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A glucagon-based dual agonist in the next wave of metabolic peptide research.
Also known as: BI 456906 · EX-A7878 · glucagon/GLP-1 dual agonist
Part of the Metabolic & GLP-1 peptides cluster
Overview
Survodutide (BI 456906) is an investigational 29-amino-acid glucagon-based peptide (C192H289N47O61, ≈4,232 Da) that activates both the glucagon and GLP-1 receptors. Developed by Boehringer Ingelheim and Zealand Pharma, it carries an Aib at position 2 and a C18 fatty diacid for once-weekly dosing. Phase 2 produced up to −14.9% body weight at 46 weeks and a large improvement in MASH; phase 3 trials are ongoing.
Source & context
Biological / chemical source: Synthetic acylated peptide (Boehringer Ingelheim)
Primary research or clinical context: Investigational — phase 3 trials in obesity (SYNCHRONIZE) and in MASH; not approved as of September 2026
What survodutide is
Survodutide is a once-weekly peptide from Boehringer Ingelheim and Zealand Pharma, known in the literature as BI 456906. Unlike tirzepatide and retatrutide, which start from GIP, survodutide starts from glucagon: it is a 29-residue glucagon analogue re-engineered so that it also activates the GLP-1 receptor. Its molecular formula is C192H289N47O61 and its average molecular weight is about 4,232 Da. As of September 2026 it is in phase 3 trials for obesity and for metabolic dysfunction-associated steatohepatitis (MASH) and is not approved anywhere.
Glucagon receptor agonism: why and how it is balanced
Glucagon is the hormone that raises blood glucose, so building a weight-loss drug on it sounds paradoxical. The rationale is that glucagon also increases energy expenditure, promotes fat oxidation in the liver and reduces food intake — effects that GLP-1 agonists do not provide. The risk is hyperglycaemia, and the answer is balance: pairing glucagon receptor activity with enough GLP-1 receptor activity that insulin secretion and appetite suppression more than offset the glucose-raising effect. Survodutide's discovery paper (Zimmermann et al., Mol Metab 2022) describes tuning the two potencies so that in animal models weight fell substantially while glucose control improved. The same logic, with GIP added, underlies retatrutide.
Structure
Survodutide keeps glucagon's 29-residue length, replaces serine 2 with Aib to block DPP-4, introduces several GLP-1-like substitutions along the chain to gain GLP-1 receptor activity, attaches a C18 fatty diacid through a γ-glutamate and a short spacer to a lysine side chain for albumin binding, and ends in a C-terminal amide. The full one-letter sequence has been deposited (PubChem CID 171378821; IUPHAR ligand 13383) but is not reproduced residue-by-residue here because published sources differ in how the spacer is described. The design places it in the same lipidated, once-weekly class as semaglutide, tirzepatide and retatrutide.
Phase 2 results in obesity
The phase 2 dose-finding trial (le Roux et al., Lancet Diabetes & Endocrinology 2024; 387 adults without diabetes, 46 weeks) tested 0.6, 2.4, 3.6 and 4.8 mg once weekly against placebo. Mean weight change by planned treatment was −6.2%, −12.5%, −13.2% and −14.9% respectively, versus −2.8% with placebo. Adverse events occurred in 91% of survodutide recipients versus 75% on placebo, primarily gastrointestinal (75% vs 42%), and only 60% of participants completed the 46-week period — a high discontinuation rate that the phase 3 programme addresses with slower dose escalation.
| Arm | Weight change |
|---|---|
| Placebo | −2.8% |
| 0.6 mg | −6.2% |
| 2.4 mg | −12.5% |
| 3.6 mg | −13.2% |
| 4.8 mg | −14.9% |
MASH: where the glucagon component shows
Glucagon receptor activation drives hepatic fat oxidation, so survodutide's most distinctive data are in liver disease. In a phase 2 trial in biopsy-confirmed MASH with fibrosis (Sanyal et al., NEJM 2024), 48 weeks of survodutide produced histological improvement in MASH without worsening of fibrosis in up to 83% of participants at the higher doses, versus about 18% with placebo. That result led to phase 3 trials in MASH running in parallel with the obesity programme, and it is the main reason survodutide is watched despite its weight-loss numbers trailing tirzepatide and retatrutide.
