Survodutide

BI 456906, glucagon/GLP-1 receptor dual agonist

Metabolic & weight

Awaiting medical reviewEN ES DE FR PT ZH+ Follow for updates

Note on this profile. Survodutide is an investigational medicine in late-stage clinical trials (Boehringer Ingelheim, licensed from Zealand Pharma). It is not approved anywhere and is not legitimately available outside a trial. Anything sold under this name is unverified grey-market material. This page explains the published science only.

Summary

Class: Synthetic 29-amino-acid glucagon analogue with a C18 fatty-acid side chain; dual agonist at the glucagon receptor and the GLP-1 receptor
Mechanism: Reduces appetite and improves glucose handling through GLP-1 receptor activation while raising energy expenditure and liver fat breakdown through glucagon receptor activation
Routes studied: Subcutaneous once-weekly injection (all human trials)
Dose range reported: Phase 2: 0.6, 2.4, 3.6 and 4.8 mg once weekly, reached by slow upward titration over up to 20 weeks. Phase 3 uses 3.6 and 6.0 mg weekly. No approved dose; no community dosing convention exists and none is reported here
Half-life: Long enough for once-weekly dosing; reported in the range of several days †
Storage: Trial product supplied as a solution in prefilled devices, refrigerated. No handling guidance exists for non-trial material
Regulatory status: Investigational (Phase 3) worldwide; FDA Breakthrough Therapy designation for MASH with fibrosis (2024)

Doses are as reported in studies or by the community — never recommendations.

1What it is

Survodutide is a modified version of glucagon, the hormone the pancreas releases when blood sugar falls. Chemists changed enough of the sequence that it also activates the GLP-1 receptor (the target of semaglutide), and attached a fatty acid so it binds albumin and lasts a week. Zealand Pharma designed it; Boehringer Ingelheim has run the clinical programme since 2011.

The idea behind dual agonism is that GLP-1 action lowers food intake while glucagon action increases energy burn and pulls fat out of the liver, so the two together might outperform GLP-1 alone, particularly for fatty liver disease. Survodutide is one of several "multi-agonists" (alongside tirzepatide, retatrutide and mazdutide) racing through late-stage trials.

2How it's thought to work

GLP-1 receptor. glucose-dependent insulin release, slowed gastric emptying, reduced appetite via the hypothalamus and brainstem — the familiar GLP-1 package.

Glucagon receptor. increased hepatic fat oxidation, modestly higher energy expenditure and reduced liver fat. Glucagon alone raises blood sugar, but in combination the GLP-1 component appears to offset this.

Balance of the two. survodutide is tuned to be more potent at the glucagon receptor than most rivals, which is thought to explain the strong liver signal and also contributes to the gastrointestinal tolerability challenge.

A GLP-1 and glucagon dual agonist in late-stage trials for obesity and for liver disease, where the glucagon arm is thought to do most of the work on hepatic fat.Schematic — not to scale

3What the research shows

Weight loss in obesity

A 46-week Phase 2 trial in 387 adults with overweight or obesity without diabetes reported mean weight loss of up to 14.9% at the 4.8 mg dose in the planned-treatment analysis, and up to 18.7% in those who stayed on treatment, versus about 2.8% with placebo (le Roux 2024, Lancet Diabetes Endocrinol). Weight was still falling at week 46. Discontinuation for adverse events was high (around a quarter of participants on the top doses), mostly during fast titration — the Phase 3 design slowed the ramp-up in response. [1]

Metabolic dysfunction-associated steatohepatitis (MASH)

A 48-week Phase 2 trial in 293 adults with biopsy-confirmed MASH and fibrosis stages F1–F3 reported histological improvement in MASH without worsening of fibrosis in up to 83% of participants on 6.0 mg versus 18% on placebo, with meaningful reductions in liver fat (Sanyal 2024, NEJM). Improvement in fibrosis by at least one stage was seen in roughly half of treated participants in exploratory analyses. This result drove the FDA Breakthrough Therapy designation. [2]

Type 2 diabetes glucose control

A 16-week Phase 2 trial in people with type 2 diabetes reported HbA1c reductions of around 1.5–1.7 percentage points at higher doses alongside weight loss, compared with semaglutide 1 mg as an active comparator (Blüher 2024, Diabetes Obes Metab). [3]

Graded A/B

Phase 1 pharmacology

Single and multiple ascending dose studies in healthy and overweight volunteers established the weekly pharmacokinetic profile and dose-dependent weight loss over 16 weeks (Jungnik 2023, Diabetes Obes Metab). [4]

Preclinical pharmacology

In diet-induced obese mice, BI 456906 produced greater weight loss than semaglutide at matched GLP-1 receptor exposure, with reduced liver triglycerides and increased energy expenditure attributable to the glucagon component (Zimmermann 2022, Mol Metab). Rodent glucagon biology differs from human, so these figures are directional only. [5]

Not gradedpending

Phase 3 (SYNCHRONIZE-1, -2, -CVOT, and MASH LIVERAGE)

Large trials in obesity with and without diabetes, a cardiovascular outcomes trial and Phase 3 MASH trials began in 2023–2024. Topline results were expected during 2026 †.

