Comparison of acarbose and metformin in patients with Type 2 diabetes mellitus insufficiently controlled with diet and sulphonylureas: a randomized, placebo-controlled study.

AIMS: To compare the efficacy and safety of acarbose and metformin when added to sulphonylurea therapy in diabetic patients insufficiently controlled with sulphonylureas alone. METHODS: A 12-week, single-centre, placebo-controlled study, with 89 patients randomized to receive acarbose (100 mg t.d.s.), metformin (850 mg b.d.) or placebo in addition to their sulphonylurea therapy. The study was double-blinded with respect to acarbose/placebo and single-blinded for metformin/ acarbose and metformin/placebo. Patients started a strict dietary regimen 1 week before receiving their first dose of acarbose, metformin or placebo. This regimen was individually adjusted to metabolic status and energy requirements. RESULTS: The primary endpoint, HbA1c, decreased from baseline in all three groups after 12 weeks. The decrease was greater in the two groups receiving active therapy compared with placebo (acarbose -2.3+/-0.32%; metformin -2.5+/-0.16%; placebo -1.3+/-0.34%). There was no significant difference between acarbose and metformin (P=0.65). Differences between both active therapies and placebo were statistically significant (acarbose P < or = 0.01; metformin P < or = 0.004). Reductions in body weight over the treatment period were seen in all three groups and were greatest in the acarbose group (median weight reduction: acarbose 3.5 kg; metformin, 1.0 kg; placebo 1.4 kg). There were no significant differences in the incidence of gastrointestinal side-effects between the three groups and all regimens were generally well tolerated. CONCLUSION: The results of the study demonstrate the equivalence of acarbose and metformin for improving metabolic control in patients insufficiently controlled with diet and sulphonylureas.

Glucagon-like peptide 1 and its potential in the treatment of non-insulin-dependent diabetes mellitus.

Studies examining small groups of type 2-(NIDDM) diabetic patients have shown the potential of glucagon-like peptide 1 (GLP-1) to normalize fasting hyperglycaemia. Patient characteristics determining the size of the effect have not been reported. Therefore, the results of four studies were analysed. Exogenous GLP-1 was administered i.v. or s.c. in 37 type 2-diabetic patients, age 60 +/- 8 years; BMI 28.2 +/- 5.3 kg/m2; HbA1c 10.6 +/- 1.6%; diabetes duration 10 +/- 6 years, treatment with sulfonylureas, n = 33, metformin, n = 11, acarbose, n = 3. Results were analysed using repeated measures analysis of variance and multiple regression analysis. Exogenous GLP-1 lowered fasting plasma glucose within 4-5 h from 12.8 +/- 2.5 to 5.3 +/- 1.3 mmol/l (placebo: 12.8 +/- 2.3 to 10.0 +/- 2.2; p < 0.0001 for the interaction of treatment and time). Only fasting glycaemia (p = 0.0085) and the route (i.v. vs. s.c.; p = 0.05), but not gender, age, BMI, HbA1c, diabetes duration, treatment with sulfonylureas, metformin or acarbose, were significant predictors of the plasma glucose concentrations reached after the administration of GLP-1 (variation: 3.4-8.5 mmol/l). In conclusion, GLP-1 is able to normalize plasma glucose in all type 2-diabetic patients studied. This analysis underlines the great therapeutic potential of GLP-1.

[Effectiveness and tolerance of long-term acarbose therapy in diabetic patients with threatened secondary failure of sulfonylurea drug treatment]. / Wirksamkeit und Verträglichkeit einer längerfristigen Acarbosetherapie bei Diabetikern mit drohendem Sekundärversagen einer Sulfonylharnstoffbehandlung.

