Survodutide
An investigational once-weekly dual GLP-1/glucagon receptor agonist delivering strong weight loss plus a standout liver-fat (MASH) effect.
Survodutide (BI 456906) is a dual GLP-1/glucagon receptor agonist co-developed by Boehringer Ingelheim and Zealand Pharma. It pairs GLP-1-mediated appetite suppression and glucose control with glucagon-driven energy expenditure and direct hepatic fat oxidation. In the SYNCHRONIZE-1 Phase 3 obesity trial it produced roughly 16.6% mean weight loss over 76 weeks, and in a Phase 2 MASH trial up to ~62% of the top-dose arm achieved liver improvement without worsening fibrosis, earning FDA Breakthrough Therapy designation. It is not approved by any regulator as of 2026.
Class
Synthetic dual GLP-1/glucagon receptor agonist peptide
Half-life
~6-7 days (~140-150 hours), supporting once-weekly dosing
Routes
Subcutaneous
Category
Weight Loss & Metabolic
Researched benefits
What it's studied for
Substantial weight loss
The SYNCHRONIZE-1 Phase 3 obesity trial reported approximately 16.6% mean weight loss over 76 weeks at the top dose; earlier Phase 2 data reached as high as ~18.7-19%, placing it near tirzepatide's range.
MASH / liver-fat improvement
In a Phase 2 MASH trial up to ~62% of the 4.8 mg arm achieved histological MASH improvement without worsening of fibrosis (vs 5% placebo), with liver-fat reductions reported up to ~80% in some participants. This is survodutide's clearest differentiator and the basis for its Breakthrough Therapy designation.
Glucagon-driven energy expenditure
The glucagon receptor arm raises resting energy expenditure and stimulates hepatic lipolysis, adding a metabolic lever that pure GLP-1 agonists lack and complementing GLP-1-mediated appetite suppression.
Appetite suppression and glucose control
The GLP-1 component slows gastric emptying, suppresses appetite, and improves glucose-dependent insulin secretion, the mechanism shared with semaglutide and the GLP-1 arm of tirzepatide.
Once-weekly convenience
A ~6-7 day half-life supports once-weekly subcutaneous administration with stepwise dose titration.
Mechanism
How it works
Survodutide is a single peptide that simultaneously activates two receptors: the GLP-1 receptor and the glucagon receptor. The GLP-1 arm works in the classic incretin style, suppressing appetite, slowing gastric emptying, and improving glucose-dependent insulin secretion, which drives the bulk of its weight-loss and glycemic effects.
The differentiating feature is glucagon receptor agonism. On its own glucagon raises blood sugar, but when paired with GLP-1 the net effect is increased resting energy expenditure and direct stimulation of hepatic fat oxidation and lipolysis without the hyperglycemia glucagon alone would cause. This dual balance is what gives survodutide its distinctive metabolic and liver-directed profile.
Mechanistically this places survodutide alongside mazdutide as a GLP-1/glucagon dual agonist, distinct from tirzepatide (GIP + GLP-1) and retatrutide (GIP + GLP-1 + glucagon triple agonist). The glucagon-driven hepatic fat clearance is especially suited to metabolic dysfunction-associated steatohepatitis (MASH), where weight loss alone is often insufficient to resolve liver disease.
The same glucagon axis that provides the benefit also underlies the main mechanistic risk: glucagon receptor activation can raise heart rate and resting energy expenditure, a tradeoff that ongoing Phase 3 trials are characterizing further.
Dosing protocols
Dosing & administration
Dosing reflects protocols reported in research and community literature for educational purposes. It is not medical advice or a recommendation. Most peptides here are not approved for human use.
Reconstitution
Reconstitute the lyophilized powder with bacteriostatic water at the lowest practical volume to maximize concentration. Example: a 5 mg vial + 1 mL BAC water = 5 mg/mL; ~12 units on a 100-unit insulin syringe delivers a 600 mcg starting dose. Refrigerate the reconstituted vial and use within 28 days of mixing.
Beginner
- Dose
- 600 mcg (0.6 mg)
- Frequency
- Once weekly
- Timing
- Same day each week
- Duration
- 4 weeks
- Route
- Subcutaneous
Establish GI tolerance before any titration. This matches the lowest dose studied in Phase 2 (0.6 mg weekly).
Intermediate
- Dose
- 1500-3000 mcg (1.5-3 mg)
- Frequency
- Once weekly
- Timing
- Same day each week
- Duration
- Slow titration over 8-12 weeks from beginner dose
- Route
- Subcutaneous
Step up gradually; the glucagon arm and GI burden make aggressive titration poorly tolerated.
