Metformin is the most often prescribed drug for people with type 2 diabetes (T2D). More than 120 million patients with T2D use metformin worldwide. However, monotherapy fails to achieve glycemic control in a third of the treated patients. Genetics contribute to some of the inter-individual variations in glycemic response to metformin. Numerous pharmacogenetic studies have demonstrated that variations in genes related to pharmacokinetics and pharmacodynamics of metformin's encoding transporters are mainly associated with metformin response. The goal of this review is to evaluate the current state of metformin pharmacogenetics and metabolomics research, discuss the clinical and scientific issues that need to be resolved in order to increase our knowledge of patient response variability to metformin, and how to improve patient outcomes. Metformin's hydrophilic nature and absorption as well as its action mechanism and effectiveness on T2D initiation are discussed. The impacts of variations associated with various genes are analysed to identify and evaluate the effect of genetic polymorphisms on the therapeutic activity of metformin. The metabolic pattern of T2D and metformin is also indicated. This is to emphasise that studies of pharmacogenetics and metabolomics could expand our knowledge of metformin response in T2D.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9812811 | PMC |
| http://dx.doi.org/10.7150/ijms.77206 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Allele frequency of genetic variations related to the gene-drug pair in a group of Iranian population.
J Diabetes Metab Disord
December 2024
Personalized Medicine Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
Objectives: The efficacy and safety of drug treatments vary widely due to genetic variations. Pharmacogenomics investigates the impact of genetic variations on patient drug response. This research investigates the frequency of genetic variations in the Iranian population, comparing them with global data to provide insights into the pharmacogenomic approach in the Iranian population.
View Article and Find Full Text PDFInhibition of heme-thiolate monooxygenase CYP1B1 prevents hepatic stellate cell activation and liver fibrosis by accumulating trehalose.
Sci Transl Med
September 2024
Center for Pharmacogenetics and Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, PA 15261, USA.
Article Synopsis
- Hepatic stellate cells (HSCs) play a crucial role in the development of liver fibrosis, and the enzyme CYP1B1 is found to be elevated in fibrotic liver tissue in both humans and mice.
- Targeted inhibition or removal of CYP1B1 in mice reduced HSC activation and provided protection against liver fibrosis caused by various damaging substances, particularly in male mice.
- The study highlights trehalose, a disaccharide that increases in CYP1B1-deficient HSCs, as a potential antifibrotic agent, suggesting that inhibiting CYP1B1 or using trehalose derivatives could lead to new treatments for liver fibrosis.
Precision Medicine Strategies to Improve Isoniazid Therapy in Patients with Tuberculosis.
Eur J Drug Metab Pharmacokinet
September 2024
Department of Pharmacy Practice, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education (MAHE), Manipal, Karnataka, 576104, India.
Article Synopsis
- * Precision therapy for isoniazid involves using clinical and genomic data, including host pharmacogenomics (like NAT2 metabolism) and drug-resistance mutations in tuberculosis, to customize dosing for optimal patient outcomes.
- * Integrating various biological insights (like microbiome and epigenomics) alongside therapeutic drug monitoring can help adjust isoniazid dosages, reducing toxicity and enhancing effectiveness, but further research is needed for broader clinical application.
Pharmacogenomic associations of cyclophosphamide pharmacokinetic candidate genes with 4hydroxycyclophosphamide formation in children with Cancer.
Cancer Chemother Pharmacol
October 2024
Fred Hutchinson Cancer Center, Division of Public Health Sciences, Seattle, WA, 98109, USA.
Purpose: 4-hydroxycyclophosphamide (4HCY) is the principal precursor to the cytotoxic metabolite of cyclophosphamide (CY), which is often used as first-line treatment of children with cancer. There is conflicting data regarding the relationship between CY efficacy, toxicity, and pharmacokinetics with the genes encoding proteins involved in 4HCY pharmacokinetics, specifically its formation and elimination.
Methods: We evaluated germline pharmacogenetics in children with various malignancies receiving their first CY dose.
Urine metabolomics signature reveals novel determinants of adrenal suppression in children taking inhaled corticosteroids to control asthma symptoms.
Immun Inflamm Dis
July 2024
Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Article Synopsis
- The study investigates the relationship between inhaled corticosteroids (ICS) usage and adrenal suppression in asthma patients, as the risks associated with long-term glucocorticoid exposure are not well understood.
- Researchers analyzed 571 urine metabolites from 200 asthmatic children on ICS, categorizing them based on their plasma cortisol levels to identify potential biomarkers for adrenal status.
- Results revealed 90 metabolites linked to adrenal suppression, with notable differences in levels for certain steroids, and some metabolites like mannitol/sorbitol showed potential for further research, validated by additional studies.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!