Metabolic effect of repaglinide or acarbose when added to a double oral antidiabetic treatment with sulphonylureas and metformin: a double-blind, cross-over, clinical trial.

摘要

ABSTRACT Objective: To compare the metabolic effects of acarbose and repaglinide in type 2 diabetic patients who are being treated with a sulphonylurea-metformin combination therapy. The primary endpoint of the study was to evaluate which add-on treatment between acarbose and repaglinide is more efficacious in reducing PPG. The second endpoint was to evaluate which of these two treatment is more efficacious in the global management of glucose homeostasis in the enrolled patients. Research design and methods: After a 4-week run-in period with a suplonylurea-metformin combination, 103 patients were randomised to receive in addition either repaglinide, up to 6 mg/day (2 mg three times a day) or acarbose, up to 300 mg/day (100 mg three times a day) with forced titration (independently of their glycaemic control, unless side-effects developed due to the drug dosage) for 15 weeks. The treatment was then crossed-over for further 12 weeks until the 27th week. We assessed body mass index (BMI), glycosylated haemoglobin (HbA(1c)), fasting plasma glucoe (FPG), postprandial plasma glucose (PPG), fasting plasma insulin (FPI), postprandial plasma insulin (PPI), homeostatic model assesssment (HOMA) index, systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides (Tg), at baseline and at 1, 2, 15 and 27 weeks of treatment. Results: Seven patients did not complete the study, comprising one patient who was lost to follow-up and a further six through side-effects (two in week 1, one in week 15 and three after cross-over) Side-effects were classified as nausea (one in acarbose group), gastrointestinal events (four in acarbose group), and hypoglycaemia (one in repaglinide group). After 15 weeks of therapy, the repaglinide-treated patients experienced a significant decrease in HbA(1c) (-1.1%, p < 0.05), FPG (-9.5%, p < 0.05), and PPG (-14.9%, p < 0.05), when compared to the baseline values. However, the same treatment was associated with a significant increase in body weight (+2.3%, p < 0.05), BMI (+3.3%, p < 0.05) and FPI (+22.5%, p < 0.05); The increase was reversed during the cross-over phase. After 15 weeks of therapy, the acarbose-treated patients experienced a significant decrease in body weight (-1.9%, p < 0.05), BMI (-4.1%, p < 0.05), HbA(1c) (-1.4%, p < 0.05), FPG (-10.7%, p < 0.05), PPG (-16.2%, p < 0.05), FPI (-16.1%, p < 0.05), PPI (-26.9%, p < 0.05), HOMA index (-30.1%, p < 0.05), when compared to the baseline values. All these changes were reversed during the cross-over study phase, except those relating to HbA(1c), FPG and PPG. The only changes that significantly differed when directly comparing acarbose- and repaglinide-treated patients were those relating to FPI (-16.1% vs. +22.5%, respectively, p < 0.05) and HOMA index (-30.1% vs. +2.7%, p < 0.05). Conclusion: In addition from having a similar effect to repaglinide on PPG, acarbose appeared to have a more comprehensive positive effect on glucose metabolism compared to repaglinide in this relatively small sample of type 2 diabetic patients when used as add-on therapy to sulphonylureas and metformin.