The extended-release formulation of metformin (MXR) prolongs drug absorption in the
upper gastrointestinal tract and permits once-daily dosing in patients with type 2
diabetes mellitus. This newer formulation may enhance patient compliance with oral
therapy and improve long-term control of diabetes compared with the conventional immediate-release
formulation of metformin (MIR).
The goal of this study was to determine the effects on glycemic control of a switch
to MXR therapy in patients with type 2 diabetes currently treated with MIR.
This was a multicenter, randomized, double-blind, parallel-group study in patients
with established type 2 diabetes. Eligible patients were to have a glycated hemoglobin
(HbA1c) value ≤8.5% and mean fasting plasma glucose (FPG) concentrations ≤200 mg/dL while
receiving MIR 500 mg BID for at least 8 weeks. After a 2-week, single-blind lead-in
period, patients were randomly assigned to receive MXR 1000 or 1500 mg QD for 24 weeks
or to continue MIR 500 mg BID for 24 weeks. The primary efficacy variable was change
in HbA1c from baseline to week 12. Other variables included change in FPG levels; change in
HbA1c; distribution of HbA1c values; mean daily blood glucose concentrations (self-monitored); levels of fructosamine,
serum insulin, and lipids; and body weight.
Two hundred seventeen patients were randomized to treatment. The mean change from
baseline in HbA1c values at weeks 12 and 24 were small and similar in the 3 treatment groups. At week
12, the mean change from baseline in HbA1c was 0.15% for MIR, 0.23% for MXR 1000 mg, and 0.04% for MXR 1500 mg. The corresponding
mean changes at week 24 were 0.06%, 0.25%, and 0.14%.
In this study, patients with type 2 diabetes who had been receiving twice-daily MIR
achieved comparable glycemic control when therapy was switched to once-daily MXR at
the same or a greater total daily dose.