Orforglipron hemicalcium hydrate (LY3502970 hemicalcium hydrate; GLP-1 receptor agonist 1 hemicalcium hydrate) is the calcium salt hydrate form of Orforglipron . Orforglipron is an orally active agonist for Glucagon-like peptide-1 receptor (GLP-1R), which exhibits potency in ameliorating the type 2 diabete.
Orforglipron hemicalcium hydrate (0.94-4.8 nM in plasma concentration, i.v., or 0.05-0.1 mg/mL, i.g. for 5 days) suppresses food intake in a dose-dependent manner, promotes insulin secretion and blood glucose reduction in cynomolgus monkey model[1].
Orforglipron hemicalcium hydrate (0.05-1.35 mg/kg, i.g.) reaches Cmax 2 hours after administration at all doses, exhibits proportional ratio of increase in plasma drug exposure to dose increase, indicates a dose-dependent absorption in the gastrointestinal tract[1].
Pharmacokinetic Analysis of Orforglipron hemicalcium hydrate in cynomolgus monkey [1]
| route | Dose (mg/kg) | Tmax (h) | Cmax (ng/mL) | AUC0-24h (ng·h/mL) |
| i.g. | 0.05 | 2.0 | 4.78 | 23.7 |
| i.g. | 0.15 | 2.0 | 20.7 | 135 |
| i.g. | 0.45 | 2.0 | 32.0 | 208 |
| i.g. | 1.35 | 2.0 | 148 | 1040 |
References:
[1]. Pyrazolopyridine derivative having glp-1 receptor agonist effect. WO2018056453A1