Imeglimin Hydrochloride

Imeglimin Hydrochloride works in two ways. (a) It amplifies glucose-stimulated insulin secretion (GSIS) and preserves β-cell mass. (b) It enhances insulin action, which includes the potential to inhibit hepatic glucose output and to improve insulin signalling in both liver and skeletal muscle. At the cellular and molecular level, Imeglimin may act by correcting mitochondrial dysfunction, a common underlying element of T2D pathogenesis. It has been observed to rebalance respiratory chain activity, with partial inhibition of Complex I and correction of deficient Complex III activity. This reduces reactive oxygen species formation (so oxidative stress falls) and prevents opening of the mitochondrial permeability transition pore, which is implicated in preventing cell death. In islets taken from diseased rodents with T2D, Imeglimin also enhances glucose-stimulated ATP generation and induces the synthesis of nicotinamide adenine dinucleotide (NAD+) through the 'salvage pathway'. NAD+ is a key mitochondrial co-factor, and its metabolites may also contribute to the increase in GSIS (via enhanced Ca++ mobilization). Imeglimin has also been shown to preserve β-cell mass in rodents with T2D. So it appears to target a key root cause of T2D, which is defective cellular energy metabolism. This potential mode of action is unique and has been shown to differ from that of other major therapeutic classes, including biguanides, sulphonylureas and glucagon-like peptide-1 receptor agonists.