Pharmacokinetics of HDM7006, a high-potency balanced GLP-1/GIP dual agonist, in healthy domestic cats

Background HDM7006 is a GLP-1R/GIPR dual agonist developed for body weight management in obese or overweight cats. Objective To Investigate the pharmacokinetic (PK) characteristics of HDM7006 in cats. Animals Forty-eight healthy adult cats were enrolled. Methods In the single-dose PK study, 40 cats were divided into five groups receiving 0.1, 0.5, 1.0 or 2.0 mg/kg (SC) or 1.0 mg/kg (intravenous, IV) of HDM7006, respectively. In the multiple-dose PK study, 8 cats were received 0.5 mg/kg of HDM7006 once weekly for five consecutive doses. Plasma samples were collected before and after drug administration to determine PK parameters and evaluate immunogenicity. Results No gender differences were observed in system exposure of HDM7006 after IV or SC injection. HDM7006 exhibited a low clearance, a low apparent volume of distribution, and a half-life of 43.7 h in cats after IV injection. Following single SC injection, the median T max ranged from 18.0 to 24.0 h, the T 1/2 ranged from 39.8 to 47.1 h, and the bioavailability ranged from 42.23 to 78.38%. Linear PK characteristics were observed within the dose range of 0.1–2.0 mg/kg. Anti-drug antibodies (ADAs) were detected only in one male animal at 336 h post-dose in the 2.0 mg/kg dose group. After five consecutive doses of 0.5 mg/kg, steady state was clearly achieved, and no significant accumulation observed; all ADA test results were negative. Conclusions and clinical importance HDM7006 exhibits predictable, dose-proportional PK and low immunogenicity, supporting a QW SC regimen in cats, and may offer a long-acting therapeutic option for feline weight management and metabolic regulation.