NO. 019 · INCRETIN · METABOLIC
GLP-1 / GLUCAGON DUAL AGONIST
Investigational incretin combination
ALIASES
glp1-glucagon-dual-agonist, BI 456906, BI456906
CLASS
GLP-1/glucagon dual receptor agonist (the originator pharma sponsor/Zealand)
FORMULA
Synthetic 29-residue peptide · oxyntomodulin-inspired
SEQUENCE
Modified glucagon backbone with dual receptor selectivity
HALF-LIFE
~7 days (once-weekly)
ROUTES
Subcutaneous (Phase 3 clinical)
MECHANISM OF ACTION
Dual GLP-1 and glucagon receptor agonist developed by the originator pharma sponsor as BI 456906. Combines incretin-driven glycemic control with glucagon-driven thermogenesis. Phase 3 SYNCHRONIZE program targets obesity and NASH simultaneously.
EVIDENCE GRADES
Le Roux 2024 Lancet Diabetes Endocrinol · placebo-subtracted weight loss 14.9% at 4.8 mg/wk in 46-week Phase 2.
Improvement in liver fat fraction + histology endpoints, supporting dedicated NASH Phase 3 program.
SAFETY
Side effects
- GI: nausea, vomiting, diarrhea
- Injection-site reactions
- Tachycardia (modest)
Drug interactions
- Glucagonergic effects may interact with sulfonylureas/insulin
Contraindications
- History of MTC or MEN2
REGULATORY STATUS
FDA · Investigational. Phase 3 SYNCHRONIZE-1/2 obesity trials enrolling.
WADA · Not currently listed on the WADA Prohibited List.
STORAGE
Lyophilized · -20 °C 24 months
Reconstituted · 2-8 °C, 28 days
PEER-REVIEWED EVIDENCE
- Le Roux CW, et al.. Glucagon and GLP-1 receptor dual agonist the GLP-1 / glucagon dual agonist for obesity: a randomised, double-blind, placebo-controlled, dose-finding phase 2 trial. Lancet Diabetes Endocrinol 2024. PMID 38219768. link →
FAQ · 6 QUESTIONS
▶ What is the GLP-1 / glucagon dual agonist?
the GLP-1 / glucagon dual agonist (BI 456906) is a once-weekly GLP-1/glucagon dual receptor agonist developed by the originator pharma sponsor and Zealand Pharma for obesity and NASH/MASH research.
▶ How is it different from the GLP-1 / GIP dual agonist?
the GLP-1 / GIP dual agonist is GLP-1/GIP dual. the GLP-1 / glucagon dual agonist is GLP-1/glucagon dual. The glucagon agonism is hypothesized to drive additional fat oxidation and energy expenditure beyond appetite suppression alone.
▶ What weight loss has Phase 2 shown?
46-week Phase 2 (Le Roux 2024) reported placebo-subtracted weight loss of ~14.9% at the 4.8 mg/wk dose.
▶ Is the GLP-1 / glucagon dual agonist FDA-approved?
Not yet as of 2026-05. Phase 3 SYNCHRONIZE-1 and SYNCHRONIZE-2 trials for obesity are enrolling.
▶ Why combine glucagon agonism with GLP-1?
Glucagon receptor activation increases hepatic lipolysis and energy expenditure; GLP-1 reduces appetite. The combination targets both intake and expenditure, theoretically producing greater fat-mass reduction than GLP-1 monotherapy.
▶ Dose used in trials?
Phase 2 titrated up to 4.8 mg subcutaneously once weekly. This wiki does not recommend any human dose.
SIGNATURE MOVES
Both receptors fire. Enhanced thermogenesis.
Phase 2 NASH endpoints positive. NEJM 2024.
SOURCED FROM GIGACOMPOUNDS
Reference compounds documented on this page are available as research-grade material at GigaCompounds · ≥99% purity · per-batch Certificate of Analysis. For laboratory research use only. No human dose is recommended by this wiki.
▶ LAST UPDATED · 2026-05-19