Review: Optimal dosing strategies for maximising the clinical response to metformin in type 2 diabetes

Abstract

Recently revised consensus targets for glycaemic management in patients with type 2 diabetes are challenging and require optimisation of dosing strategies for oral antidiabetic therapies. The demonstration of significant cardiovascular outcome benefits in metformin-treated type 2 diabetic patients enrolled in the United Kingdom Prospective Diabetes Study has established this agent as the first line oral therapy after diet failure in newly presenting overweight people with type 2 diabetes mellitus. The antihyperglycaemic efficacy of metformin increases with increasing daily doses between 500 mg and the upper limits of the recommended daily dosage ( ≥ 2000 mg/day). Although metformin is associated with gastrointestinal side-effects in up to 20% of patients, this is not generally dose related. Transient dose reduction, slower titration and taking the dose with meals may ameliorate the problem. Risk of lactic acidosis due to metformin is negligible when this agent is prescribed correctly, and is unrelated to the plasma metformin concentration. Intensification of metformin therapy within the dose range represents a rational and practical therapeutic strategy for optimising glycaemic control in patients who are suitable for, and tolerant of, metformin treatment. The recently introduced 1000 mg metformin tablet should facilitate the use of higher doses and may help treatment compliance.