FIXED-DOSE COMBINATION THERAPY IN TYPE 2 DIABETES MELLITUS

Objective: The management of type 2 diabetes mellitus (T2DM) often requires combinations of antihyperglycemic medications with complementary mechanisms of action. Inadequate adherence to combination therapy, possibly related to pill burden (greater number of pills and higher administration frequency) and poor tolerability, may lead to suboptimal clinical outcomes. One potential means of addressing these problems is the use of fixed-dose combinations (FDCs) that simplify the treatment regimen by reducing pill burden compared with the same combination delivered as separate pills. The present study evaluates the efficacy and tolerability of FDCs in the treatment of T2DM patients and provides an overview of dosing, costs, and adherence. Methods: A review of FDCs, with particular attention to those that contain metformin extended-release (XR) and allow once-daily dosing. Results: Many FDCs contain metformin as one of the component drugs. However, the standard immediaterelease (IR) formulation of metformin requires twice-daily dosing and may have tolerability problems related to adverse gastrointestinal (GI) effects. The XR formulations of metformin can be administered once daily and have been shown to reduce the occurrence of GI effects frequently observed with metformin IR; consequently, they may have significant advantages for inclusion in FDCs. The long-term cost-effectiveness of FDCs remains to be fully determined. Conclusion: For patients taking metformin, FDCs containing metformin XR offer equivalent efficacy with reduced dose frequency and, potentially, fewer GI events compared with standard IR formulation, as well as a reduced number of pills compared with separate-pill regimens. By reducing pill burden and improving tolerability, FDCs may improve adherence.