Use of Concurrent Anti-diabetes Medications in Patients With Type 2 Diabetes in Clinical Practice in the United States.

PURPOSE: This report describes the use of combination therapy in patients with type 2 diabetes mellitus (T2DM) who had been initially prescribed metformin in the United States. METHODS: Retrospective claims data from a de-identified database were used to identify individuals aged ≥18 years with ≥1 claim for a metformin-containing regimen dated between January 1, 2018, and December 31, 2018. Demographics, insurance type, and prescriber type were compared among subgroups receiving two (dual) or three or more (triple+) anti-diabetes therapies. All analyses were descriptive; no formal comparisons were conducted. FINDINGS: Data from 353,062 patients were included. Demographic and other baseline characteristics were similar between the groups receiving dual or triple+ therapy (n = 213,871 and 139,191, respectively). A small age difference was observed between patients receiving dual versus triple+ therapy (mean [SD], 66.5 [11.8] and 65.8 [10.8] years, respectively). Mean (SD) glycosylated hemoglobin levels were lower among patients receiving dual therapy versus triple+ therapy: 7.6% (1.7) versus 8.0% (1.7). The most frequent combination was metformin plus a sulfonylurea (33.4%). The percentage receiving combination therapy with newer treatments was relatively low, and slightly greater in younger patients. Total health care costs were similar with dual and triple+ therapies. IMPLICATIONS: The current descriptive analysis demonstrated generally similar features, with regard to the evaluated factors, in cohorts receiving dual versus triple+ T2DM therapy. However, differences between unmeasured factors could exist and require further evaluation. These findings, based on data from a cohort of patients from clinical practice who had initially been prescribed metformin, provide a useful snapshot of current prescribing practices and can be used to inform future research and evidence-based policy decisions.

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 (Cmax) 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 Cmax 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.