Combination Therapy «Metformin + Glimepiride» in Patients with Type 2 Diabetes Mellitus (Molecular Mechanisms for Optimization of the Rehabilitation Effect)

V.V. Poltorak, N.S. Krasova, M.Yu. Horshunskaia

Abstract


This review describes the molecular mechanisms of therapeutic action of the combination of oral antidiabetic drugs «metformin + glimepiride», aimed at the correction of both defects, which determine the development of metabolic abnormalities in type 2 diabetes mellitus, namely, relative insulin deficiency and insulin resistance. The combination of metformin with glimepiride is optimal in terms of therapeutic effects on both molecules, which metabolic hypoactivity determines the metabolic state of insulin resistance, respectively, adenosine monophosphate-activated protein kinase and peroxisome proliferator-activated receptor γ. In addition, metformin has unique ability to eliminate the phenomenon of «hyperglycemic memory» by increasing the expression and activity of sirtuin-1. On the other hand, the third generation sulfonylurea glimepiride provides a «gentle» stimulation of the β-cells, which maintains the physiological ratio proinsulin/insulin and slows down the development of the phenomenon of β-cell desensitization to physiological and pharmacological stimuli. Glimepiride retains protective phenomenon of ischemic preconditioning and extends the range of therapeutic effect on the pathophysiological components of insulin resistance due to insulin-mimetic and insulin-sensitizing effect, as well as potentiates the beneficial effects of metformin (particularly, via adiponectin). Above mentioned determinated the achievement of optimized therapeutic efficacy of pharmaceutical combination against the background of decreased side effects (reduced dose of glimepiride, metformin).


Keywords


type 2 diabetes mellitus; metformin; glimepiride

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DOI: https://doi.org/10.22141/2224-0721.1.65.2015.75906

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