Survodutide
BI 456906 · GLP-1/glucagon dual agonist
−14.9% body weight at 46 weeks, 4.8 mg (Phase 2, planned-treatment analysis)
Overview
Survodutide is an investigational once-weekly peptide that activates two receptors at once: the glucagon-like peptide-1 (GLP-1) receptor, shared with the approved incretin drugs, and the glucagon receptor. The GLP-1 arm drives appetite suppression and glucose-dependent insulin release, while the added glucagon-receptor activity is intended to raise energy expenditure and mobilize hepatic fat — the same rationale behind the glucagon component of the triple agonist retatrutide, but without GIP activity.
In a 386-participant Phase 2 dose-finding trial (adults with obesity, without diabetes; 46 weeks), the 4.8 mg dose produced a mean body-weight reduction of about 14.9% in the planned-treatment analysis versus roughly 2.8% on placebo, rising to about 18.7% among participants who completed treatment per protocol. Lower doses fell on a clear dose–response curve (about −6.2%, −12.5%, and −13.2% at 0.6, 2.4, and 3.6 mg). A majority of the 4.8 mg group lost at least 15% of body weight, and a separate Phase 2 program in MASH reported substantial liver-fat reductions.
Tolerability in the obesity trial mirrored the GLP-1 class — gastrointestinal effects predominated — but a rapid two-weekly dose-escalation schedule appears to have contributed to a relatively high discontinuation rate, which the slower Phase 3 titration is designed to improve. All figures here summarize the published Phase 2 reporting and are provided strictly as a research reference.
Key parameters
- Dose range
- 0.6–4.8 mg weekly (trial range)
- Frequency
- Once weekly
- Half-life
- ~100 hours (supports once-weekly dosing)
- Route
- Subcutaneous
- Vial sizes
- 5 mg · 10 mg
- Regulatory status
- Investigational. A dual GLP-1 / glucagon receptor agonist from Boehringer Ingelheim, in Phase 3 development (SYNCHRONIZE program) for obesity and separately studied for MASH/NASH as of 2026; not approved by any regulator. Research-vial material is for laboratory use only.
Mechanism of action
GLP-1 receptor agonism
Engages GLP-1 receptors in appetite-regulating brain regions and the pancreas, reducing energy intake and stimulating glucose-dependent insulin secretion with low intrinsic hypoglycemia risk.
Glucagon receptor agonism
Adds glucagon-receptor signaling that is thought to increase resting energy expenditure and promote hepatic lipolysis, the basis for the marked liver-fat reductions seen in its MASH program.
Hepatic fat mobilization
The combination shifts the liver toward fat oxidation and reduced steatosis, distinguishing dual GLP-1/glucagon agonists from GLP-1-only agents in metabolic-liver-disease research.
Dosing protocol & phases
| Phase | Weeks | Dose | Notes |
|---|---|---|---|
| Initiation | Weeks 1–2 | 0.6 mg once weekly | Low starting dose for tolerability. |
| Escalation | Through ~week 20 | Step up every ~2 weeks toward target | Phase 2 used a rapid two-weekly escalation; this aggressive pace likely raised the discontinuation rate. |
| Maintenance | Weeks ~20–46 (trial) | Up to 4.8 mg once weekly | Highest dose studied; doses of 2.4, 3.6, and 4.8 mg all produced double-digit weight loss. |
Reconstitution guide
For educational and research reference only. Not intended for human consumption, not medical advice. Compounds discussed are sold and used for laboratory research purposes only.
10 mg vial + 2 mL bacteriostatic water
Concentration5,000 mcg/mL · 5 mg/mL
| Target dose | Draw volume | U-100 units |
|---|---|---|
| 600 mcg | 0.12 mL | 12 |
| 2,400 mcg | 0.48 mL | 48 |
| 3,600 mcg | 0.72 mL | 72 |
| 4,800 mcg | 0.96 mL | 96 |
Standard mix; keeps the early titration draws small and the 4.8 mg dose inside a 100-unit syringe.
10 mg vial + 1 mL bacteriostatic water
Concentration10,000 mcg/mL · 10 mg/mL
| Target dose | Draw volume | U-100 units |
|---|---|---|
| 2,400 mcg | 0.24 mL | 24 |
| 3,600 mcg | 0.36 mL | 36 |
| 4,800 mcg | 0.48 mL | 48 |
Higher-strength mix that halves the draw volume for the maintenance range.
Reconstitution calculator
Pre-filled with Survodutide's vial sizes. Adjust the water volume and target dose to see the exact draw, with warnings for doses that are hard to measure or won't fit a syringe.
At 2,500 micrograms per millilitre, a 600 microgram dose is 0.24 millilitres, or 24 units on a U-100 syringe, giving 8 doses per vial.
Supplies needed
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Recommended supply
Survodutide — research vial
From our verified partner Dynotides, with a third-party certificate of analysis per batch.
Injection supplies
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Bacteriostatic water
Diluent for reconstituting lyophilized vials.