Advanced
- Dose
- 4500-6000 mcg (4.5-6 mg)
- Frequency
- Once weekly
- Timing
- Same day each week
- Duration
- 12-24+ weeks; trial protocols extend to 76 weeks
- Route
- Subcutaneous
Phase 3 trial top-dose range. Requires medical oversight given the substantial GI burden and possible tachycardia at this level.
- Overall studied dose range is roughly 600-6000 mcg (0.6-6 mg) weekly; the Phase 2 obesity program used 0.6 mg through 4.8 mg weekly under clinical supervision.
- Stepwise dose titration is essential to manage gastrointestinal side effects, which cluster during escalation.
- Cycle lengths run 12-24+ weeks per protocol, with clinical trial protocols extending to 76 weeks.
- Survodutide is investigational and not approved for human use; clinical doses were administered under medical supervision. Any use of research-grade material carries unverified identity and concentration risk.
Evidence
Research & clinical studies (3)
SYNCHRONIZE-1: Phase 3 obesity trial of survodutide
In adults with overweight or obesity without diabetes (n=726, 76 weeks), survodutide produced approximately 16.6% mean weight loss at the top dose.
Phase 2 obesity trial of survodutide (dose-finding)
In adults with overweight or obesity (n=387), survodutide produced average weight loss up to ~18.7% at the 4.8 mg dose over 46 weeks.
Phase 2 trial of survodutide in MASH
In participants with MASH (n=295, 48 weeks), up to ~62% of the 4.8 mg arm achieved MASH improvement without worsening of fibrosis versus 5% on placebo, with liver-fat reductions up to ~80% in some participants.
Safety
Side effects & considerations
Commonly reported effects
Contraindications & cautions
- Personal or family history of medullary thyroid carcinoma (MTC) or MEN2 syndrome
- Pregnancy and breastfeeding
- Active pancreatitis
- Severe gastroparesis or active inflammatory bowel disease
The most common side effects are gastrointestinal, generally mild-to-moderate and concentrated during dose escalation, with discontinuation rates comparable to other GLP-1-class compounds. The glucagon component adds heart-rate elevation (possible tachycardia) as a class-specific concern under ongoing Phase 3 evaluation. Class-label serious risks include a rodent thyroid C-cell tumor signal and pancreatitis. Long-term safety data is more limited than for FDA-approved alternatives.
FAQ
Survodutide — common questions
What is survodutide?
Survodutide (BI 456906) is an investigational dual agonist peptide that activates both the GLP-1 receptor and the glucagon receptor. Developed by Boehringer Ingelheim and Zealand Pharma, it is in Phase 3 trials for obesity (SYNCHRONIZE) and MASH.
How does survodutide work?
The GLP-1 arm suppresses appetite and improves glucose control, while the glucagon arm raises resting energy expenditure and drives hepatic fat oxidation directly. That glucagon-mediated liver-fat clearance is the basis for its strong MASH signal and distinguishes it from tirzepatide (GIP + GLP-1) and retatrutide (triple agonist).
How much weight loss does survodutide produce?
The SYNCHRONIZE-1 Phase 3 obesity trial reported roughly 16.6% mean weight loss over 76 weeks at the top dose. Earlier Phase 2 data reached as high as ~18.7-19%, placing it near tirzepatide's range but below retatrutide's.
What is the MASH connection?
Survodutide produced strong Phase 2 liver data, with up to ~62% of the 4.8 mg arm achieving MASH improvement without worsening of fibrosis and liver-fat reductions up to ~80% in some participants. This earned FDA Breakthrough Therapy designation for non-cirrhotic MASH in September 2024.
How is survodutide administered?
It is given as a once-weekly subcutaneous injection with stepwise dose titration. The studied range is roughly 0.6-6 mg weekly. Its ~6-7 day half-life supports weekly dosing.
Is survodutide FDA approved?
No. Survodutide is investigational and not approved by any regulator as of 2026. It holds FDA Breakthrough Therapy designation and Fast Track status for non-cirrhotic MASH, which can speed review but is not approval.
How is survodutide different from mazdutide?
Both are dual GLP-1/glucagon receptor agonists with similar mechanism logic, but they are different molecules from different sponsors: survodutide (BI 456906) from Boehringer Ingelheim, and mazdutide (IBI362) from Innovent Biologics. They are not interchangeable.
What are the side effects?
Primarily gastrointestinal (nausea, vomiting, diarrhea, decreased appetite), consistent with the GLP-1 class and concentrated during titration. The glucagon component adds possible heart-rate elevation, and class-label risks include pancreatitis and a rodent thyroid C-cell tumor signal.
