Extensively Studied

Survodutide

Dual GLP-1/Glucagon Receptor Agonist | Weight Loss & Diabetes

Survodutide (BI 456906) is an investigational dual glucagon receptor (GCGR) and GLP-1 receptor (GLP-1R) agonist designed for once-weekly subcutaneous administration. This 29-amino acid peptide with C18 fatty acid acylation represents a novel approach to metabolic disease treatment by simultaneously targeting both energy intake reduction (via GLP-1R) and energy expenditure increase (via GCGR), demonstrating robust efficacy in clinical trials for obesity and metabolic dysfunction-associated steatohepatitis (MASH).

Daily dose

0.6-6.0mg

Frequency

Once weekly

Cycle length

24-76+ weeks

Storage

2-8°C

Key benefits

Dual mechanism for superior weight loss, once-weekly dosing, demonstrated efficacy in obesity/MASH/T2D, well-established safety profile from Phase 2/3 trials

How it works

Balanced agonism of glucagon receptors (increases energy expenditure, hepatic fat oxidation) and GLP-1 receptors (reduces appetite, slows gastric emptying) with ~6-day half-life enabling weekly dosing

Dosage protocols

Goal

Obesity - Standard Protocol

Dose

3.6-6.0mg · Once weekly

Route

Subcutaneous (abdomen/thigh)

Goal

Obesity - Conservative Start

Dose

0.6mg titrated over 24 weeks · Once weekly with 4-week intervals

Route

Subcutaneous

Goal

MASH Treatment

Dose

2.4-4.8mg · Once weekly

Route

Subcutaneous

Goal

Type 2 Diabetes

Dose

0.3-2.7mg · Once weekly

Route

Subcutaneous

Research indications

weight Loss

Obesity Without Diabetes — Phase 2 trial showed 14.9% mean weight loss at 46 weeks with 4.8mg dose, 55% achieving ≥15% weight loss

Obesity With Type 2 Diabetes — Superior weight loss vs semaglutide (-8.7% vs -5.3%) at 16 weeks in head-to-head trial

Sustained Weight Management — Dual mechanism addresses both energy intake and expenditure, potentially reducing weight regain

metabolic

Metabolic Dysfunction-Associated Steatohepatitis (MASH) — Phase 2 trial: 62% achieved MASH improvement without fibrosis worsening at 4.8mg dose

Liver Fat Reduction — 63-67% achieved ≥30% liver fat reduction in MASH trial, maintained in cirrhosis patients

Type 2 Diabetes Control — Dose-dependent HbA1c reduction up to -1.6% in Phase 2 trial on metformin background

cardiovascular

Blood Pressure Reduction — Secondary endpoint in Phase 3 trials based on expected cardiovascular benefits from weight loss

Cardiovascular Risk Factors — SYNCHRONIZE-CVOT trial evaluating MACE outcomes in 4,935 high-risk participants

Metabolic Syndrome Components — Improvements in multiple parameters including waist circumference and glycemic control

Administration

injectable

Interactions

Use Caution

Semaglutide/Tirzepatide — Both are GLP-1 receptor agonists - combining may lead to excessive GLP-1 activation and increased gastrointestinal side effects. Not recommended without medical supervision.

Compatible

Metformin — No direct interaction. Can be used together as demonstrated in Phase 2 trials with type 2 diabetes patients on metformin background therapy.

Compatible

SGLT2 Inhibitors — No known interactions. Phase 3 trials allow concurrent use of SGLT2 inhibitors with appropriate monitoring of glycemic control.

Monitor Combination

Sulfonylureas — Risk of hypoglycemia when combined. Monitor blood glucose closely and consider sulfonylurea dose reduction if needed.

Dose Dependent

Insulin — May require insulin dose adjustment due to improved glycemic control. Start with lower insulin doses and titrate based on glucose monitoring.

Requires Timing

Oral Contraceptives — Delayed gastric emptying may affect absorption. Take oral contraceptives at least 1 hour before survodutide injection.

Monitor Combination

Warfarin — May affect warfarin absorption due to delayed gastric emptying. Monitor INR more frequently when initiating or changing survodutide dose.

Avoid Combination

Other Glucagon Agonists — Risk of excessive glucagon receptor activation. Do not combine with other glucagon receptor agonists.

Safety notes

Common GI side effects: nausea (40-66%), diarrhea (25-49%), vomiting (15-41%)

Most GI effects occur during dose escalation - use flexible dosing if needed

Heart rate may increase slightly (mean 2-5 bpm) - monitor if cardiac conditions

Not recommended in pregnancy or breastfeeding - use contraception

No dose adjustment needed for hepatic impairment including cirrhosis

Monitor blood glucose if on diabetes medications - may need adjustment

Research studies

Phase 2 Obesity Trial Without Diabetes (2024)

Human | 0.6-4.8mg weekly | 46 weeks | Up to 14.9% weight loss

In 387 participants with BMI ≥27 kg/m² without diabetes, survodutide 4.8mg achieved mean 14.9% weight loss vs 2.8% placebo. 83% achieved ≥5% weight loss, 69% achieved ≥10%, and 55% achieved ≥15% weight loss.

Phase 2 MASH and Fibrosis Trial (2024)

Human | 2.4-6.0mg weekly | 48 weeks | 47-62% MASH improvement

In 293 participants with biopsy-confirmed MASH and fibrosis F1-F3, survodutide improved MASH without worsening fibrosis in 47% (2.4mg), 62% (4.8mg), and 43% (6.0mg) vs 14% placebo. Liver fat reduction ≥30% occurred in 63-67% of treated patients.

Phase 2 Type 2 Diabetes Trial (2023)

Human | 0.3-2.7mg weekly | 16 weeks | Superior to semaglutide

Head-to-head comparison showed survodutide achieved greater weight loss than semaglutide 1.0mg after 16 weeks (-8.7% vs -5.3%). HbA1c reductions were dose-dependent, reaching -1.6% with highest doses.

Preclinical Pharmacology Study (2022)

Animal/In vitro | Various doses | EC50 0.52nM GCGR, 0.33nM GLP-1R

Demonstrated balanced dual agonism with ~1:1 potency ratio at glucagon and GLP-1 receptors. Half-life of 44 hours in mice and 140 hours in dogs supported once-weekly dosing development.

Related compounds

Tirzepatide Retatrutide Mazdutide Semaglutide