Combination therapy with insulin-independent sodium-glucose cotransporter 2 inhibitors and thiazolidinedione drugs, such as lobeglitazone, has been reported to elicit potential additive efficacy in glycemic control in type 2 diabetes mellitus. This study was conducted to evaluate the pharmacokinetic (PK) drug–drug interactions between empagliflozin and lobeglitazone in healthy subjects.
A randomized, open-label, multiple-dose study was conducted in 30 healthy subjects using a three-treatment, six-sequence, three-way crossover design. Subjects received one of the following treatments once daily for 5 days in each period: 25 mg empagliflozin, 0.5 mg lobeglitazone sulfate, or a combination. Serial blood sampling before every dose and up to 24 h after the last dose was performed during each treatment period. The PK parameters were estimated using noncompartmental methods with the plasma empagliflozin and lobeglitazone concentrations. The absence of a PK interaction was construed as the 90% confidence interval (90% CI) of maximum concentration at steady state (C max,ss) and area under the concentration-time curve over the dosing interval (AUC tau) for combination therapy-to-monotherapy ratios within the limits of 0.80–1.25.
The steady-state plasma empagliflozin and lobeglitazone concentration-time profiles of combination therapy and monotherapy were comparable in the 25 subjects who completed the study. Coadministration of empagliflozin with lobeglitazone did not affect empagliflozin PK (with 90% CIs of 0.956–1.150 and 0.945–1.133 for C max,ss and AUC tau, respectively). Likewise, empagliflozin did not affect lobeglitazone C max,ss or AUC tau (with 90% CIs of 0.869–0.995 and 0.851–1.018, respectively). All treatment groups tolerated mild adverse events well.