Long-Term Improvement of Metabolic Control by Acarbose
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 (HbA1c) levels from baseline to the end of the study was regarded as the primary efficacy variable. Patients whose HbA1c 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) and showed very poor metabolic control (HbA1c >9%, fasting blood glucose >200 mg/dL, and 1h-postprandial blood glucose >300 mg/dL).
Results: Acarbose significantly improved HbA1c 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.
The United Kingdom Prospective Diabetes Study (UKPDS) has demonstrated that intensive glycaemic control is essential for risk reduction of diabetes-related complications. When dietary measures fail, oral antihyperglycaemic agents are the first treatment choice. In Germany, 53% of patients with type 2 diabetes mellitus are treated with oral antihyperglycaemic medication; approximately 58% of these patients receive sulfonylureas. Sulfonylurea therapy - like other antihyperglycaemic monotherapies - can, however, not prevent metabolic decline in the long term. Individual therapies are required to achieve acceptable glycaemic control, including insulin therapy in addition to oral antihyperglycaemic therapy. Insulin, however, is associated with a risk of hypoglycaemia and weight gain and many patients seek to avoid or postpone this treatment. A possible alternative is the addition of another oral antihyperglycaemic agent with a different mechanism of action such as acarbose. Whereas sulfonylureas increase serum insulin supply, the a-glucosidase inhibitor acarbose reduces and delays the digestion of complex carbohydrates and sucrose. The delayed absorption of glucose in turn reduces postprandial increases in blood glucose leading subsequently to reduced serum insulin values and overall improvement of glycaemic control. This was demonstrated in numerous clinical studies in type 1 and type 2 diabetes patients, either using monotherapy or a combination with other antihyperglycaemic medication.
This study investigated the effect of acarbose on delaying further deterioration of glycaemic control in type 2 diabetes patients very poorly controlled with maximum sulfonylurea doses.
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 (HbA1c) levels from baseline to the end of the study was regarded as the primary efficacy variable. Patients whose HbA1c 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) and showed very poor metabolic control (HbA1c >9%, fasting blood glucose >200 mg/dL, and 1h-postprandial blood glucose >300 mg/dL).
Results: Acarbose significantly improved HbA1c 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.
The United Kingdom Prospective Diabetes Study (UKPDS) has demonstrated that intensive glycaemic control is essential for risk reduction of diabetes-related complications. When dietary measures fail, oral antihyperglycaemic agents are the first treatment choice. In Germany, 53% of patients with type 2 diabetes mellitus are treated with oral antihyperglycaemic medication; approximately 58% of these patients receive sulfonylureas. Sulfonylurea therapy - like other antihyperglycaemic monotherapies - can, however, not prevent metabolic decline in the long term. Individual therapies are required to achieve acceptable glycaemic control, including insulin therapy in addition to oral antihyperglycaemic therapy. Insulin, however, is associated with a risk of hypoglycaemia and weight gain and many patients seek to avoid or postpone this treatment. A possible alternative is the addition of another oral antihyperglycaemic agent with a different mechanism of action such as acarbose. Whereas sulfonylureas increase serum insulin supply, the a-glucosidase inhibitor acarbose reduces and delays the digestion of complex carbohydrates and sucrose. The delayed absorption of glucose in turn reduces postprandial increases in blood glucose leading subsequently to reduced serum insulin values and overall improvement of glycaemic control. This was demonstrated in numerous clinical studies in type 1 and type 2 diabetes patients, either using monotherapy or a combination with other antihyperglycaemic medication.
This study investigated the effect of acarbose on delaying further deterioration of glycaemic control in type 2 diabetes patients very poorly controlled with maximum sulfonylurea doses.