Adding glimepiride to insulin plus metformin in type 2 diabetes of more than 10 years' duration-A randomised, double-blind, placebo-controlled, cross-over study

Aims: To investigate the effect on glycaemic control of adding glimepiride to on-going treatment with metformin and insulin in patients with known diabetes more than 10 years. Methods: Glimepiride 4 mg or placebo was added in randomised order for three months with a washout period of 6 weeks. All insulin regimens were allowed. Insulin doses were reduced if considered necessary. Continuous glucose monitoring was performed at the end of each period. Results: Forty-three patients, median age 66 years (46-74), diabetes duration 16 (10-30), BMI 30 kg/m(2) (25-37) and mean HbA(1c) 7.1% NGSP, (64 mmol/mol IFCC) were randomised. With placebo there was no change in HbA(1c) while a decrease of 0.6%, (7 mmol/mol IFCC) (P < 0.001), was observed with glimepiride even though insulin doses had to be reduced in 23 patients (median change 29%, range 2-100%). Minor hypoglycaemia was reported but no severe hypoglycaemic event was observed. The ratio between C-peptide/glucose increased significantly (P < 0.001) with glimepiride, both fasting and postprandially and, in a stepwise multiple regression analysis of possible predictive factors for response, a more pronounced decrease in HbA(1c) was associated with the magnitude of the increment in C-peptide/glucose. Older age was associated with a smaller response. Twenty-nine patients (67%) were defined as responders if this was defined as an HbA(1c) decrease >= 0.5% (5 mmol/mol IFCC) or an insulin dose reduction >= 20%. Conclusions: Even after long duration of diabetes, addition of glimepiride to insulin and metformin can be effective in lowering HbA(1c) and/or reducing the need for exogenous insulin. (C) 2014 Elsevier Ireland Ltd. All rights reserved.