Triple fixed-dose combination empagliflozin, linagliptin, and metformin for patients with type 2 diabetes
Creators: name: Lingvay, Ildiko
name: Beetz, Nadine
name: Sennewald, Regina
name: Schuler-Metz, Annette
name: Bertulis, Julia
name: Loley, Christina
name: Lang, Benjamin
name: Lippert, Caroline
name: Jisoo Lee
name: Manning, Linda Shapiro
name: Terada, Derek
Publisher: name: Taylor & Francis
Year: 2020
Subjects: subject: Biochemistry
subject: Genetics
subject: FOS: Biological sciences
subject: FOS: Biological sciences
subject: Pharmacology
subject: 39999 Chemical Sciences not elsewhere classified
subject: FOS: Chemical sciences
subject: FOS: Chemical sciences
subject: Cancer
subject: Science Policy
subject: 60506 Virology

description: 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. 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<sub>max</sub>) 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<sub>max</sub> for each component within 80.00–125.00%. 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. 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. 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. 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. 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. 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