Pharmacovigilance‐pharmacological investigations on sulfonylureas and glinides‐induced atrophy in skeletal muscle (1142.5)

Abstract

The atrophy of the skeletal muscle apparatus is a comorbidity condition in the diabetes type II representing a negative prognostic factor. The effects of the anti‐diabetic drugs on the diabetes type II‐related atrophy have never been investigated. The “in vitro” effects of the sulfonylureas (tolbutamide, glibenclamide and glimepiride) and glinides (repaglinide and nateglinide), well known KATP channel blockers, were evaluated on the protein content/muscle weight, fibers viability, mitochondrial SDH activity and channel currents in oxidative soleus(SOL), glycolitic/oxidative flexor digitorum brevis(FDB) and glycolitic extensor digitorum longus(EDL) muscle fibers of mice using biochemical and cell‐counting Kit‐8 assay, imagine analysis and patch‐clamp techniques. FDA‐adverse effects reporting system evaluation of atrophy‐related signals associated with the use of these drugs in humans has been performed. In animal experiments, all drugs after 24 h of incubation time reduced the protein content and fibers viability blocking the KATP channel and enhancing the SDH activity. Repaglinide and glibenclamide were the most potent drugs. In an eight month period, muscle atrophy was found in 0.27% of the glibenclamide reports in humans and in 0.022% of the other not sulfonylureas/glinides drugs. Glibenclamide induces atrophy in animals and in humans. Glimepiride shows a less potential of inducing atrophy.Grant Funding Source: none