Influence of Acarbose on Blood Glucose and Breath Hydrogen after Carbohydrate Load with Sucrose or Starch

Abstract

A monocentric, open, randomised, single-dose, six-period crossover trial was carried out in healthy volunteers under fasting conditions to establish the most appropriate study design for a pivotal bioequivalence trial with acarbose (CAS 56180-94-0) regarding a) dosage of the drug, b) type of carbohydrate load, c) type of primary endpoint, and d) sample size. 50 g sucrose or 50 g starch were used as carbohydrate load. Acarbose was administered in doses of 50 and 200 mg. Blood glucose and breath hydrogen were evaluated as endpoints. Both acarbose doses reduced the effect of carbohydrate load. Blood glucose: no statistically significant difference could be noted between the overall effect of 50 mg and that of 200 mg acarbose irrespective of the type of carbohydrate load. Breath hydrogen: an influence could be shown only for sucrose as carbohydrate load. Practically no effect was observed with starch. The overall increase of effect is by more than 200% with sucrose when the dose of acarbose increases from 50 to 200 mg. This difference between the effects of both doses of acarbose on breath hydrogen is statistically significant. For a pivotal trial, sucrose is the most appropriate type of carbohydrate load, baseline adjusted area under the breath hydrogen response is the most appropriate primary endpoint, and a dose of 100 mg acarbose is the most appropriate dosage. A total number of 100 subjects will be needed for proving pharmacodynamic equivalence between two acarbose products in a pivotal trial.

SalaciaExtract Improves Postprandial Glucose and Insulin Response: A Randomized Double-Blind, Placebo Controlled, Crossover Study in Healthy Volunteers

“…So administration of sucrose was recommended to provide a better baseline measure of α -glucosidase activity. Koytchev et al [ 40 ] administration of sucrose is more suitable than eating a meal since it produces a more reproducible change in serum glucose concentration. Studies on low dose SCE were not reported in healthy people nor in disease condition.…”

Acarbose Bioequivalence: Exploration of New Pharmacodynamic Parameters

“…Thus, in the FDA guidelines for demonstrating acarbose BE published in 2009, administration of sucrose was recommended to provide a better baseline measure of α-glucosidase activity. As found by Koytchev et al (2009), administration of sucrose is more suitable than eating a meal since it produces a more reproducible change in serum glucose concentration (4).…”

Acarbose: safe and effective for lowering postprandial hyperglycaemia and improving cardiovascular outcomes

“…Additionally, it suggested increased incidence of gastrointestinal symptoms with sugar rich soft drink consumption. 168 Thus, rational use, slow titration from low to medium dose, focused patient education and good dietary advice may help ameliorate the gastrointestinal adverse effects associated with acarbose.…”