Ildiko Lingvay 1, Nadine Beetz 2, Regina Sennewald 2, Annette Schuler-Metz 3, Julia Bertulis 3, Christina Loley 4, Benjamin Lang 4, Caroline Lippert 3, Jisoo Lee 5, Linda Shapiro Manning 6, Derek Terada 6
Main idea: The evaluated doses of empagliflozin/linagliptin/metformin XR FDC tablets were bioequivalent to the corresponding free combinations. Based on these two bioequivalence studies and existing phase 3 data, the FDA has recently approved this triple FDC to improve glycemic control in adults with T2D.
Objectives: Fixed-dose combination therapy can improve outcomes in type 2 diabetes (T2D) We evaluated the bioequivalence of 2 doses of an FDC of extended-release metformin (metformin XR) and empagliflozin.
Methods: Two randomized, open-label, two-way crossover studies in healthy adults. Subjects received study medication under fed conditions; washout was 35 days between treatments. Primary endpoints were area under the plasma concentration-time curve (AUC) for empagliflozin and metformin and peak plasma concentration (Cmax) for linagliptin and empagsilin. Bioequivalence was defined as adjusted geometric mean ratios (FDC: free combination) and two-sided 90% confidence intervals (CIs) of AUC and Cmax.
Results: Study 1: 27/29 and 28/30 treated participants were included in the pharmacokinetic analysis for the FDC and free combination periods. No serious adverse events were reported. Study 2: 29/29 treated participants also were part of the analysis. The shapes of the mean plasma concentration-time profile of empagliflozin, linagliptin, and metformin XR.