Pharmacokinetics, pharmacodynamics and tolerability of single and multiple doses of janagliflozin, a sodium‐glucose co‐transporter‐2 inhibitor, in Chinese people with type 2 diabetes mellitus

Abstract Aims To evaluate the pharmacokinetic (PK) and pharmacodynamic (PD) characteristics, and tolerability of janagliflozin, a novel sodium‐glucose co‐transporter‐2 inhibitor, in Chinese people with type 2 diabetes mellitus (T2DM). Materials and methods In this study, 36 people with T2DM were randomly assigned in a 1:1:1:1 ratio to receive janagliflozin 25 mg, janagliflozin 50 mg, dapagliflozin 10 mg or placebo. Participants received a single dose on day 1, and were treated once daily from day 4 to day 17. Results Following oral administration, janagliflozin was rapidly absorbed, reaching C max at 2 hours. The mean half‐life (t 1/2 ) at steady state was approximately 21 to 23 hours. There was no significant accumulation with multiple doses (accumulation factor < 2). In participants treated with janagliflozin 25 mg, janagliflozin 50 mg, dapagliflozin 10 mg or placebo, change in mean 24‐hour urinary glucose excretion from baseline was 92.35, 94.17, 87.61 and 6.26 g after multiple doses, and change in mean fasting plasma glucose level from baseline to day 17 was −2.18, −2.66, −2.79 and 1.70%, respectively. Most adverse events (AEs) were mild or moderate with no deaths, serious AEs, or discontinuations due to AEs. Conclusions Single and multiple oral administration (14 days) of janagliflozin 25 mg and 50 mg exhibited favourable PK, PD and tolerability profiles in Chinese people with T2DM, which were comparable to those of dapagliflozin 10 mg. Janagliflozin 25 mg and 50 mg are recommended for further clinical investigation.