Aim To quantify how much exenatide added to metformin improves β-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±2months, then they were randomly assigned to exenatide (5μg twice a day for the first 4weeks and forced titration to 10μg twice a day thereafter) or placebo for 12months. At 12months we evaluated anthropometric measurements, glycaemic control, insulin resistance and β-cell function variables, glucagon, adiponectin, high sensitivity-C reactive protein and tumour necrosis factor-α. Before and after 12months, 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 β-cell function index (HOMA-β) 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-α. 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 β-cells and in reducing inflammation.
ASJC Scopus subject areas
- Internal Medicine
- Endocrinology, Diabetes and Metabolism