Sitagliptin add-on to low dosage sulphonylureas: efficacy and safety of combination therapy on glycaemic control and insulin secretion capacity in type 2 diabetes

Aims: To assess the efficacy and safety of combination therapy with sitagliptin and low dosage sulphonylureas on glycaemic control and insulin secretion capacity in Japanese type 2 diabetes. Methods: Eighty-two subjects were sequentially recruited for the 52-week, prospective, single arm study. Sitagliptin was added on to sulphonylureas (glimepride or gliclazide) with or without metformin. The primary endpoint was a change in A1C. The secondary endpoints were changes in BMI, insulin secretion capacity, blood pressure and urinary albumin excretion, unresponsive rate, and hypoglycaemia. Insulin secretion capacity was evaluated by glucagon loading test. Results: Change in A1C was) 0.80% (95% CI) 0.90 to) 0.68) (p < 0.001). Change in BMI, systemic and diastolic blood pressure, and urinary albumin excretion were) 0.38 kg/m 2 (95% CI) 0.72 to) 0.04) (p < 0.05),) 6.7/) 3.6 mmHg (95% CI) 10.0 to) 3.4/) 4.8 to) 2.4) (p < 0.001), and) 43.2 mg/gCr (95% CI) 65.7 to) 20.8) (p < 0.001) respectively. Mild hypoglycaemia was observed in three cases. The unresponsive rate was 6.1%. Glucagon loading test showed that 0- min and 6- min CPR at baseline and 52- week were not significantly changed: 0- min CPR, 1.58 +/- 0.58- 1.71 +/- 0.73 ng/ml; 6- min CPR, 3.48 +/- 1.47- 3.58 +/- 1.21 ng/ml. Insulin secretion capacity, CPI and SUIT index at baseline did not predict the efficacy of the combination therapy. The final dosages of glimepiride and gliclazide were 1.44 +/- 0.90 mg and 34.5 +/- 15.3 mg respectively. The dosage of sitagliptin was increased from 50 mg to 69.0 +/- 24.5 mg in 52- week. Conclusions: The combination therapy with sitagliptin and low dosage sulphonylureas was safe and effective for glycaemic control. Glucagon loading test indicated that 1 year administration of sitagliptin and sulphonylureas preserved insulin secretion capacity.