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

Abstract:

The sustainability of the effects, the improvement of directly damaged and associated organ dysfunction, acceptable oral tolerability and lower side effects are probably the desired outcomes of any pharmacological therapy, especially for one that is used for long periods of time, such as T2DM pharmacotherapy. Biguanides and Sulfonylureas have a common development history, both associated with the economic difficulties associated with both World Wars and the impact caused by the discovery and application of Insulin for diabetes management. Glimepiride, the third generation sulfonylurea, is a KTP channel modulator, which also happens to influence plasma membrane dynamics, pro-inflammatory cytokine se-cretion and PPAR-π activation. The biological effects of metformin are widening every day, and they are not only related with the activation of AMP-dependent Kinase, but also with mitochondrial bioenergetics, glycogen and monocarbon metabolisms, epigenetic silencing and cell death pathways. The individual effects of glimepiride added to metformin’s could very much improve the patient’s metabolic and cardiovascular profiles, especially when such benefits are obtained with lower dosages than the standard. Such properties not only could guarantee adhesion to the oral medication but could enhance the prognosis of T2DM patients. The purpose of the following review is to describe the effects of glimepiride and metformin from a biological standpoint, including their recently pleiotropic effects.