4Reported side effects and interactions

Literature-reported

Gastrointestinal effects dominate — nausea (over half of participants at higher doses in Phase 2), vomiting, diarrhoea, constipation — mostly during titration. Increased heart rate of several beats per minute, consistent with glucagon and GLP-1 class effects. Gallbladder events and transient liver-enzyme rises have been reported in the class and are being tracked.

Community-reported

essentially none in the published or forum record because the compound is not in circulation outside trials; treat any claims as unverified.

Theoretical. glucagon-receptor activation could raise blood glucose in the absence of adequate GLP-1 effect; loss of lean mass alongside fat as with other incretin-based agents; class-level thyroid C-cell concern from rodent GLP-1 data; effects in pregnancy unknown.

Interactions. additive hypoglycaemia risk with insulin or sulfonylureas; slowed gastric emptying may alter absorption of oral medicines. No formal interaction studies are published.

Markers researchers commonly monitor

Marker	Why it's watched
Body weight and waist circumference	primary efficacy readouts in every trial.
HbA1c and fasting glucose	glucagon-receptor activation could in principle push glucose up; trials show net lowering, but this is the key balance to watch.
Liver enzymes (ALT, AST), liver fat by imaging (MRI-PDFF) and non-invasive fibrosis scores (FIB-4, ELF)	the MASH endpoints.
Resting heart rate	rises of a few beats per minute are a class effect.
Lipid panel	triglyceride and LDL changes reported in trials.
Amylase, lipase and gallbladder symptoms	pancreatitis and gallstone signals are tracked across the incretin class.
Lean mass (DEXA where available)	muscle loss accompanies rapid weight loss.

Free for everyone. Safety information is never behind a paywall.

5Reconstitution and handling

Not applicable. Survodutide exists only as trial-supplied solution. No product has ever been made for legitimate use, so any vial sold as "survodutide" has no reference standard and cannot be assumed to contain the molecule. The calculator does not carry a preset for this compound.

Open in calculator, pre-loaded →

6Commonly studied alongside

Studied as monotherapy against placebo and against semaglutide. Discussed in the literature in comparison with tirzepatide, retatrutide, mazdutide, pemvidutide and efinopegdutide (other glucagon-containing multi-agonists), never in combination with them.

Informational cross-links. Not stack recommendations.

7Regulatory status by region

Region	Status (checked —)
United States	Not approved; investigational (Phase 3). Breakthrough Therapy designation for MASH (2024). Not eligible for compounding
European Union	Not authorised; investigational
United Kingdom	Not licensed; investigational
Australia	Not approved; investigational
South Africa	Not registered
Sport	GLP-1 receptor agonists are not on the WADA Prohibited List as of 2026; glucagon itself is not prohibited †

8Open questions

Does the glucagon component add meaningful liver and energy-expenditure benefit over GLP-1 alone once Phase 3 head-to-head data arrive?
Can slower titration in Phase 3 bring discontinuation rates down to tirzepatide-like levels?
Durability of MASH histological improvement and whether fibrosis regression is confirmed.
Long-term cardiovascular safety given the heart-rate effect (SYNCHRONIZE-CVOT).

9References

1le Roux CW et al. (2024). Glucagon and GLP-1 receptor dual agonist survodutide for obesity: a randomised, double-blind, placebo-controlled, dose-finding phase 2 trial. Lancet Diabetes Endocrinol. DOI
2Sanyal AJ et al. (2024). A phase 2 randomized trial of survodutide in MASH and fibrosis. N Engl J Med. PubMed · DOI
3Blüher M et al. (2024). Dose-response effects on HbA1c and bodyweight of survodutide, a dual glucagon/GLP-1 receptor agonist, in people with type 2 diabetes: a phase 2 randomised trial. Diabetes Obes Metab. PubMed
4Jungnik A et al. (2023). Phase I studies of the safety, tolerability, pharmacokinetics and pharmacodynamics of the dual glucagon receptor/glucagon-like peptide-1 receptor agonist BI 456906. Diabetes Obes Metab. PubMed · DOI
5Zimmermann T et al. (2022). BI 456906: discovery and preclinical pharmacology of a novel GCGR/GLP-1R dual agonist with robust anti-obesity efficacy. Mol Metab. PubMed · DOI

References are being resolved to PubMed/DOI identifiers; links search PubMed for the citation until then.

† Being confirmed by our reviewers against current sources.

10Community

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Self-reported side effects Phase 2

Not enough data yet. 0 of the 50 members needed have logged this compound for 4+ weeks. We don't show anything below 50, so no one can be identified.

11Page history

25 Oct 2026Profile published — awaiting medical review

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