Pharmacokinetics of a Fixed-Dose Combination of Atorvastatin and Metformin Extended Release versus Concurrent Administration of Individual FormulationsA Randomized, Open-Label, Two-Treatment, Two-Period, Two-Sequence, Single-Dose, Crossover, Bioequivalence Study

Background: Type 2 diabetes mellitus is associated with a 2- to 4-fold increased risk of coronary heart disease (CHD). Combined therapy with an antihyperglycaemic agent and an HMG-CoA reductase inhibitor (statin) is indicated for the treatment of diabetic patients at risk of CHD. Patients with type 2 diabetes are generally considered to be at equivalent cardiovascular disease risk to patients with established CHD, and should have low-density lipoprotein (LDL) cholesterol levels reduced to <100mg/dL or by 30–40%. Atorvastatin is the drug of choice for lowering LDL cholesterol levels. Metformin is the first therapeutic option in type 2 diabetes patients who are overweight or obese because it may also prevent vascular complications and mortality. Hence, a fixed-dose combination (FDC) of atorvastatin 10 mg and metformin 500 mg extended release (ER) was developed for patients with type 2 diabetes with or without hyperlipidaemia. Objectives: This study set out to establish bioequivalence between treatment 1 (test) — atorvastatin/metformin ER 10 mg/500 mg FDC, and treatment 2 (reference) — atorvastatin 10 mg (Lipitor®) and metformin 500 mg (Glucophage® XR) administered concurrently as individual tablets.