The efficacy and tolerability of acarbose was studied in 14 type-2-diabetic patients poorly controlled with diet and sulfonylureas. Acarbose was given in addition to sulfonylureas in a single-blind, placebo-controlled study for three times three months (acarbose-placebo-acarbose). At the beginning of the study and every three months body weight, HbA1c and biochemical and hematological safety parameters were measured. The patients controlled their mid morning urine glucose and two to four times daily their blood glucose concentration with a memory glucometer. Diabetic control improved significantly: HbA1c was 8.5 +/- 1.4% at the beginning, 6.5 +/- 1.1% after three months with acarbose (p < 0.001), 7.2 +/- 0.9% after three months placebo (p < 0.01) and 6.7 +/- 1.3% again after three months with acarbose (p < 0.05). Thus, the effect of acarbose alone accounts for 0.7 or 0.5% respectively, whereas the effect of teaching and diet in a special diabetes unit (the difference from the study to placebo) accounts for 1.3% of HbA1c. Home monitored blood and urine glucose values were improved: The postprandial blood glucose concentrations, the postprandial differences, the mean blood glucose concentrations and the glycosuria were decreased during acarbose treatment in comparison with placebo. The preprandial blood glucose concentrations before breakfast and supper were not influenced by acarbose. Hematological and biochemical safety parameters as well as blood pressure and heart rate were unchanged. Meteorism and flatulence as typical side effects decreased during treatment. Acarbose is a safe and effective adjunct treatment for type-2-diabetic patients uncontrolled with diet and sulfonylurea alone.

[Delayed absorption of carbohydrates in the therapy of Type II diabetes: comparison between dietary (Muesli) and pharmacological (Alpha-glucosidase inhibition) modification]. / Resorptionsverzögerung der Kohlenhydrate in der Therapie des Typ-II-Diabetes: Vergleich zwischen diätetischer (Müsli) und pharmakologischer (alpha-Glucosidasehemmung) Beeinflussung.

Slowly resorbable carbohydrates are preferred in the dietetic therapy of patients with type 2 diabetes. In this study we compared the efficacy of a "müsli" with the alpha-glucosidase inhibitor miglitol in delaying the resorption of carbohydrates. 24 patients with NIDDM took, in randomized order, four different breakfasts with equal amounts of carbohydrate: a standard breakfast with bread and marmelade, a müsli, and both breakfasts with 100 mg miglitol. We calculated the maximal blood glucose concentration, the postprandial difference, the time of the maximum and the area under the curve (AUC). The postprandial blood glucose increase after the müsli breakfast was significantly lower compared with the standard breakfast (maximal blood glucose 12.3 vs. 13.9 mmol/l, postprandial difference 3.6 vs. 5.1 mml/l, AUC 360 vs, 468 mmol/l x min). The blood glucose increase after the standard breakfast with miglitol was even lower (maximum 11.6 mmol/l, postprandial difference 2.9 mmol/l, AUC 241 mmol/l x min). Miglitol also lowered the blood glucose values after the müsli breakfast. This study shows that the alpha-glucosidase inhibitor miglitol in a dose of 100 mg is more effective in lowering the postprandial blood glucose increase than a müsli. In cases of non-acceptance of a modern diet with slowly resorbable carbohydrates, alpha-glucosidase inhibitors may be a therapeutic alternative.

Smoothing effect of a new alpha-glucosidase inhibitor BAY m 1099 on blood glucose profiles of sulfonylurea-treated type II diabetic patients.

The alpha-glucosidase inhibitor BAY m 1099, a deoxynojirimycin derivative, was studied in sulfonylurea-treated type II diabetic patients using a placebo-controlled double-blind cross-over design. Given in two daily doses the inhibitor smoothened the blood glucose profile by lowering significantly post-prandial blood glucose peaks. Fasting and daily mean blood glucose levels measured as the area under the blood glucose curves were however not influenced significantly. This might be due to the short duration of the treatment periods or the low dosage of the drug. Abdominal side effects were negligible. The alpha-glucosidase inhibitor BAY m 1099 might become a useful therapeutic tool in addition to sulfonylurea treatment in type II diabetes.