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Article History:
Received: 2 August 2017
Revised: 12 September 2017
Accepted: 13 September 2017
ePublished: 31 December 2017
Keywords:
* Metformin
* Drug interactions
* rganic Cation Transporters
* Multidrug and Toxin Extruders
* Pharmacokinetic interactions
Abstract
Metformin is a most widely used medication all around the world to treat Type 2 diabetes mellitus. It is also found to be effective against various conditions including, Prediabetes, Gestational diabetes mellitus (GDM), Polycystic Ovarian Syndrome (PCOS), Obesity, Cancer, etc. It is a cationic drug and it depends Organic Cation Transporters (OCTs) and Multidrug and Toxin Extruders (MATEs) mostly for its pharmacokinetics movement. The probability of drug interaction increases with the number of concomitant medications. This article focuses the drug interactions of metformin and most of them are linked to the inhibition of OCTs and MATEs leading to increased plasma metformin concentrations and subsequent elevation of risk of Metformin Associated Lactic Acidosis (MALA). By identifying the drugs inhibiting OCTs and MATEs, the healthcare professionals can predict the drug interactions of metformin.
Introduction
Metformin is a popular drug and is used by millions worldwide to treat various conditions including Type 2 diabetes mellitus, Prediabetes, Gestational diabetes mellitus (GDM), Polycystic Ovarian Syndrome (PCOS), Obesity, Cancer, etc.
Metformin is primarily used as a first line drug for the treatment of type 2 diabetes mellitus in overweight patients.1-3 It is postulated that the antihyperglycemic action of Metformin results from decreased hepatic glucose production largely by inhibiting gluconeogenesis4,5 and increased glucose utilization.6 The activation of AMP-activated protein kinase (AMPK) by Metformin is required for the inhibition of hepatic glucose production and induction of skeletal muscle glucose uptake.7
Pharmacokinetic drug interactions of Metformin
Metformin is a cation at physiological pH, as it is a strong base. Hence, the absorption, distribution and excretion of Metformin depend on the transporters such as Organic Cation Transporters (OCTs), Multidrug and Toxin Extruders (MATEs) and Plasma membrane Monoamine Transporter (PMAT).8 The oral absorption and hepatic uptake of Metformin are mediated possibly by Organic cation transporters (OCTs) (OCT1 and OCT3) and renal excretion of Metformin is largely mediated by Metformin transporters such as Multidrug and Toxin Extruders (MATEs) MATE1 and MATE2-k and Organic cation transporter 2 (OCT2).9 Metformin is not metabolized and excreted unchanged in urine10 and...