Pharmacokinetics and safety of teneligliptin in subjects with hepatic impairment

Abstract

The pharmacokinetics of teneligliptin was compared in 3 groups of 8 subjects assigned according to their degree of hepatic impairment (mild, moderate, or matched healthy subjects). Hepatic impairment was associated with an increase in maximal plasma concentration (Cmax ) and overall exposure (AUC0-∞ ) to teneligliptin. Geometric least square mean ratios for Cmax in subjects with mild and moderate hepatic impairment were 25% and 38% higher than in healthy subjects, and those for AUC0-∞ were 46% and 59% higher than in healthy subjects, respectively. For both parameters, the upper limit of the 90% confidence intervals was outside the 80%-125% "no effect" limit, but below the FDA-recommended "dose-adjustment" boundary of 200%. The lower mean total clearance in subjects with mild (9.79 L/h) or moderate (8.57 L/h) hepatic impairment resulted in longer mean half-lives (27.9 and 30.9 hours, respectively) than in healthy subjects (clearance: 13.11 L/h, half life: 24.8 hours). Protein binding ranged between 36.9% and 47.5% in subjects with hepatic impairment and between 32.5% and 34.5% in healthy subjects. Overall, teneligliptin was well tolerated by subjects with hepatic impairment. These results may indicate that caution will be needed when administering teneligliptin to subjects with hepatic impairment.

Teneligliptin real-world efficacy assessment of type 2 diabetes mellitus patients in India (TREAT-INDIA study)

“…But dose modification is not required for linagliptin and teneligliptin in patients with renal dysfunction 20,21. Teneligliptin has been studied extensively to assess the pharmacokinetic and safety profile in nondiabetic mild, moderate, and severe renal impairment, and nondiabetic mild to moderate hepatic impairment patients 22,23. Moreover, Otsuki et al and Wada et al studies have confirmed efficacy and safety of teneligliptin in T2DM patients on hemodialysis 24,25…”

Safety and efficacy of teneligliptin in Japanese patients with type 2 diabetes mellitus: a pooled analysis of two Phase III clinical studies

“…Teneligliptin is eliminated via both hepatic metabolism and renal excretion [6,20]. Hepatic impairment was associated with increased exposure to teneligliptin, but within FDA boundaries for requiring dose adjustment [21]. The pharmacokinetics of teneligliptin have also been evaluated in patients with severe renal impairment.…”

Efficacy and safety of teneligliptin

“…This indicates that caution may be needed when administering teneligliptin to subjects with hepatic impairment. [11]…”