Triple fixed-dose combination empagliflozin, linagliptin, and metformin for patients with type 2 diabetes

Objectives: Fixed-dose combination (FDC) 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), empagliflozin, a sodium-glucose co-transporter 2 inhibitor, and linagliptin, a dipeptidyl peptidase-4 inhibitor, versus corresponding free tablet combinations. Methods: Two randomized, open-label, two-way crossover studies in healthy adults compared: 2 FDC tablets of empagliflozin 5 mg/linagliptin 2.5 mg/metformin XR 1000 mg (Study 1; N = 30), 1 FDC tablet of empagliflozin 25 mg/linagliptin 5 mg/metformin XR 1000 mg (Study 2; N = 30) versus corresponding dose of free combinations. Subjects received study medication under fed conditions; washout was >= 35 days between treatments. Primary endpoints: area under the plasma concentration-time curve (AUC) from time 0 to last quantifiable data point for empagliflozin and metformin; AUC from time 0 to 72 hours for linagliptin, and peak plasma concentration (C-max) for empagliflozin, linagliptin, and metformin. Bioequivalence was defined as adjusted geometric mean ratios (FDC: free combination) and two-sided 90% confidence intervals (CIs) of AUC and C-max for each component within 80.00-125.00%. Results: Study 1: 27/29 and 28/30 treated participants were included in the pharmacokinetic analysis for the FDC and free combination periods, respectively. Study 2: 29/29 treated participants were included in the pharmacokinetic analysis for both periods. The adjusted geometric mean ratios of FDCs to their respective free tablet combinations and two-sided 90% CIs were all within the predefined range. The shapes of the mean plasma concentration-time profile of empagliflozin, linagliptin, and metformin XR were similar for subjects in the FDC and free combination groups in both studies. No serious adverse events were reported. Conclusion: 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. PLAIN LANGUAGE SUMMARY: Study supports the convenience of empagliflozin, linagliptin, and metformin XR in 1 tablet as new treatment for type 2 diabetes What is the purpose of this summary? This summary is to help you understand findings from recent research. This summary is about 2 studies that are part of a larger group of studies with these medications. Researchers look at many studies to understand whether a medication works, how it works, and whether it is safe to prescribe to patients. What is known? People with type 2 diabetes often need several medicines to control their blood sugar. Some people find it difficult to take a lot of different tablets, and some people may not want to. This can lead to difficulties with managing type 2 diabetes. Combining medicines into 1 tablet may help make it easier to take the treatment and to manage type 2 diabetes, which gives people more choices. What is new? The combination of empagliflozin, linagliptin, and metformin extended-release (metformin XR for short) in 1 tablet is approved for type 2 diabetes. This combination could help people take all the treatments and better manage their type 2 diabetes. See Figure 1 for a full infographic version of this summary