Survodutide

Also known as: BI 456906

Evidence: Clinical

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Overview

Glucagon and GLP-1 receptor dual agonist peptide (BI 456906); in phase 3 SYNCHRONIZE-1, 3.6 and 6.0 mg weekly cut body weight 12.2 to 13.0% vs 5.4% with placebo at 76 weeks.

Survodutide (BI 456906) is a 29-residue glucagon-based peptide from Boehringer Ingelheim with GLP-1 receptor activity built into the glucagon sequence, 1-aminocyclobutane-1-carboxylic acid at position 2 against DPP-4 cleavage, and a C18 diacid on Lys24 for once-weekly subcutaneous dosing (Zimmermann 2022). In a 46-week phase 2 obesity trial (n=386), weight fell 6.2 to 14.9% across 0.6 to 4.8 mg vs 2.8% with placebo (le Roux 2024). In biopsy-confirmed MASH with F1 to F3 fibrosis, 47 to 62% improved without fibrosis worsening vs 14% (Sanyal 2024). Phase 3: 12.2 to 13.0% weight loss vs 5.4% at 76 weeks without diabetes, 8.2 to 9.8% vs 3.9% with type 2 diabetes, and 30% or more liver-fat reduction in 68.5% vs 28.6% in at-risk MASLD. Investigational; no approval in Drugs@FDA.

Benefits

Weight loss (human phase 3 RCTs), reduced liver fat in at-risk MASLD (human phase 3 RCT), MASH improvement without fibrosis worsening (human phase 2 RCT), lower HbA1c in type 2 diabetes (human phase 3 RCT)

Dosing reference

Research dose: 3.6 or 6.0 mg once weekly in phase 3 (SYNCHRONIZE); phase 2 tested 0.6 to 4.8 mg (obesity) and 2.4 to 6.0 mg (MASH)
Range: 2400 to 6000 mcg, 1x weekly
Reconstitution: 2 mL bacteriostatic water
Common vial sizes: 5 mg, 10 mg

Subcutaneous, once weekly. Phase 2 obesity: 20 weeks of dose escalation, then 26 weeks of maintenance (le Roux 2024). Phase 2 MASH: 24-week rapid escalation, then 24 weeks of maintenance (Sanyal 2024). Phase 3 escalated to 3.6 or 6.0 mg and treated for 76 weeks (le Roux 2026; Wharton 2026). No dose adjustment was needed in cirrhosis in a phase 1 PK study (Lawitz 2024).

Mechanism

Survodutide is a dual agonist of the glucagon receptor and the GLP-1 receptor, made by introducing GLP-1 receptor activity into the human glucagon sequence and tuning the balance between the two (Zimmermann 2022). In mice it lowered body weight more than semaglutide, through both reduced food intake and raised energy expenditure; glucagon receptor engagement in the liver is proposed to drive the extra liver-fat reduction (Zimmermann 2022). In people it lowered plasma amino acids and glucagon, read as target engagement at both receptors (Jungnik 2023). A C18 diacid on a glycine-serine linker at Lys24 binds albumin to extend the half-life (Zimmermann 2022).

Evidence

Clinical: at least one published human trial or an approved drug

Phase 1b, up to 16 weeks (n=125): placebo-corrected weight loss up to 13.8%; lower plasma amino acids and glucagon showed target engagement (Jungnik et al., 2023)
Phase 2 obesity, 46 weeks (n=386): -6.2% to -14.9% across 0.6 to 4.8 mg vs -2.8% with placebo; GI events 75% vs 42% (le Roux et al., 2024)
Phase 2 MASH with F1 to F3 fibrosis, 48 weeks (n=293): MASH improvement without fibrosis worsening in 47 to 62% vs 14% with placebo (Sanyal et al., 2024)
Phase 3 SYNCHRONIZE-1, 76 weeks (n=725, no diabetes): -12.2% (3.6 mg) and -13.0% (6.0 mg) vs -5.4% with placebo (le Roux et al., 2026); SYNCHRONIZE-2 with type 2 diabetes (n=752): -8.2% and -9.8% vs -3.9% (Wharton et al., 2026)
Phase 3 SYNCHRONIZE-MASLD, 48 weeks (n=216): 30% or more liver-fat reduction by MRI-PDFF in 68.5% vs 28.6% with placebo, treatment-regimen estimand (Kaplan et al., 2026)
Human-trial status: phase 3 reported for obesity, type 2 diabetes and MASLD; a cardiovascular outcomes trial (SYNCHRONIZE-CVOT) is under way; no approval in Drugs@FDA as of October 2026

References

Side effects

Gastrointestinal events are the main effect: 75% vs 42% on placebo in phase 2 obesity (le Roux 2024); nausea 66%, diarrhoea 49% and vomiting 41% vs 23%, 23% and 4% in phase 2 MASH, with serious adverse events 8% vs 7% (Sanyal 2024); 80.9 to 89.7% vs 47.9% in SYNCHRONIZE-1, mostly mild to moderate. In phase 1b with 6-week escalation, 12.5% stopped, most often for a cardiac or vascular event (7.5%) (Jungnik 2023). No deaths in SYNCHRONIZE-1.

Storage

Storage: Refrigerated (2-8°C); general lyophilised-peptide guidance, no compound-specific CoA located
Lyophilized: 24+ months refrigerated
Reconstituted: 28 days refrigerated (general lyophilised-peptide guidance)

Pharmacology

Half-life: Human value not given in published abstracts; mean residence time 44 h (mouse) and 140 h (dog) after subcutaneous dosing; dosed once weekly in humans
Bioavailability: No figure published; subcutaneous tmax 7 h (mouse) and 51 h (dog) (Zimmermann 2022)
Molecular weight: 4231.7 Da
Sequence: H[Ac4c]QGTFTSDYSKYLDERAAKDFIK[C18 diacid-gamma-Glu-GSGSGG on Lys24]WLESA-NH2