A tale about perfect partners: New horizons in glimepiride and metformin Mechanisms of action

Abstract

The sustainability of the effects, the improvement of directlydamaged and associated organ dysfunction, acceptable oraltolerability and lower side effects are probably the desiredoutcomes of any pharmacological therapy, especially for onethat is used for long periods of time, such as T2DM pharmacotherapy.Biguanides and Sulfonylureas have a commondevelopment history, both associated with the economic difficultiesassociated with both World Wars and the impactcaused by the discovery and application of Insulin for diabetesmanagement. Glimepiride, the third generation sulfonylurea,is a KTP channel modulator, which also happens to influenceplasma membrane dynamics, pro-inflammatory cytokine secretionand PPAR-π activation. The biological effects of metforminare widening every day, and they are not only relatedwith the activation of AMP-dependent Kinase, but also withmitochondrial bioenergetics, glycogen and monocarbon metabolisms,epigenetic silencing and cell death pathways. Theindividual effects of glimepiride added to metformin´s couldvery much improve the patient´s metabolic and cardiovascularprofiles, especially when such benefits are obtained withlower dosages than the standard. Such properties not onlycould guarantee adhesion to the oral medication but couldenhance the prognosis of T2DM patients. The purpose ofthe following review is to describe the effects of glimepirideand metformin from a biological standpoint, including theirrecently pleiotropic effects.