The Glucoregulatory Mechanisms, Pharmacokinetics and Pharmacogenetics of Metformin in Type 2 Diabetes Mellitus | ||||
| Journal of Advanced Pharmacy Research | ||||
| Article 6, Volume 8, Issue 2, April 2024, Page 93-106 PDF (397.97 K) | ||||
| Document Type: Review Article | ||||
| DOI: 10.21608/aprh.2024.273831.1257 | ||||
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| Authors | ||||
Haila NAESA   ; Dima JOUJEH
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| Biotechnology engineering, Faculty of Technical engineering, University of Aleppo, Syria | ||||
| Abstract | ||||
| Background and Objective: Type 2 diabetes (T2D) is a common chronic disease affecting more than 420 million people worldwide. Metformin, a biguanide drug that lowers blood glucose remains the first-choice drug for T2D. In this review, we mainly discusse the available data on the mechanism of action, pharmacokinetics and pharmacogenetics of metformin and review the evidence for an association between genetic variation and metformin response in T2D patients. Methods: This review was created by searching Pubmed and Google Scholar, using the following keywords to find research published in English in PubMed, and google scholar: “Type 2 diabetes”, “metformin”, “pharmacokinetics”, “pharmacogenetics”, “precision medicine”, “genetic variation”, “mechanism of action”, “drug response”. Key Content and Findings: Several mechanisms have been proposed to explain the metformin action in T2D patients, including activation of AMPK, suppression of hepatic glucose production, inhibition of mitochondrial complex 1, stimulation of insulin-stimulated glucose uptake into skeletal muscle, reducing the intestinal glucose absorption, modulation of the gut microbiota and increasing insulin sensitivity. However, metformin does not work the same way for everyone. It is well established that interindividual differences in the human genome influence individual responses to the same drug therapy. Pharmacogenetic studies mainly focused on single nucleotide polymorphism based variations and demonstrated that there is association between several SNPs in metformin pharmacokinetic genes and some pharmacodynamic genes, and metformin responsiveness in T2D. Conclusions: Although great progress has been made in understanding the pharmacogenetics of metformin response,there are still significant gaps in that need to be filled before implementation in clinical practice. Therefore, further research is needed. We hope that this review will help facilitate more effective use of the drug to treat T2D. | ||||
| Keywords | ||||
| Type 2 diabetes; Metformin; Pharmacokinetics; Pharmacogenetics; Genetic variation | ||||
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