Editorial,  Endocrinol Diabetes Res Vol: 11 Issue: 4

Metformin Pharmacogenomics: Genetic Determinants of Drug Response in Diabetes Management

Dr. Noor Al-Hassan^*

Dept. of Clinical Pharmacology, Doha Medical University, Qatar

*Corresponding Author:

Dr. Noor Al-Hassan
Dept. of Clinical Pharmacology, Doha Medical University, Qatar
E-mail: n.alhassan@dmu.qa

Received: 01-Aug-2025, Manuscript No. ecdr-26-182689; Editor assigned: 4-Aug-2025, Pre-QC No. ecdr-26-182689 (PQ); Reviewed: 19-Aug-2025, ecdr-26-182689; Revised: 26-Aug-2025, Manuscript No. ecdr-26-182689 (R); Published: 30-Aug-2025, DOI: 10.4172/2324-8777.1000442

Citation: Noor A (2025) Metformin Pharmacogenomics: Genetic Determinants of Drug Response in Diabetes Management. Endocrinol Diabetes Res 11:442

Introduction

Metformin is the first-line therapy for type 2 diabetes mellitus due to its efficacy in lowering blood glucose, favorable safety profile, and beneficial effects on weight and cardiovascular risk. Despite its widespread use, there is considerable interindividual variability in glycemic response, gastrointestinal tolerance, and risk of adverse effects. Pharmacogenomics, the study of how genetic variations influence drug response, has emerged as a key tool for understanding these differences. Investigating metformin pharmacogenomics can inform personalized diabetes treatment and optimize therapeutic outcomes [1,2].

Discussion

Metformin primarily acts by reducing hepatic gluconeogenesis and enhancing peripheral insulin sensitivity. Its pharmacokinetics and pharmacodynamics are influenced by various transporters and metabolic pathways, many of which are encoded by genes exhibiting functional polymorphisms. The organic cation transporter 1 (OCT1), encoded by the SLC22A1 gene, is critical for hepatic uptake of metformin. Variants in SLC22A1 can reduce transporter function, leading to diminished drug accumulation in the liver and attenuated glucose-lowering effects. Similarly, polymorphisms in SLC22A2 (OCT2), which regulates renal clearance, can affect metformin excretion and systemic exposure [3,4].

Another important transporter is MATE1 (encoded by SLC47A1), involved in metformin efflux from hepatocytes and renal tubular cells. Genetic variants in SLC47A1 influence plasma drug concentrations and treatment efficacy. In addition to transporter genes, polymorphisms in AMP-activated protein kinase (AMPK) pathways may modulate metformin’s action on glucose metabolism, although these associations require further validation [5].

Pharmacogenomic studies have also identified ethnic differences in metformin response linked to allele frequencies of key transporter genes. For example, certain loss-of-function variants in SLC22A1 are more prevalent in European populations, correlating with reduced drug efficacy. Understanding these genetic influences can guide clinicians in dose adjustment, combination therapy selection, and early identification of non-responders.

Despite promising findings, integrating pharmacogenomics into routine clinical practice faces challenges. Many studies are limited by small sample sizes, heterogeneous populations, and inconsistent outcome measures. Moreover, genetic factors account for only a portion of the variability in metformin response, with environmental and lifestyle factors also playing significant roles.

Conclusion

Metformin pharmacogenomics offers valuable insights into the genetic determinants of drug response in type 2 diabetes, highlighting the potential for personalized therapy. Variants in transporter and signaling pathway genes can influence efficacy, tolerability, and optimal dosing. Continued research and large-scale validation studies are essential to translate pharmacogenomic knowledge into clinical practice, enabling precision medicine approaches that improve glycemic control and minimize adverse effects in diverse patient populations.

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