Survodutide vs mazdutide vs retatrutide
Survodutide and mazdutide are both glucagon/GLP-1 dual agonists, but from different scaffolds — glucagon and oxyntomodulin respectively — and mazdutide is approved in China while survodutide is not yet approved anywhere. Retatrutide adds a third receptor (GIP) on a GIP-derived scaffold and has produced larger weight loss in phase 2 (−24.2% at 48 weeks versus survodutide's −14.9% at 46 weeks, in different populations). Survodutide's differentiator is its MASH evidence. None of the three has head-to-head data against the others.
Structure & chemistry
Molecular identity & reference confidence
Source-supported reference
Registry records link different PubChem CIDs. Their molecular forms have not been reconciled; generated cross-source identifiers are not combined. Any retained curated chemistry describes its explicitly selected PubChem form.
- Molecular form
- 29-residue human-glucagon-derived scaffold (glucagon itself starts H-S-Q-G-T-F-T-S-D-Y-S-K-Y-L-D-S-R-R-A-Q-D-F-V-Q-W-L-M-N-T)
- Species
- Not established by this molecular identity audit
- Termini (N / C)
- Not specified / Amide
Average reference mass
Reference policy updated: 2026-10-05
- IUPHAR/BPS source snapshot · 2026-10-01
- PubChem molecular record · 2026-10-01
- Molecular formula
- C192H289N47O61
- Average reference mass
- ≈ 4,232
- Plasma half-life
- Supports once-weekly dosing (published population estimates are on the order of several days)
- Receptors
- Glucagon receptor (GCGR) and GLP-1 receptor — balanced so glucagon's energy-expenditure and hepatic effects are captured without hyperglycaemia
- Backbone
- 29-residue human-glucagon-derived scaffold (glucagon itself starts H-S-Q-G-T-F-T-S-D-Y-S-K-Y-L-D-S-R-R-A-Q-D-F-V-Q-W-L-M-N-T)
- Lipidation
- Octadecanedioic acid (C18 fatty diacid) → γ-glutamate → short spacer → lysine side chain
- C-terminus
- Amide
- Status
- Investigational (phase 3: SYNCHRONIZE obesity programme; MASH programme). Not approved as of September 2026
| Position | Native | Analog | Purpose |
|---|---|---|---|
| Position 2 | Ser (glucagon) | Aib | DPP-4 resistance |
| Mid-chain substitutions | Glucagon residues | GLP-1-like residues | Adds GLP-1 receptor activity to a glucagon scaffold |
| Lysine side chain | — | C18 diacid-γGlu-spacer | Albumin binding for once-weekly pharmacokinetics |
| C-terminus | Thr29 free acid | Amide | Stability |
- PubChem CID: 171378821
- CAS RN: 2805997-46-8
Chemistry values: curated profile · fetched 2026-10-01.
Clinical development snapshot
ClinicalTrials.gov lists 28 registered studies with “Survodutide” as an intervention (snapshot 2026-10-01). A registry footprint is not evidence of efficacy or approval.
