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Survodutide is a dual glucagon/glucagon-like peptide 1 (GLP1) receptor agonist. Survodutide has demonstrated blood sugar lowering efficacy in a Phase II trial for the treatment of patients with type 2 diabetes and obesity and was associated with clinically meaningful weight loss[1]. Survodutide is also being studied for the treatment of metabolic dysfunction-associated steatohepatitis (MASH)[2]. | [in vivo]
Survodutide (BI 456906; 3, 10, 20, 30 nmol/kg; SC; daily; 30 days) achieves a greater bodyweight-lowering efficacy in diet-induced obese mice compared with maximally effective doses of Semaglutide (HY-114118; 20, 100 nmol/kg). Survodutide dose-dependently reduces plasma glucagon[1].
Survodutide (1, 3, 10, 30, 100 nmol/kg; SC; single dose) dose-dependently reducesacute food intake in WT but not in GLP-1R KO mice (Three-week-old, male, lean NMRI outbred mice)[1].
Survodutide (1, 3, 10, 30, 100 nmol/kg; SC; single dose) engages the glucagon receptor in vivo upon single dosing, increases liver nicotinamide N-methyltransferase mRNA, and reduces plasma serine and glutamine[1].
Survodutide (SC injection) causes mean residence times of 44 and 140 h and Tmax values of 7 and 51 h obtained in mice and dogs, respectively[1].
Pharmacokinetic Parameters of Survodutide (BI 456906) in mice and dogs[1].
| Mice (20 nmol/kg; SC) | Dogs (10 nmol/kg; SC) | | Tmax (h) | 7 | 50.7 | | Cmax (nM) | 84.9 | 62.0 | | AUC0-∞ (nM?h) | 4640 | 9540 |
| Animal Model: | Male C57BL6/J mice pre-fed with a 60% HFD (22 weeks)[1] | | Dosage: | 3, 10, 20, 30 nmol/kg | | Administration: | SC; daily; 30 days | | Result: | Dose-dependently reduced bodyweight from baseline by up to 32% at Day 28 at a dose of 30 nmol/kg.
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| [References]
[1] BRIAND F, AUGUSTIN R, WESCHE F, et al. 1635-P: Survodutide Weight Loss Is Associated with Changes in Food Preference and Improvement of Dyslipidemia in the Free Choice Diet–Induced Obese Hamster Model[J]. Diabetes, 2024, 33 2. DOI:10.2337/db24-1635-p.
[2] Efficacy, tolerability and pharmacokinetics of survodutide, a glucagon/glucagon-like peptide-1 receptor dual agonist, in cirrhosis[J]. Journal of Hepatology, 2024, 81 5: Pages 837-846. DOI:10.1016/j.jhep.2024.06.003.
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