Combined metformin and insulin therapy for patients with type 2 diabetes mellitus

Objective: This study was undertaken to assess the effects of combined trea tment with insulin and metformin in patients with type 2 diabetes mellitus in whom dietary measures, weight control, and oral antihyperglycemic therap y had failed. Background: Insulin resistance in peripheral tissues, increased hepatic glu coneogenesis, and impaired insulin secretion are the underlying factors in the development of type 2 diabetes. Metformin is a biguanide antihyperglyce mic agent that increases peripheral insulin sensitivity, reduces hepatic gl uconeogenesis, and decreases intestinal glucose absorption. Methods: Thirty-one patients (24 women, 7 men; mean age, 61.8 years; mean b ody mass index [BMI], 28.0 kg/m(2)) were enrolled in this randomized, doubl e-blind, 2-way, crossover, placebo-controlled study. Patients with type 2 d iabetes who were treated previously with insulin or oral hypoglycemic agent s and who had a glycosylated hemoglobin (HbA(1c)) level >9% or a fasting bl ood glucose level >8 mmol/L were included. Patients who were being treated with oral agents were switched to insulin therapy and required to maintain stable blood glucose control for 2 months prior to randomization. Patients received insulin plus either metformin 1700 mg/d or placebo for 5 months, f ollowed by a 2-month washout period, and were then crossed over to the othe r treatment arm for 5 months of additional treatment (total treatment perio d: 12 months). Results: Thirty patients completed the study; 1 patient withdrew early beca use of hypoglycemia. Compared with placebo, metformin produced significant reductions from overall baseline in mean daily insulin dose requirement (-8 .69 units [17.2%], P < 0.001), HbA(1c) level (-0.74 [9.9%], P = 0.005), ser um fructosamine level (-44.40 mu mol/L, P = 0.026), 24-hour blood glucose p rofile (P = 0.008), and total cholesterol level (-0.42 mmol/L, P = 0.005). No treatment effects were observed on body weight, blood pressure, serum hi gh-density lipoprotein cholesterol levels, or serum triglyceride levels. Th ere was no correlation between BMI and reduction in HbA(1c). No major side effects were reported. Conclusions: Combination therapy with metformin and insulin improves glycem ic control and reduces insulin requirements, with no major side effects,, i n patients with type 2 diabetes and may improve the risk profile in this pa tient population.