| NCT | Title | Phase | Status | Updated |
|---|---|---|---|---|
| NCT06632444 | LIVERAGE™: A Study to Test Whether Survodutide Helps People With a Liver Disease Called NASH/MASH Who Have Mod | Phase 3 | recruiting | 2026-10-01 |
| NCT06632457 | LIVERAGE™ - Cirrhosis: A Study to Test Whether Survodutide Helps People With a Liver Disease Called NASH/MASH | Phase 3 | recruiting | 2026-10-01 |
| NCT07754461 | A Study to Test Whether Survodutide Helps People With Type 2 Diabetes Control Their Blood Sugar | Phase 3 | recruiting | 2026-09-30 |
| NCT06077864 | A Study to Test the Effect of Survodutide (BI 456906) on Cardiovascular Safety in People With Overweight or Ob | Phase 3 | completed | 2026-09-30 |
| NCT07850050 | SYNCHRONIZE®-HERA: A Study to Test Whether Survodutide Helps Women Who Are Living With Overweight or Obesity a | Phase 3 | not yet recruiting | 2026-09-30 |
| NCT07850063 | ELEVATE-LIVER: A Study to Test Whether Survodutide Helps Improve Heart Structure and Function in People With O | Phase 3 | not yet recruiting | 2026-09-30 |
The incretin & metabolic co-agonist class at a glance
| Peptide | Receptors | Length | Mass (Da) | Half-life | Status |
|---|---|---|---|---|---|
| GLP-1 | GLP-1R | 30 aa | ≈ 3,297.6 | ≈ 1–2 min (DPP-4 cleavage + renal clearance) | Endogenous hormone — not a product |
| Liraglutide | GLP-1R | 31 aa | ≈ 3,751.2 | ≈ 13 h (once-daily dosing) | Approved: Victoza (2010, T2D), Saxenda (2014, weight) |
| Semaglutide | GLP-1R | 31 aa | ≈ 4,113.6 | ≈ 7 days (≈ 145–165 h in clinical PK studies) | Approved: Ozempic (2017, T2D), Rybelsus (2019, oral T2D), Wegovy (2021, weight) |
| Tirzepatide | GIPR + GLP-1R | 39 aa | ≈ 4,813.5 | ≈ 5 days (≈ 117 h) | Approved: Mounjaro (2022, T2D), Zepbound (2023, weight; 2024, obstructive sleep apnoea) |
| Retatrutide | GIPR + GLP-1R + GCGR | 39 aa | ≈ 4,731 | ≈ 6 days | Investigational (phase 3) |
| Cagrilintide | Amylin / calcitonin | 37 aa | ≈ 4,409 | ≈ 7–8 days (159–195 h across doses in the phase 1b study) | Investigational (phase 3, as CagriSema with semaglutide) |
| Survodutide (this page) | GCGR + GLP-1R | 29 aa | ≈ 4,232 | Supports once-weekly dosing (published population estimates are on the order of several days) | Investigational (phase 3: SYNCHRONIZE obesity programme; MASH programme) |
| Mazdutide | GCGR + GLP-1R | 34 aa | ≈ 4,476 | Supports once-weekly dosing (published estimates are on the order of several days) | Approved in China (NMPA): chronic weight management (27 June 2025) and type 2 diabetes (2025) |
| Amycretin | GLP-1R + amylin | — | — | Supports once-weekly subcutaneous dosing | Investigational (phase 2 results published 2025; later-phase trials under way) |
Verified from PubChem, IUPHAR and the primary discovery papers cited on each profile. Half-lives are approximate population means from published pharmacokinetics.
Survodutide — reconstitution calculator
Enter how much peptide is in the vial and how much diluent (e.g. bacteriostatic water) is added. The tool returns the resulting solution concentration — and, for any amount you type, the volume it corresponds to. This is educational arithmetic, not a dosing recommendation.
Reference form: 29-residue human-glucagon-derived scaffold (glucagon itself starts H-S-Q-G-T-F-T-S-D-Y-S-K-Y-L-D-S-R-R-A-Q-D-F-V-Q-W-L-M-N-T)Average reference mass: 4,232 Da
Enter an amount to see the volume it corresponds to.
Educational concentration mathematics only. This tool does not recommend a dose, amount, or protocol, and nothing here is medical advice. Many peptides are not authorized by Health Canada for human use — see our reconstitution and bacteriostatic-water guides for context.
Change log
Dated observations from the data pipeline (registry flags, trial footprints, identifiers) and editorial reviews of this profile.
- Trials2 registered studies added on ClinicalTrials.gov (now 28).
- EditorialProfile content reviewed and updated by the editorial team.
FAQ about Survodutide
What is Survodutide?+
Survodutide (BI 456906) is an investigational 29-amino-acid glucagon-based peptide (C192H289N47O61, ≈4,232 Da) that activates both the glucagon and GLP-1 receptors. Developed by Boehringer Ingelheim and Zealand Pharma, it carries an Aib at position 2 and a C18 fatty diacid for once-weekly dosing. Phase 2 produced up to −14.9% body weight at 46 weeks and a large improvement in MASH; phase 3 trials are ongoing.
