Exenatide plus metformin compared with metformin alone on β-cell function in patients with Type 2 diabetes

Diabet. Med. 29, 15151523 (2012) Abstract Aim To quantify how much exenatide added to metformin improves beta-cell function, and to evaluate the impact on glycaemic control, insulin resistance and inflammation compared with metformin alone. Methods A total of 174 patients with Type 2 diabetes with poor glycaemic control were instructed to take metformin for 8 +/- 2 months, then they were randomly assigned to exenatide (5 mu g twice a day for the first 4 weeks and forced titration to 10 mu g twice a day thereafter) or placebo for 12 months. At 12 months we evaluated anthropometric measurements, glycaemic control, insulin resistance and beta-cell function variables, glucagon, adiponectin, high sensitivity-C reactive protein and tumour necrosis factor-a. Before and after 12 months, patients underwent a combined euglycaemic hyperinsulinaemic and hyperglycaemic clamp, with subsequent arginine stimulation. Results Exenatide + metformin gave a greater decrease in body weight, glycaemic control, fasting plasma proinsulin and insulin and their ratio, homeostasis model assessment for insulin resistance (HOMA-IR), and glucagon values and a greater increase in C-peptide levels, homeostasis model assessment beta-cell function index (HOMA-beta) and adiponectin compared with placebo + metformin. Exenatide + metformin decreased waist and hip circumference, and reduced concentrations of high sensitivity-C reactive protein and tumour necrosis factor-a. Exenatide + metformin gave a greater increase in M value (+34%), and disposition index (+55%) compared with placebo + metformin; first (+21%) and second phase (+34%) C-peptide response to glucose and C-peptide response to arginine (+25%) were also improved by exenatide + metformin treatment, but not by placebo + metformin. Conclusion Exenatide is effective not only on glycaemic control, but also in protecting beta-cells and in reducing inflammation.