Comparison of the effects on glycaemic control and β-cell function in newly diagnosed type 2 diabetes patients of treatment with exenatide, insulin or pioglitazone: a multicentre randomized parallel-group trial (the CONFIDENCE study).

OBJECTIVE:Progressive β-cell dysfunction hinders the maintenance of glycaemic control in type 2 diabetes, but comparative data on β-cell-protective therapies are lacking in the early stage of type 2 diabetes. Here we evaluated the comparative glycaemic efficacy and impact on β-cell function of three antihyperglycaemic agents that have a β-cell-protective effect, exenatide, insulin and pioglitazone, in newly diagnosed patients with type 2 diabetes. DESIGN AND METHODS:In this 48-week, multicentre, parallel-group study, 416 patients newly diagnosed with type 2 diabetes were randomly assigned 1 : 1 : 1 to receive exenatide, insulin or pioglitazone. The primary end-point was the change in glycosylated haemoglobin (HbA1c) from baseline. Secondary end-points included effects on weight, blood pressure, lipid profiles and β-cell function assessed by homeostasis model assessment, fasting proinsulin:insulin (PI/I), disposition index (DI) and acute insulin response (AIR). RESULTS:At week 48, mean [95% confidence interval (CI)] HbA1c changes from baseline were -1.8% (-1.55% to -2.05%) with exenatide, -1.7% (-1.52% to -1.96%) with insulin and -1.5% (-1.23% to -1.71%) with pioglitazone. Treatment differences were -0.20% (95% CI -0.46% to 0.06%) for exenatide versus insulin (P = 0.185), and -0.37% (95% CI -0.63% to -0.12%) for exenatide versus pioglitazone (P = 0.002). Significant improvements from baseline in AIR, PI/I and DI were observed with all treatments, with the greatest improvements in DI, as well as weight, blood pressure and lipid profile, observed with exenatide. CONCLUSIONS:All three agents showed efficacy regarding glycaemic control and metabolic benefits; however, exenatide showed the greatest efficacy. β-cell function improved in all treatment groups; hence, early initiation of β-cell-protective therapy may halt the decline in β-cell function in type 2 diabetes.