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Survodutide

Weight Management

Also known as: BI 456906, BI-456906

Half-life: ~80-90 hours (once-weekly dosing)

Last reviewed:  ·  Published:

Weight LossFat Loss

Overview

Survodutide is an investigational, once-weekly subcutaneous peptide developed by Boehringer Ingelheim in partnership with Zealand Pharma. It is a co-agonist of the GLP-1 receptor and the glucagon receptor — combining the appetite-suppressing and insulin-sensitizing effects of GLP-1 with the energy-expenditure and lipolytic effects of glucagon. The dual mechanism aims to drive larger weight loss than single-agonist GLP-1 drugs like semaglutide while also providing meaningful improvements in liver fat and metabolic markers.

In the phase 2 obesity trial published in 2024 (NEJM), survodutide produced mean weight loss of approximately 19% over 46 weeks at the highest dose, with most participants still losing weight at week 46 — suggesting headroom for further losses with longer treatment. Phase 3 obesity (SYNCHRONIZE) and MASH/NASH (LIVERAGE) programs are ongoing as of 2026.

Because survodutide engages the glucagon receptor in addition to GLP-1, it has shown notable improvements in MASH/NASH endpoints in mid-stage trials — driving liver fat reduction beyond what pure GLP-1 agonists achieve. The same dual action can produce a transient rise in heart rate and modest increases in fasting glucose at lower doses before the GLP-1 effect dominates, which is why titration schedules are slow and methodical.

History

Survodutide was developed through the Boehringer Ingelheim / Zealand Pharma collaboration announced in 2011, which focused on next-generation incretin co-agonists. It entered human trials in the late 2010s, with phase 1 PK/PD work showing a half-life suitable for weekly dosing and clean target engagement.

The 2024 phase 2 obesity readout drew significant attention because the placebo-adjusted weight loss figures (~19%) were competitive with tirzepatide and ahead of semaglutide at comparable timepoints. In parallel, phase 2 results in MASH/NASH demonstrated histological improvement in fibrosis — a notoriously difficult endpoint. Both the obesity (SYNCHRONIZE-1, SYNCHRONIZE-2) and MASH (LIVERAGE-1) phase 3 programs are reading out in 2026-2027.

Effects

  • Substantial weight loss (~14-19% at highest doses in phase 2)
  • Suppresses appetite and slows gastric emptying via GLP-1
  • Increases energy expenditure via glucagon receptor activation
  • Reduces liver fat (notable MASH/NASH activity)
  • Improves glycemic control and fasting glucose
  • Lowers LDL cholesterol and triglycerides

Side Effects

  • Nausea (most common, dose-dependent)
  • Vomiting
  • Diarrhea or constipation
  • Decreased appetite
  • Transient heart rate increase (5-10 bpm)
  • Injection site reactions
  • Mild fasting glucose elevation at low doses (resolves with titration)
  • Risk of gallbladder issues with rapid weight loss

Tolerability

Tolerability follows the typical incretin pattern: GI side effects dominate, peak during dose escalation, and ease as the body adapts. The glucagon component adds two unique signals — a modest heart rate bump and a small transient increase in fasting glucose at sub-therapeutic doses — both of which resolve as the GLP-1 effect dominates at higher doses. Slow, methodical titration over 12-16 weeks substantially reduces discontinuation. No serious safety signals have emerged in phase 2; phase 3 will provide definitive cardiovascular and pancreatitis data.

Dosing Ranges

Obesity (phase 2/3 protocol)

Dose Range

0.3-6.0 mg

Frequency

Once weekly SubQ (titrated)

Duration

Long-term (chronic dosing)

MASH / NASH (phase 2)

Dose Range

1.2-6.0 mg

Frequency

Once weekly SubQ (titrated)

Duration

48 weeks minimum

Type 2 diabetes (phase 2)

Dose Range

0.3-4.8 mg

Frequency

Once weekly SubQ

Duration

Long-term

Dosing information is for educational purposes only. Consult a healthcare professional before using any peptide.

Reconstitution

Preparation Details

Typical Vial Size

10 mg

Water Type

Bacteriostatic water (BAC water)

Mixing Volume

2 mL

Half-Life

~80-90 hours (once-weekly dosing)

Molecular Weight

~4700 Da

Reconstitute a 10mg vial with 2mL of BAC water. Store refrigerated at 2-8°C and use within 28 days. Avoid freezing or shaking. Inject slowly down the side of the vial — do not spray directly onto the powder.

Calculate Survodutide dose

Where to buy Survodutide

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Regulatory Status

FDA Status

Not FDA approved. Investigational compound in phase 3 clinical trials for obesity and MASH/NASH.

Legal Status

Unregulated research chemical. Not approved as a drug or dietary supplement in any jurisdiction.

USA

Not approved

Phase 3 trials ongoing (SYNCHRONIZE for obesity, LIVERAGE for MASH)

EU

Not approved

EMA evaluation pending phase 3 readout

UK

Not approved

MHRA evaluation pending phase 3 readout

Australia

Not approved

TGA has not evaluated

Canada

Not approved

Health Canada has not authorized

Cited Studies

Survodutide in Adults with Obesity and without Type 2 Diabetes (Phase 2)

le Roux CW, Steen O, Lucas KJ, Startseva E, Unseld A, Hennige AM

The Lancet Diabetes & Endocrinology (2024)

Phase 2 trial demonstrating ~19% mean weight loss at 46 weeks at the highest dose (4.8 mg weekly), with continued weight reduction at trial end — suggesting further losses possible with longer treatment.

View Study →

Survodutide for Treatment of Metabolic Dysfunction-Associated Steatohepatitis (Phase 2)

Sanyal AJ, Bedossa P, Fraessdorf M, Neff GW, Lawitz E, Bugianesi E

New England Journal of Medicine (2024)

Phase 2 MASH trial showing histological improvement without worsening of fibrosis in 83% of participants at the highest dose, with significant reductions in liver fat content on MRI-PDFF.

View Study →

Pharmacological characterization of BI 456906, a novel glucagon receptor/GLP-1 receptor dual agonist

Bossart M, Wagner M, Elvert R, Evers A, Hennig D, Kannt A

Cell Metabolism (2022)

Preclinical pharmacology paper characterizing survodutide’s dual-receptor binding profile, demonstrating balanced agonism at both receptors and superior weight loss versus single-agonist comparators in obese rodent models.

View Study →

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