Effects of exenatide twice daily versus sitagliptin on 24-h glucose, glucoregulatory and hormonal measures: a randomized, double-blind, crossover study

Aim: To compare exenatide and sitagliptin glucose and glucoregulatory measures in subjects with type 2 diabetes. Methods: An 8-week, double-blind, randomized, crossover, single-centre study. Eighty-six subjects (58% female, body mass index 35 +/- 5 kg/m(2), haemoglobin A1c 8.3 +/- 1.0%) received either exenatide 10 mu g (subcutaneous) twice daily or sitagliptin 100 mg (oral) daily for 4 weeks and crossed to the other therapy for an additional 4 weeks. Main outcome was time-averaged glucose during the 24-h inpatient visits. Results: Both treatments decreased average 24-h glucose, but exenatide had a greater effect [ between-group difference: -0.67 mmol/l, 95% confidence interval (CI): -0.9 to -0.4 mmol/l]. Both treatments decreased 2-h postprandial glucose (PPG), area under the curve of glucose above 7.8 mmol/l (140 mg/dl) and 11 mmol/l (200 mg/dl) and increased the time spent with glucose between 3.9 and 7.8 mmol/l (70 and 140 mg/dl) during 24 h, but exenatide had a significantly greater effect (p < 0.05). Both treatments decreased postprandial serum glucagon, with exenatide having a greater effect (p < 0.005). Both treatments decreased fasting blood glucose to a similar degree (p = 0.766). Sitagliptin increased, while exenatide decreased, postprandial intact glucagon-like peptide-1. Both drugs improved homeostasis model assessment of beta-cell function (HOMA-B), with exenatide having a significantly greater effect (p = 0.005). Both exenatide and sitagliptin decreased 24-h caloric intake, with exenatide having a greater effect (p < 0.001). There was no episode of major hypoglycaemia. Adverse events were mild to moderate and mostly gastrointestinal in nature with exenatide. No study withdrawals were due to an adverse event. Conclusion: Compared to sitagliptin, exenatide showed significantly lower average 24-h glucose, 2-h PPG, glucagon, caloric intake and improved HOMA-B.