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 [HbA(1c)] >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, HbA(1c), 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.