Effects of metformin extended release compared to immediate release formula on glycemic control and glycemic variability in patients with type 2 diabetes

PURPOSE The purpose of this study is to evaluate, in a randomized clinical trial, the effects of metformin immediate release (IR) compared with metformin extended release (XR) on the gastrointestinal tolerability and glycemic control. MATERIALS AND METHODS We enrolled 253 Caucasian patients with type 2 diabetes not well controlled by diet (glycated hemoglobin [HbA1c] >7.0% and <8.5%). Patients were randomized to metformin IR or metformin XR for a period of 6 months at the maximum tolerated dose. The average dose of metformin IR used was 2,000±1,000 mg/day, while that of metformin XR was 1,000±500 mg/day. We evaluated body weight, HbA1c, fasting and postprandial glucose, fasting plasma insulin (FPI) and homeostasis model assessment insulin resistance (HOMA-IR), lipid profile, and levels of some adipocytokines, including tumor necrosis factor-α (TNF-α), high-sensitivity C-reactive protein (hs-CRP), visfatin, and vaspin. Moreover, at the baseline and after 6 months, we administered patients some validated questionnaires to assess patients' satisfaction toward treatments. RESULTS After 6 months, both formulations gave a similar reduction in body weight and body mass index (BMI); however, metformin XR gave a greater improvement in glycemic control, FPI, and HOMA-IR, compared with both baseline and metformin IR. A reduction in total cholesterol (TC) and low-density lipoprotein (LDL) cholesterol was observed with metformin XR compared with IR. Levels of TNF-α, hs-CRP, and vaspin were reduced by metformin XR but not by the IR formulation. Metformin XR also raised the levels of visfatin. CONCLUSION Metformin XR formulation seems to be more effective than metformin IR in improving glyco-metabolic control, lipid profile, and levels of some adipocytokines in patients with type 2 diabetes mellitus.