Survodutide
BI 456906 · BI-456906 · Survo
Weekly glucagon/GLP-1 dual agonist that raises energy expenditure as well as cutting appetite.
Typical dose
3.6 mg
once weekly
Range
0.3–6
mg
Half-life
6 days
see Dosing
Evidence
Human trials
Subcutaneous
What it is
Survodutide is a 29-amino-acid glucagon-based peptide, acylated with a C18 fatty diacid, that agonises both the glucagon receptor and the GLP-1 receptor. It is Boehringer Ingelheim's entry in the incretin race and sits in phase 3 for obesity and MASH.
The GLP-1 arm does what you would expect: appetite suppression, slowed gastric emptying, better glycaemic control. The glucagon arm is the differentiator — it increases energy expenditure and drives hepatic fat mobilisation, which is why survodutide's liver-fat and visceral-fat numbers stand out relative to its total weight loss.
Phase 2 produced 14.9% weight loss at 46 weeks at 4.8 mg on the primary planned-treatment analysis, against 2.8% on placebo; the actual-treatment sensitivity analysis reached about 19%. Phase 3 SYNCHRONIZE-1 reported up to 16.6% at 76 weeks. In MASH, phase 2 showed histological improvement without worsening of fibrosis in 43-62% of treated patients, against 14% on placebo.
The trade-off is tolerability. GI adverse events were common in phase 2, particularly on the faster titration arms, and the glucagon component nudges resting heart rate upward. Slow escalation is not optional with this one.
How it works
GLP-1 receptor activation in the hypothalamus and hindbrain reduces hunger and delays gastric emptying, the same mechanism as semaglutide. Glucagon receptor activation, mostly in the liver, increases hepatic fat oxidation and raises whole-body energy expenditure — glucagon burns substrate rather than storing it.
Running both together is a deliberate balancing act: glucagon alone would raise blood glucose, but the GLP-1 arm's insulinotropic effect offsets that, so the net result in trials was improved HbA1c alongside weight loss. Practically, you get appetite suppression plus a metabolic-rate contribution, which is why the visceral and liver fat reductions outpace what the scale weight alone would predict.
Dosing
3.6 mg and 6.0 mg are the two phase 3 maintenance targets; going straight to a maintenance dose without titrating is the single most common cause of people abandoning this compound.
Standard titration
| Step | Dose | Note |
|---|---|---|
| Weeks 1-4 | 0.3 mg | Starting dose |
| Weeks 5-8 | 0.6 mg | — |
| Weeks 9-12 | 1.2 mg | Hold here longer if nausea is still present |
| Weeks 13-16 | 2.4 mg | — |
| Weeks 17-20 | 3.6 mg | Lower phase 3 maintenance dose — many stop here |
| Weeks 21-24 | 4.8 mg | — |
| Week 25+ | 6 mg | Upper phase 3 maintenance dose; only if 4.8 mg is comfortable |
Reconstitution calculator
Pre-loaded with Survodutide’s vial size, water volume and typical dose. Change anything.
Typical: 3.6 mg · range 0.3–6
Draw to
72 u
0.72 mL · 3.6 mg
Concentration
5 mg/mL
50 mcg per unit
Doses per vial
1.4
Vial lasts
10 days
Draw to 72 units on the barrel.
Once mixed
2-8 C, use within about 4 weeks with bacteriostatic water. Do not freeze reconstituted solution.
1 mL of bacteriostatic water into a 5 mg vial gives 5 mg/mL, so 0.3 mg is 6 units and 3.6 mg is 72 units on a U-100 syringe. A 10 mg vial takes 2 mL for the same concentration. If you titrate past 5 mg per shot, mix the next vial thicker so the injection stays under 1 mL. Swirl gently, never shake.
Storage
Before mixing
2-8 C and out of light; the lyophilised powder is stable for well over a year and survives short unrefrigerated shipping.
After mixing
2-8 C, use within about 4 weeks with bacteriostatic water. Do not freeze reconstituted solution.
