Pharmacokinetics, Pharmacodynamics and Safety of Janagliflozin in Chinese Type 2 Diabetes Mellitus Patients with Renal Impairment

Background Janagliflozin is a novel sodium–glucose cotransport-2 inhibitor. Despite its remarkable effect in glycemic control, no systematic research has evaluated the effect of renal impairment (RI) on its pharmacokinetics and pharmacodynamics. Methods Here, patients with T2DM ( n = 30) were divided into normal renal function (eGFR ≥ 90 mL/min/1.73 m 2 ), mild RI (eGFR between 60 and 89 mL/min/1.73 m 2 ), moderate RI-I (eGFR between 45 and 59 mL/min/1.73 m 2 ), and moderate RI-II (eGFR between 30 and 44 mL/min/1.73 m 2 ) groups. They were administered 50 mg janagliflozin orally, and plasma and urine samples were collected for the determination of janagliflozin concentration. Results Following oral administration, janagliflozin was rapidly absorbed, with the time to C max of 2–6 h for janagliflozin and 3–6 h for its metabolite XZP-5185. Plasma exposure levels were similar for janagliflozin in T2DM patients with or without RI but decreased for the metabolite XZP-5185 in T2DM patients with eGFR between 45 and 89 mL/min/1.73 m 2 . Janagliflozin significantly promoted the excretion of urinary glucose, even in patients with reduced eGFR. Janagliflozin was well tolerated in patients with T2DM with or without RI, and no serious adverse events (SAEs) occurred during this trial. Conclusions The exposure levels of janagliflozin in T2DM patients were slightly increased with worsening of RI (i.e., 11% increase in the AUC in patients with moderate RI compared with the normal renal function group). Despite worsening of renal function, janagliflozin exerted a significant pharmacologic effect and was well tolerated, even in patients with moderate RI, implying a promising role in the treatment of patients with in T2DM. Registration China Drug Trial register ( http://www.chinadrugtrials.org.cn/I ) identifier no.: CTR20192721.