Long-term improvement of metabolic control by acarbose in type 2 diabetes patients poorly controlled with maximum sulfonylurea therapy.

BACKGROUND AND OBJECTIVE

Multiple oral therapies are required long term for the majority of patients with type 2 diabetes mellitus to achieve acceptable glycaemic levels; alternatively, insulin therapy has to be initiated. This study investigated the addition of acarbose to maximum doses of sulfonylurea in very poorly controlled type 2 diabetes patients and assessed its effect in delaying further glycaemic deterioration.

STUDY DESIGN

In this 78-week, double-blind, placebo-controlled European study, patients were randomised to receive acarbose, titrated to a maximum dose of 100mg three times daily, or matching placebo. Concomitant sulfonylurea treatment (glibenclamide/gliclazide) was to remain unchanged throughout the study. A sample size of 171 patients per treatment arm was calculated. The primary efficacy analysis was intention to treat.

METHODS

The change in glycosylated haemoglobin (HbA(1c)) levels from baseline to the end of the study was regarded as the primary efficacy variable. Patients whose HbA(1c) levels increased above 10.5% on two consecutive visits terminated the study prematurely because of insulin administration. Secondary efficacy variables included the changes in blood glucose and C-peptide, both at fasting and at the 1h-postprandial level.

PATIENTS

A total of 330 patients (acarbose 164, placebo 166) were valid for the efficacy analysis. Patients were generally overweight (body mass index 29.0 kg/m(2)) and showed very poor metabolic control (HbA(1c) >9%, fasting blood glucose >200 mg/dL, and 1h-postprandial blood glucose >300 mg/dL).

RESULTS

Acarbose significantly improved HbA(1c) levels compared with placebo (least square mean [LS-mean] difference -0.54%, 95% CI -0.86 to -0.22; p = 0.001). A number of patients had to discontinue the study prematurely because of insulin administration (24.5% in the placebo and 14.2% in the acarbose group). There was a significant LS-mean difference of -14.8 mg/dL (p = 0.0195) in fasting blood glucose levels and highly significant differences in 1h-postprandial blood glucose (LS-mean difference -33.4 mg/dL, p < 0.0001) and in the rise in blood glucose from fasting to 1h-postprandial (LS-mean difference -19.6 mg/dL, p = 0.0001), all in favour of acarbose. Acarbose was shown to have a good safety profile and was generally well tolerated.

CONCLUSION

Acarbose was shown to have the potential to delay further deterioration of glucose control in type 2 diabetes patients who are very poorly controlled with maximum sulfonylurea doses.