Acarbose and metabolic control in patients with type 2 diabetes with newly initiated insulin therapy.

AIM: This study was designed to investigate the effect of acarbose in patients with type 2 diabetes with newly initiated insulin treatment who had previously been insufficiently controlled with oral antihyperglycaemic agents [haemoglobin A(1c) (HbA(1c)) >/= 8%]. METHODS: In this 20-week double-blind, placebo-controlled study, 163 patients were randomized to receive acarbose up to 100 mg three times a day or matching placebo. Both the groups were newly initiated with insulin, which was adjusted according to blood glucose values. Primary efficacy parameter was the change in HbA(1c) from baseline; changes in daily insulin doses were also assessed. RESULTS: Mean HbA(1c) was significantly reduced by acarbose compared with placebo (2.31 vs. 1.81%, p = 0.033). Insulin doses were comparable at the end of the study. There was no difference in blood glucose and triglyceride levels between the treatment groups. Postprandial serum insulin levels increased in both treatment arms owing to insulin administration but less so under acarbose. In contrast to the placebo group, an increase in body mass index was prevented for acarbose-treated patients. CONCLUSION: As adjunct administration to newly initiated insulin therapy, acarbose enhances the optimization of blood glucose control in patients with type 2 diabetes.

Safety and efficacy of acarbose in the treatment of Type 2 diabetes: data from a 5-year surveillance study.

This 5-year surveillance study assessed the tolerability and safety of acarbose in patients with diabetes. A total of 2035 patients were enrolled of whom 1954 were classified as having Type 2 diabetes. The study was open with no control group. Physicians had sole control of the acarbose doses prescribed. Fasting blood glucose levels, 2-h postprandial glucose levels, HbA(1) or HbA(1c) and other clinical parameters, such as lipids and liver enzyme levels, were also assessed as measures of efficacy and safety. One-third of the patients received acarbose as monotherapy and two-thirds in combination with other glucose-lowering treatment. The concomitant diseases were also assessed. Doses of acarbose were low in the majority of the patients and well tolerated. The incidence of acarbose-associated side effects was 4.7%. No sustained adverse changes in laboratory measures occurred. Over the 5 years, HbA(1) and glycated haemoglobin (HbA(1c)) decreased by 2.4 and 1.8% points, respectively, and the mean fasting glucose and 2-h postprandial glucose decreased by 2.7 and 3.4 mmol/l. Mean body weight was reduced by 0.9 kg. The results suggest that when used in long-term day-to-day management of diabetes, acarbose is well tolerated and can improve glycaemic control as monotherapy, as well as in combination therapy. In a high-risk patient group acarbose proved to be a safe drug.

Effects of acarbose treatment in Type 2 diabetic patients under dietary training: a multicentre, double-blind, placebo-controlled, 2-year study.

This 24-months, placebo-controlled, double-blind, randomised, group comparison study investigated the effect of acarbose vs placebo for improving metabolic control in patients with Type 2 diabetes under dietary training insufficiently controlled by diet alone. Patients randomised to acarbose had their dose increased in a stepwise manner to week 5. From week 5 onwards, they received 100 mg three times daily. This incremental dosing scheme was matched in the placebo group. All patients received specialist, intensive, continuous dietary training and counselling throughout the 2 yr of the study. Of the 74 patients randomised, 60 were included in the per-protocol analysis (28 receiving acarbose; 32 receiving placebo). HbA1c was the primary target variable. Per-protocol analysis found that, after 24 months, the mean difference in HbA1c relative to baseline value was -1.71+/-1.6% in the acarbose group and -0.82+/-1.1% in the placebo group. End-point values were 6.85+/-1.7% in the acarbose group and 7.41+/-1.1% in the placebo group. This difference between acarbose and placebo was statistically significant (p=0.02). Patients were defined as responders if they did not require additional treatment with an antidiabetic agent during the study. The responder rate under acarbose therapy was 89%, compared with 47% for placebo (p=0.0005). Acarbose-treated responders improved their HbA1c level to 6.45+/-0.82% after 24 months. The efficacy of acarbose was consistent throughout the study; decreasing efficacy was not evident. The results demonstrate the efficacy of acarbose for improving metabolic control in patients with Type 2 diabetes, even when such patients receive good dietary treatment and counselling.

Efficacy and safety of acarbose in the treatment of type 2 diabetes: data from a 2-year surveillance study.

This 2-year surveillance study assessed the tolerability and safety of acarbose in patients with diabetes. A total of 2035 patients were enrolled; approximately 95% were classified as having Type 2 diabetes. The study was open with no control groups. Physicians had sole control of the acarbose doses prescribed. Doses of acarbose were generally low, and hence well-tolerated. The incidence of acarbose-associated adverse effects and withdrawals was 7.5 and 2.5%, respectively. No sustained adverse changes in laboratory parameters occurred. Fasting blood glucose levels, 1- and 2-h postprandial glucose levels, HbA1c or HbA1, and other clinical parameters, such as blood cell counts and liver enzyme levels were also assessed as measures of efficacy and safety. Over the 2 years the mean fasting blood glucose level decreased by 2.39 mmol/l in patients with Type 2 diabetes, while mean 1- and 2-h postprandial blood glucose levels both decreased by 3.56 mmol/l. HbA1 and HbA1c decreased by 2.0 and 1.1 percentage points, respectively. These results suggest that when used in long-term day-to-day management of diabetes, acarbose is well tolerated and can improve glycaemic control.

Genetic heterogeneity of severe von Willebrand disease type III in the German population.

The genetic heterogeneity of severe von Willebrand disease (vWd) type III was estimated by analysing extended haplotypes of eleven intragenic restriction fragment length polymorphisms and one variable number of tandem repeat polymorphism in 32 patients from 28 families from Germany or of German origin. All patients were screened for gross deletions and for mutations at potential "hot spot" regions of the von Willebrand factor (vWf) gene. Disease-associated haplotypes were established in 24 families. Only a few, apparently unrelated families shared common haplotypes suggesting a considerable genetic heterogeneity in the German population of vWd type III patients. Defects causing vWd type III were identified on 14 out of 56 chromosomes (25%). Gross deletions were detected in two families. A complete homozygous deletion of the vWf gene was displayed in one patient. Another patient was compound heterozygous for a large deletion of at least 100 kb of the vWf gene with an additional, as yet unidentified, defect. One homozygous missense mutation was detected in exon 10, and two nonsense mutations were detected in exon 8 and exon 45 of the vWf gene, respectively. A frameshift mutation (delta C) in exon 18 was identified in five families and an additional frameshift mutation (delta G) was found in exon 28 in one family. It appears that delta C is the most common molecular defect in German patients with vWd type III. Its association with a number of different haplotypes suggests repeated de novo mutations at a mutation "hot spot". Evidence is presented that particular molecular defects causing vWd type III are associated with different patterns of inheritance, depending on their location within the vWf gene. Complete deletions of the gene and nonsense mutations in the pro-sequence are correlated with recessive inheritance, whereas frameshift and nonsense mutations in the gene sequence corresponding to the mature vWf subunit tend to be inherited in a dominant fashion.