Miglitol

Miglitol is a reversible inhibitor of intestinal alpha-glucosidases. Under the influence of miglitol, the digestion of complex carbohydrates into absorbable monosaccharides in the small intestine is dosedependently delayed. Administration of miglitol thus leads to reduced postprandial hyperglycaemia and a smoothing effect on fluctuations in the daily blood glucose profile. The absorption of orally administered glucose is not inhibited by miglitol.

In contrast to sulfonylureas miglitol does not stimulate pancreatic insulin secretion.

Treatment with miglitol also results in a reduction of fasting blood glucose and to changes in levels of glycosylated haemoglobin (HbA₁, HbA_1c). The changes may be a reduction or reduced deterioration in HbA₁ or HbA_1c levels, depending upon the patient’s clinical status and disease progression. These parameters are affected in a dose-dependent manner by miglitol.

The pharmacodynamic action of miglitol is local in the gastro-intestinal tract.

Following oral administration of low doses of miglitol (12.5 to 25mg), the compound is almost quantitatively absorbed. Increasing the oral dose of miglitol from 25 to 200 mg resulted in non-linear changes in its absorption. Within the recommended dosage range, approximately 90% of a 50 mg dose is absorbed in comparison to 60% of a 100 mg dose. The absorption characteristics of miglitol follow Michaelis-Menten kinetics with an absorption window of 6-10 hours following administration. Its steady-state volume of distribution (V_ss) of 0.18 l/kg indicates that miglitol is distributed principally in the extracellular space. Miglitol is bound to plasma proteins only in negligible quantities (<4%).

The drug is not metabolised in the gut or after absorption, but is eliminated unchanged almost exclusively via the kidneys. Miglitol clearance may be reduced in patients with impaired renal function. The biliary excretion of miglitol is negligible (<1%). The total body clearance is therefore equal to the renal clearance (99 to 114 ml/min in young non-patient volunteers), and corresponds to the glomerular filtration rate. The apparent terminal half-life, t_1/2, in the majority of young non-patient volunteers is in the range of 2-3 hours.

In chronic toxicity studies weight loss was the dose-limiting toxicity. Specific target organs for toxicity could not be determined.

Miglitol had no genotoxic potential in a battery of genotoxicity tests, and there was no sign of miglitolinduced carcinogenicity in mice and rats.