Orforglipron

Orforglipron (LY3502970) (Compound 67) is an orally active agonist for Glucagon-like peptide-1 receptor (GLP-1R), which exhibits potency in ameliorates the type 2 diabete^[1]. IC50 & Target:GLP-1 receptor^[1] In Vitro: Orforglipron is an incretin secreted from L cells of the small intestine when nutrients pass through the digestive tract, and glucose is transmitted via the GLP-1 receptor. Orforglipron exhibits various actions such as dependent gastric emptying delay, and feeding suppression^[1]. In Vivo: Orforglipron (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 decreases blood glucose in cynomolgus monkey model^[1].
Orforglipron (0.05-1.35 mg/kg, i.g.) reaches C_max 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 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