological benefit was demonstrated.
MASLD
Metabolic dysfunction-associated steatotic liver disease — the broader fatty-liver spectrum of which MASH is the more severe, inflammatory stage.
Fibrosis
Scarring of liver tissue that accumulates with progressive liver disease; the MASH trial measured improvement in MASH without worsening of fibrosis stages F1–F3.
Incretin
A gut hormone released after eating that augments insulin secretion; GLP-1 is a principal incretin.
Breakthrough Therapy designation
An FDA status that expedites development of a compound showing substantial improvement over available options; granted to Survodutide for MASH in 2024.
Lyophilised
Freeze-dried. Removing water greatly increases a peptide's shelf stability.
Bacteriostatic water
Sterile water containing 0.9% benzyl alcohol, used as the standard diluent for reconstituting multi-use research vials.
Half-life
The time for plasma concentration to fall by half; Survodutide's is long enough to support once-weekly dosing.
Resting energy expenditure
The energy the body uses at rest; increasing it is the distinguishing effect of the glucagon arm.
Research Context: Survodutide is an investigational compound in active Phase 3 clinical development by Boehringer Ingelheim and Zealand Pharma. It has not been approved by the MHRA, FDA or any other regulatory authority. All efficacy and safety statements above derive exclusively from published preclinical research and clinical-trial readouts. RS Bio Labs supplies Survodutide as a research-grade laboratory compound for in vitro scientific use only. It is not for human consumption, self-administration, veterinary use, or therapeutic application. This profile is for educational and scientific reference only and does not constitute medical advice.