OBJECTIVE -The aim of this study was to demonstrate the superiority of benfluorex over placebo as an add-on therapy in type 2 diabetic patients in whom diabetes is insufficiently controlled by sulfonylurea monotherapy and who have a limitation for the use of metformin.RESEARCH DESIGN AND METHODS -Type 2 diabetic patients with HbA 1c (A1C) (7-10%) who were receiving the maximum tolerated sulfonylurea dose and had a contraindication to or poor tolerance of metformin were randomly assigned (double blind) to receive benfluorex 450 mg/day (n ϭ 165) or placebo (n ϭ 160) for 18 weeks. The main efficacy criterion was A1C, analyzed as the change from baseline to the end of treatment using ANCOVA with baseline and country as covariates. Secondary criteria were fasting plasma glucose (FPG), insulin resistance, and plasma lipid level.RESULTS -Both groups were similar at baseline in the intention-to-treat population. A1C significantly decreased with benfluorex from 8.34 Ϯ 0.83 to 7.52 Ϯ 1.04% (P Ͻ 0.001) and tended to increase with placebo from 8.33 Ϯ 0.87 to 8.52 Ϯ 1.36% (NS), resulting in a mean adjusted difference between groups of Ϫ1.01% (95% CI Ϫ1.26 to Ϫ0.76; P Ͻ 0.001). The target A1C (Յ7%) was achieved in 34% of patients receiving benfluorex versus 12% of patients receiving placebo. Significant between-group differences in favor of benfluorex were observed for mean FPG (Ϫ1.65 mmol/l) (P Ͻ 0.001) and for homeostasis model assessment of insulin resistance. Overall tolerance was similar in both groups. Serious adverse events were more frequent in the benfluorex group, without evidence of causality relationship.CONCLUSIONS -Benfluorex as an add-on therapy was superior to placebo in lowering A1C with a between-group difference of 1% in type 2 diabetic patients whose disease was insufficiently controlled with sulfonylurea alone and in whom metformin was contraindicated or not tolerated.
Diabetes Care 29:515-520, 2006T he incidence and progression of microvascular complications in type 2 diabetes are strongly associated with the degree of hyperglycemia. Following the results of the U.K. Prospective Diabetes Study (UKPDS) in 1998, recommended target values for HbA 1c (A1C) in type 2 diabetes were reduced from 7 to 6.5% or even lower (1,2). To achieve such goals, early initiation of combined therapy is being recognized as desirable in type 2 diabetes. According to the pathophysiological mechanism of the disease, the combination of an insulin secretagogue with an insulin sensitizer is the most common drug treatment proposed for type 2 diabetic patients, in addition to diet, lifestyle counseling, and exercise. Insulin sensitizers are not a homogenous drug class. For many years, metformin was the only drug of this type on the market; now thiazolidinediones are an alternative. Both metformin and thiazolidinediones have limitations on their use: gastrointestinal intolerance is common with metformin, and although serious complications such as lactic acidosis are very infrequent, caution should be exercised in patients with cardiova...