What Canadian product status is recorded for Survodutide?+
Canadian product status for Survodutide has not been verified in this profile. No verified record here does not mean no authorization exists. Status depends on the product, formulation and use; consult Health Canada's product records.
What is the typical length of Survodutide?+
Survodutide is commonly described as approximately 29 amino acids (Dual GLP-1 / glucagon receptor agonist (investigational)).
What is survodutide?+
An investigational once-weekly peptide (BI 456906) from Boehringer Ingelheim and Zealand Pharma that activates the glucagon and GLP-1 receptors. It is a 29-residue glucagon analogue with a C18 fatty diacid; formula C192H289N47O61, mass about 4,232 Da.
Is survodutide approved?+
No. As of September 2026 it is in phase 3 trials for obesity (SYNCHRONIZE) and MASH and has not been approved in any country.
How much weight loss did survodutide produce?+
In phase 2, up to −14.9% at 46 weeks on 4.8 mg weekly versus −2.8% with placebo (planned-treatment analysis). Phase 3 results are pending.
How does survodutide differ from retatrutide?+
Survodutide activates two receptors (glucagon + GLP-1) from a glucagon-based sequence; retatrutide activates three (GIP + GLP-1 + glucagon) from a GIP-based sequence and has shown larger weight loss in phase 2. Survodutide has stronger published MASH data.
Further reading
- FoundationsGLP-1 vs GIP vs Glucagon: Incretin Receptor Classes ExplainedAn educational overview of the incretin and metabolic receptor classes—GLP-1, GIP, and glucagon—and how single, dual, and triple receptor agonism differ mechanistically.
- Metabolic peptidesGLP-1 Peptides Explained: GLP-1, Semaglutide, Tirzepatide, RetatrutideFrom endogenous GLP-1 to dual and triple agonists—an educational map of incretin peptide science and metabolic drug design.
- PharmacologyGLP-1 and Incretin Peptide Half-Lives Compared: From 2 Minutes to 8 DaysA sourced table of the plasma half-lives of native GLP-1, exenatide, liraglutide, dulaglutide, semaglutide, tirzepatide, retatrutide, cagrilintide and the newer co-agonists — and the three engineering strategies (DPP-4 resistance, albumin binding, Fc fusion) that stretch minutes into a week.
Related peptides
References & further reading
- 1.Sanyal et al. (2024). A Phase 2 Randomized Trial of Survodutide in MASH and Fibrosis. N Engl J Med
- 2.le Roux 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
- 3.le Roux et al. (2026). Survodutide Once Weekly for the Treatment of Adults with Obesity. N Engl J Med
- 4.Kosiborod et al. (2024). Survodutide for the Treatment of Obesity: Rationale and Design of the SYNCHRONIZE Cardiovascular Outcomes Trial. JACC Heart Fail
- 5.Blüher et al. (2024). Dose-response effects on HbA(1c) and bodyweight reduction of survodutide, a dual glucagon/GLP-1 receptor agonist, compared with placebo and open-label semaglutide in people with type 2 diabetes: a randomised clinical trial. Diabetologia
- 6.le Roux et al. (2026). Survodutide for treatment of obesity: Baseline characteristics of participants in a randomized, double-blind, placebo-controlled, phase 3 trial (SYNCHRONIZE™-1). Diabetes Obes Metab
- 7.Thomas et al. (2024). The dual GCGR/GLP-1R agonist survodutide: Biomarkers and pharmacological profiling for clinical candidate selection. Diabetes Obes Metab
- 8.Lawitz et al. (2024). Efficacy, tolerability and pharmacokinetics of survodutide, a glucagon/glucagon-like peptide-1 receptor dual agonist, in cirrhosis. J Hepatol
- 9.PubChem — compound summary for Survodutide (CID 168429725)
- 10.Wikipedia — Survodutide