Reported benefits
- ▪14.9% weight loss at 46 weeks at 4.8 mg in phase 2 (primary analysis; ~19% on-treatment), ~16.6% at 76 weeks in phase 3
- ▪Glucagon arm adds energy expenditure rather than relying on appetite suppression alone
- ▪Large reductions in liver fat (up to ~63%) and visceral fat (up to ~34%)
- ▪Histological improvement in MASH in a phase 2 trial
- ▪HbA1c and blood pressure improvements in metabolic-syndrome populations
- ▪Once-weekly injection with pharmacokinetics unaffected by cirrhosis
Side effects
- ▪Nausea, vomiting and diarrhoea — frequent, and worse on fast titration than with pure GLP-1 agonists
- ▪Constipation and reflux
- ▪Resting heart rate increase of a few beats per minute from the glucagon component
- ▪Appetite suppression severe enough to make hitting protein targets difficult
- ▪Fatigue, especially during escalation steps
- ▪Gallstones and hair shedding at rapid rates of weight loss
- ▪Lean mass loss without deliberate protein intake and resistance training
- ▪Acute pancreatitis — uncommon but a recognised incretin-class risk; severe persistent upper abdominal pain radiating to the back means stop the drug and get assessed
- ▪Markedly delayed gastric emptying — hold the drug before any surgery, endoscopy or procedural sedation and tell the anaesthetist, because of retained gastric contents and aspiration risk
Do not use if
- ▪Personal or family history of medullary thyroid carcinoma or MEN2
- ▪Prior pancreatitis
- ▪Pregnancy or breastfeeding
- ▪Uncontrolled tachyarrhythmia or unstable cardiac disease, given the heart rate effect
- ▪Severe gastroparesis
Evidence level — Human trials
Controlled human clinical data exists.
Not approved in any country; survodutide is an investigational phase 3 drug and everything available to individuals is unlicensed research-chemical material.
Commonly run with
Survodutide FAQ
How does it compare to tirzepatide or retatrutide?+
Tirzepatide is GIP/GLP-1, survodutide is glucagon/GLP-1, and retatrutide is all three. On headline weight loss survodutide's phase 3 numbers land below tirzepatide's, but its liver and visceral fat data are its strongest suit. There is no direct head-to-head against either.
Why is the nausea worse than on semaglutide?+
The glucagon arm adds to the GI load. The phase 2 obesity trial escalated over a single 20-week schedule and still had gastrointestinal adverse events in 75% of survodutide recipients, with only 60% completing the 46 weeks. The phase 2 type 2 diabetes trial concluded outright that dose-related GI adverse events could be mitigated with slower dose escalation. Escalate no faster than every four weeks and hold whenever symptoms persist.
Can I run it with another incretin?+
Stacking survodutide on top of semaglutide, tirzepatide or retatrutide compounds GI adverse events and severe appetite suppression with no data behind it. Cagrilintide is the only sensible partner because it works through the amylin pathway rather than another incretin receptor.
Does the glucagon component raise blood sugar?+
Not net — the GLP-1 arm offsets it, and trials in type 2 diabetes showed HbA1c reductions comparable to semaglutide. Glucose can drift slightly during early low-dose weeks before the GLP-1 effect is fully established.
References
- 1.Glucagon and GLP-1 receptor dual agonist survodutide for obesity: a randomised, double-blind, placebo-controlled, dose-finding phase 2 trial — The Lancet Diabetes & Endocrinology (2024) PMID 38330987
- 2.A Phase 2 Randomized Trial of Survodutide in MASH and Fibrosis — The New England Journal of Medicine (2024) PMID 38847460
- 3.BI 456906: Discovery and preclinical pharmacology of a novel GCGR/GLP-1R dual agonist with robust anti-obesity efficacy — Molecular Metabolism (2022) PMID 36356832
- 4.Baseline characteristics in the SYNCHRONIZE-2 randomized phase 3 trial of survodutide, a glucagon receptor/GLP-1 receptor dual agonist, for obesity in people with type 2 diabetes — Diabetes, Obesity and Metabolism (2026) PMID 41216778
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