Extended-release metformin hydrochloride. Single-composition osmotic tablet formulation.

In the new oral, once-daily, extended-release (ER), single-composition osmotic tablet formulation of the biguanide metformin hydrochloride (metformin XT), metformin is released at a controlled rate from a central osmotic tablet core through a semipermeable coating. A decrease in fasting plasma insulin, a marker of insulin resistance, was seen with metformin XT but not with immediate-release (IR) metformin in one well designed trial, but changes were similar in another. The pharmacokinetics of metformin XT reflect its extended-release characteristics. While the bioavailability (in terms of area under the plasma concentration-time curve) of metformin XT taken after the evening meal is similar to that of the IR formulation taken in divided doses, time to peak plasma concentrations is prolonged. Increases in metformin XT dose from 1000mg to 2500mg resulted in predictable and consistent dose-associated increases in metformin exposure. As with other ER metformin formulations, the bioavailability of metformin XT is increased after food, in contrast to the slight decrease seen with the IR formulation. The efficacy of metformin XT 1000, 1500, 2000, or 2500mg once daily with the evening meal was found not inferior to a similar dose range of metformin IR given in divided doses (measured by changes in glycosylated hemoglobin [HbA(1c)]) in a well designed study of 659 evaluable patients with type 2 (non-insulin-dependent) diabetes mellitus previously stabilized on metformin IR. Metformin XT and IR 2000 or 2500 mg/day had clinically similar efficacy (using changes in HbA(1c) and fasting plasma glucose) in another well designed study of 102 evaluable patients with type 2 diabetes. Like the IR formulation, metformin XT is generally well tolerated; gastro-intestinal adverse events are, however, common.