Cagrilintide pharmacokinetics, safety, and tolerability unaffected by renal or hepatic impairment

Managing obesity and type 2 diabetes often involves pharmacotherapy, with cagrilintide (an amylin agonist) and its combination with semaglutide (CagriSema) showing promise. For safe and effective drug use, understanding how organ dysfunction affects drug metabolism is critical. Patients with renal impairment or hepatic impairment often require dose adjustments due to altered drug clearance, which can impact efficacy and increase adverse event risk. This study addresses this gap for cagrilintide, ensuring appropriate dosing strategies for diverse patient populations.

Two distinct Phase 1 studies evaluated the impact of organ impairment. In the renal impairment study, 33 adult participants (normal function, n=14; mild, n=7; moderate, n=7; severe, n=5) received a single subcutaneous dose of cagrilintide 0.6 mg. The hepatic impairment study involved 32 adult participants (normal function, n=14; mild, n=7; moderate, n=7; severe, n=4) who received a single subcutaneous dose of cagrilintide 0.9 mg. The primary endpoint for both was the area under the cagrilintide plasma concentration curve (AUC0-∞), measured from baseline to day 36 (renal) or day 39 (hepatic), alongside Cmax and safety assessments.

Both studies demonstrated that total cagrilintide exposure (AUC0-∞), maximum concentration (Cmax), and other pharmacokinetic parameters were largely similar across groups, with no consistent patterns linked to the severity of renal or hepatic impairment. Safety and tolerability profiles were also comparable across all groups. Specifically, for renal impairment:

Compared with normal renal function, the estimated ratio of the mean AUC0-∞ was 1.23 (90% confidence interval [CI], 0.91-1.66) in mild impairment, 1.18 (CI, 0.87-1.59) in moderate impairment, and 1.21 (CI, 0.87-1.68) in severe impairment. For hepatic impairment, the estimated ratio of the mean AUC0-∞ was 0.0.99 (CI, 0.89-1.11) in mild impairment, 1.01 (CI, 0.91-1.12) in moderate impairment, and 1.11 (CI, 0.96-1.30) in severe impairment. These ratios, all close to 1.0 and with CIs spanning 1.0, indicate no clinically significant differences in drug exposure.