Acarbose in Treating Type 1 & Type 2 Diabetes Mellitus
Objective: To assess the safety profile of acarbose treatment over a 1-year period at a dose range of 50300mg three times daily in patients with type 1 or type 2 diabetes mellitus.
Study Design and Patients: In this 56-week, double-blind, parallel-group, multicentre comparison, patients were randomised to acarbose or placebo in a 2:1 ratio. An 8-week forced titration phase (from 50300mg three times daily) was followed by a 48-week maintenance phase during which patients received the highest dose tolerated during titration. Patients were assessed at 13 visits with respect to adverse events/intercurrent illnesses, abnormal laboratory values (serum chemistry, urinalysis, complete blood and reticulocyte count, serum iron and total iron binding capacity, and serum vitamin B6, B12, D and folate levels), discontinuation rates, ECG findings, vital signs and evaluation of the patients' diaries with regard to gastrointestinal events. A total of 359 patients (acarbose 240, placebo 119) were valid for analysis; 21% had type 1 diabetes. Most patients received concomitant insulin or sulfonylurea treatment.
Results: Study withdrawal was reported for 35% of acarbose and 24% of placebo recipients (p = 0.053); adverse events were the main reason for withdrawal in acarbose recipients (20%; placebo group 5%; p < 0.01). The most common adverse events for acarbose recipients were gastrointestinal (abdominal pain, flatulence and diarrhoea), which were more frequent than in placebo patients (p < 0.01). These events occurred more often early in the study and attenuated over time.
Conclusion: Acarbose was safe and well tolerated by the majority of diabetic patients over a 1-year treatment period.
The κ-glucosidase inhibitor acarbose is one of several treatment options for diabetes mellitus. It binds reversibly and competitively to the oligosaccharide binding site of κ-glucosidase enzymes in the brush border of the small intestinal mucosa, and thus delays the enzymatic breakdown of carbohydrates. As a consequence, postprandial glucose absorption occurs at a reduced rate. The mechanism of action of acarbose Results in reduction in postprandial hyperglycaemia and hyperinsulinaemia in patients with type 2 diabetes and reduction in postprandial blood glucose peaks and a decrease in insulin requirement in type 1 diabetics. Numerous clinical studies have demonstrated the efficacy of acarbose as first-line or adjunct treatment in type 2 diabetics and a beneficial effect in addition to insulin in type 1 diabetic patients. Acarbose has been shown to delay progression to type 2 diabetes in subjects with impaired glucose tolerance (IGT), and can reduce the risk of developing cardiovascular events (in particular myocardial infarction) in IGT subjects and type 2 diabetics. Long-term efficacy has also been proven.
Because most patients with diabetes require long- term treatment, the safety and tolerability profile of the administered antidiabetic treatment is of great importance. Acarbose can be associated with gastrointestinal adverse effects; in previous phase III studies in the US, anaemia and liver enzyme abnormalities were also occasionally reported. Gastrointestinal adverse effects are directly related to the mechanism of action of acarbose and are caused by the fermentation of unabsorbed carbohydrates in the large bowel. The objective of this study was to further investigate the safety and tolerability of acarbose treatment over a 1-year period at a dose range of 50300mg three times daily in patients with type 1 or type 2 diabetes, and to perform a thorough evaluation of the gastrointestinal adverse events profile.
Cardiovascular data for the type 2 diabetes study population in the current study have already been included in a recent meta-analysis showing the beneficial preventive effect of acarbose on myocardial infarction and any cardiovascular events.
Objective: To assess the safety profile of acarbose treatment over a 1-year period at a dose range of 50300mg three times daily in patients with type 1 or type 2 diabetes mellitus.
Study Design and Patients: In this 56-week, double-blind, parallel-group, multicentre comparison, patients were randomised to acarbose or placebo in a 2:1 ratio. An 8-week forced titration phase (from 50300mg three times daily) was followed by a 48-week maintenance phase during which patients received the highest dose tolerated during titration. Patients were assessed at 13 visits with respect to adverse events/intercurrent illnesses, abnormal laboratory values (serum chemistry, urinalysis, complete blood and reticulocyte count, serum iron and total iron binding capacity, and serum vitamin B6, B12, D and folate levels), discontinuation rates, ECG findings, vital signs and evaluation of the patients' diaries with regard to gastrointestinal events. A total of 359 patients (acarbose 240, placebo 119) were valid for analysis; 21% had type 1 diabetes. Most patients received concomitant insulin or sulfonylurea treatment.
Results: Study withdrawal was reported for 35% of acarbose and 24% of placebo recipients (p = 0.053); adverse events were the main reason for withdrawal in acarbose recipients (20%; placebo group 5%; p < 0.01). The most common adverse events for acarbose recipients were gastrointestinal (abdominal pain, flatulence and diarrhoea), which were more frequent than in placebo patients (p < 0.01). These events occurred more often early in the study and attenuated over time.
Conclusion: Acarbose was safe and well tolerated by the majority of diabetic patients over a 1-year treatment period.
The κ-glucosidase inhibitor acarbose is one of several treatment options for diabetes mellitus. It binds reversibly and competitively to the oligosaccharide binding site of κ-glucosidase enzymes in the brush border of the small intestinal mucosa, and thus delays the enzymatic breakdown of carbohydrates. As a consequence, postprandial glucose absorption occurs at a reduced rate. The mechanism of action of acarbose Results in reduction in postprandial hyperglycaemia and hyperinsulinaemia in patients with type 2 diabetes and reduction in postprandial blood glucose peaks and a decrease in insulin requirement in type 1 diabetics. Numerous clinical studies have demonstrated the efficacy of acarbose as first-line or adjunct treatment in type 2 diabetics and a beneficial effect in addition to insulin in type 1 diabetic patients. Acarbose has been shown to delay progression to type 2 diabetes in subjects with impaired glucose tolerance (IGT), and can reduce the risk of developing cardiovascular events (in particular myocardial infarction) in IGT subjects and type 2 diabetics. Long-term efficacy has also been proven.
Because most patients with diabetes require long- term treatment, the safety and tolerability profile of the administered antidiabetic treatment is of great importance. Acarbose can be associated with gastrointestinal adverse effects; in previous phase III studies in the US, anaemia and liver enzyme abnormalities were also occasionally reported. Gastrointestinal adverse effects are directly related to the mechanism of action of acarbose and are caused by the fermentation of unabsorbed carbohydrates in the large bowel. The objective of this study was to further investigate the safety and tolerability of acarbose treatment over a 1-year period at a dose range of 50300mg three times daily in patients with type 1 or type 2 diabetes, and to perform a thorough evaluation of the gastrointestinal adverse events profile.
Cardiovascular data for the type 2 diabetes study population in the current study have already been included in a recent meta-analysis showing the beneficial preventive effect of acarbose on myocardial infarction and any cardiovascular events.
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