No apparent pharmacokinetic interactions were found between henagliflozin: A novel sodium-glucose co-transporter 2 inhibitor and glimepiride in healthy Chinese male subjects.

What Is Known And Objective: Henagliflozin is a novel selective sodium-glucose co-transporter 2 (SGLT2) inhibitor with similar inhibitory effect to ertugliflozin. Glimepiride is widely used to treat type 2 diabetes mellitus (T2DM) with few cardiovascular side effects. In the present study, we aimed at evaluating the pharmacokinetic (PK) interactions between henagliflozin and glimepiride.

Methods: An open-label, single-centre, single-arm, 3-period, 3-treatment, self-control study was conducted in twelve healthy Chinese male subjects. During each study period, subjects received a single oral dose of glimepiride 2 mg, multiple oral doses of henagliflozin 10 mg or a combination of the two drugs. Serial blood samples were collected 24 h post-dosing for PK analyses. Finger-tip blood glucose was also tested for safety evaluation.

Results And Discussion: Co-administration of henagliflozin with glimepiride did not affect their plasma PK profiles. For henagliflozin, the 90% confidence intervals for the geometric mean ratio (GMR) for the maximum plasma concentrations at steady-state (C ) and the area under the plasma concentration-time curve during a dosing interval at steady-state (AUC ) of combination therapy to henagliflozin alone were 1.00 (0.93-1.08) and 1.00 (0.98-1.02), respectively. For glimepiride, the corresponding values of combination therapy to glimepiride alone were 1.00 (0.88-1.13) for maximum plasma concentrations (C ), 0.91 (0.84-0.99) for the area under the plasma concentration-time curve from 0-24 h (AUC ) and 0.91 (0.83-1.00) for the plasma concentration-time curve from 0 h to infinite (AUC ), respectively. All values fell within the equivalence range of 0.8-1.25. All monotherapies and combination therapy led to no serious adverse events and were well tolerated.

What Is New And Conclusion: Multiple doses of henagliflozin did not exert a significant change on glimepiride PK profiles and a single dose of glimepiride had little effect on henagliflozin blood concentration. Thus, henagliflozin can be co-administered with glimepiride without dose adjustment of either drug.