Drug-Drug Interactions of Metformin in Diabetes Treatment
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Abstract
Metformin is a blood sugar-lowering medication in the biguanide class. Its mechanism of action involves inhibiting glucose production in the liver, which suppresses gluconeogenesis and lipolysis. Additionally, it reduces the secretion of growth hormone, adrenocorticotropic hormone (ACTH) and follicle stimulating hormone (FSH) from the pituitary gland, thereby decreasing insulin resistance. The effectiveness of metformin in lowering HbA1c ranges from 1-2% from baseline. After absorption into the bloodstream, metformin is distributed throughout the body via OCT1 and OCT3 transporters. It does not undergo hepatic metabolism and is excreted unchanged through OCT1 and MATE1 transporters found in the liver and kidneys. Concomitant use of metformin with drugs that inhibit OCT and MATE transporters can increase metformin levels in the bloodstream. Such drugs include INSTI antiviral drugs, trimethoprim, cephalexin, rifampicin, pyrimethamine, H2 receptor inhibitors, proton pump inhibitors, ranolazine, anti-cancer drugs, and beta-adrenergic blockers. Additionally, the use of metformin with drugs that increase gastric emptying time, such as anticholinergics, may enhance metformin absorption in the small intestine. Furthermore, exposure to radiographic contrast agents that are nephrotoxic can lead to acute kidney failure, reducing metformin excretion and increasing the risk of lactic acidosis. Heavy alcohol consumption may also contribute to lactic acidosis. Therefore, patients taking metformin should avoid excessive alcohol intake to minimize the risk of this condition. Drug interactions that increase metformin levels may lead to severe adverse effects, including metformin-induced lactic acidosis (MILA) or metformin-associated lactic acidosis (MALA). Thus, drug interaction is a critical issue to be concerned together with comorbidities and concurrent medications. Patient counseling is essential to prevent severe adverse effects resulting from drug interactions.
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ผลการวิจัยและความคิดเห็นที่ปรากฏในบทความถือเป็นความคิดเห็นและอยู่ในความรับผิดชอบของผู้นิพนธ์ มิใช่ความเห็นหรือความรับผิดชอบของกองบรรณาธิการ หรือคณะเภสัชศาสตร์ มหาวิทยาลัยสงขลานครินทร์ ทั้งนี้ไม่รวมความผิดพลาดอันเกิดจากการพิมพ์ บทความที่ได้รับการเผยแพร่โดยวารสารเภสัชกรรมไทยถือเป็นสิทธิ์ของวารสารฯ
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