Metformin extended release

▲ Metformin extended release (metformin ER) is a novel gastric-retentive formulation of the antihyperglycemic agent that can be administered once daily. The polymer matrix of the metformin ER 500mg tablet swells in gastric fluid, causing it to be retained in the stomach in the fed state. Over a period of ≈8 hours, the drug dissolves and diffuses through the matrix to be absorbed in the upper gastrointestinal tract. ▲ Systemic exposure to the drug (assessed by the area under the plasma concentration-time curve) with oral metformin ER 1000mg once daily did not differ from that of immediate-release metformin (metformin IR) 1000 mg/day administered as a divided dose. However, the time to maximum plasma concentration was 7.5 hours with metformin ER versus 4.2 hours with metformin IR. ▲ Glycemic control, measured by change from baseline in mean glycosylated hemoglobin (HbA1c) levels at study endpoint, with metformin ER 1500 mg/day (once daily or as divided doses morning and night) or 2000 mg/day (once daily) did not differ from that with metformin IR 1500 mg/day as a divided dose in a 24-week, double-blind, randomized trial in 706 patients with type 2 diabetes mellitus. ▲ In the same study, the American Diabetes Association-recommended HbA1c level of <7% was achieved in significantly more metformin ER 2000 mg/day than metformin IR 1500 mg/day recipients. ▲ Greater glycemic control was seen with metformin ER 1500–2000 mg/day plus glyburide (glibenclamide) than with glyburide plus placebo in a 24-week, double-blind, randomized trial in 575 patients with type 2 diabetes. ▲ Metformin ER is generally well tolerated, with an adverse event profile similar to that of metformin IR. Of interest, the incidence of nausea was significantly lower with metformin ER than with metformin IR in the first week of treatment, suggesting that more rapid dose titration may be possible with metformin ER. The incidence of adverse events with metformin ER 2000 mg/day did not differ from that with metformin IR 1500 mg/day.