Sitagliptin add-on to low dosage sulphonylureas: efficacy and safety of combination therapy on glycaemic control and insulin secretion capacity in type 2 diabetes
International Journal of Clinical Practice, 04/23/2012
Harashima SI et al. – 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.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.
- 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/m2 (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.