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Insulin syringes (U-100)
0.3–0.5 mL, 29–31 G for accurate small draws.
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Alcohol prep pads
Sterile swabs for the vial stopper and site.
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Sharps container
Safe disposal of used needles.
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Storage fridge
Keeps reconstituted vials at 2–8 °C.
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Insulated travel case
Cooled, TSA-friendly case for travel.
Missed-dose guidance
No approved-label guidance exists because survodutide is investigational. As a long-acting once-weekly agent, the practical convention used for comparable incretins is to take a delayed dose if several days remain before the next scheduled one and otherwise to skip it and resume the weekly schedule, without doubling up.
Side effects & safety
| Category | Effect | Trial incidence |
|---|---|---|
| Gastrointestinal | NauseaMost common adverse effect; dose-dependent and concentrated during the rapid escalation phase. A single exact incidence is not consistently reported, but GI events overall affected roughly 75% of survodutide participants versus ~43% on placebo. | — |
| Gastrointestinal | Vomiting | — |
| Gastrointestinal | Diarrhea | — |
| General | Treatment discontinuation due to adverse eventsDriven largely by GI effects during the fast two-weekly titration; Phase 3 uses a slower schedule to improve tolerability. | 24.6% |
| Cardiovascular | Modest heart-rate increaseConsistent with glucagon-containing agonists. | — |
| Serious | Serious treatment-related events (rare)Two medication-related serious adverse events were reported in Phase 2, both in the 3.6 mg group. | — |
Clinical trials & evidence
Phase 2 obesity dose-finding (le Roux et al.)
Phase 246 weeks · 386 adults with obesity (BMI ≥27), without diabetes
−14.9% body weight at 4.8 mg (planned-treatment) vs −2.8% placebo; up to −18.7% per-protocol; 55% of the 4.8 mg arm lost ≥15%.
NCT04667377 ↗Phase 2 MASH/NASH trial
Phase 248 weeks · Adults with biopsy-confirmed MASH and fibrosis
Significantly more participants achieved MASH improvement without fibrosis worsening versus placebo; large liver-fat reductions.
NCT04771273 ↗SYNCHRONIZE-1 (Phase 3)
Phase 3Ongoing · Adults with obesity/overweight
Confirmatory obesity efficacy and safety study; results pending.
NCT06066515 ↗
Storage & handling
- Lyophilized
- Refrigerate the lyophilized powder at 2–8 °C, protected from light; brief room-temperature excursions in transit are generally tolerated for peptides of this class.
- Reconstituted
- Refrigerate at 2–8 °C and use within ~28 days; do not freeze.
Comparisons
| Vs. | Target | Half-life | Dosing | Efficacy | Status |
|---|---|---|---|---|---|
| Retatrutide | GLP-1 + glucagon vs GIP + GLP-1 + glucagon | ~100 h vs ~6 d | Weekly (both) | −14.9% (planned-treatment) vs −24.2% (different Phase 2 trials) | Both investigational |
| Semaglutide | GLP-1 + glucagon vs GLP-1 only | ~100 h vs ~7 d | Weekly (both) | Similar headline weight loss to semaglutide, with added liver-fat effect | Investigational vs approved |
Sources & references
- [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. ↗ source
- [2]Sanyal AJ et al. A Phase 2 Randomized Trial of Survodutide in MASH and Fibrosis. N Engl J Med 2024. ↗ source
- [3]ClinicalTrials.gov — Survodutide Phase 2 obesity dose-finding trial (NCT04667377). ↗ source
Frequently asked questions
How does survodutide differ from retatrutide?
Both add glucagon-receptor activity to a GLP-1 backbone, but retatrutide also activates the GIP receptor (a 'triple G' agonist) while survodutide is a dual GLP-1/glucagon agonist. In their separate Phase 2 trials retatrutide produced larger peak weight loss, though they have not been compared head-to-head.
Why was tolerability a concern in the Phase 2 trial?
The Phase 2 obesity study escalated the dose every two weeks, which is faster than comparable incretins. That pace concentrated gastrointestinal side effects and contributed to a discontinuation rate near 25%. The Phase 3 program uses a slower, more flexible titration to address this.
Is survodutide also being studied for liver disease?
Yes. A dedicated Phase 2 trial in metabolic dysfunction-associated steatohepatitis (MASH) reported significant improvements in liver histology and large reductions in liver fat, reflecting the glucagon component's effect on hepatic fat metabolism.
Related protocols
Retatrutide
LY3437943
−24.2% body weight at 48 weeks, 12 mg (Phase 2, NEJM 2023)
Tirzepatide
Mounjaro
−20.9% body weight at 72 weeks, 15 mg (SURMOUNT-1)
Semaglutide
Ozempic
−14.9% mean body weight at 68 weeks (STEP 1)
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For educational and research reference only. Not intended for human consumption, not medical advice. Compounds discussed are sold and used for laboratory research purposes only.