Era's Lucknow Medical College and Hospital - Interindividual Variation in Efficacy of Metformin in Type 2 Diabetes

Q: How was metformin response defined in the study?

Response to metformin was defined using HbA1c levels. Patients were divided into responders (HbA1c < 7%) and non-responders (HbA1c ≥ 7%).

Q: What was the association between OCT1 rs628031 and metformin response?

No significant association was found between OCT1 (rs628031) polymorphism and metformin response in the studied T2DM patients.

Q: Why is OCT3 rs2292334 important for metformin therapy?

The study found a significant association between OCT3 rs2292334 polymorphism and metformin response, and suggests OCT3 genotyping could help predict response in T2DM patients.

Sep 24, 2026

Uploaded by Miles

Interindividual variation in metformin efficacy among type 2 diabetes mellitus (T2DM) patients has been linked to genetic variants. This study evaluates how pharmacogenetic polymorphisms in organic cation transporter genes OCT1 and OCT3 influence drug response in a North Indian population. OCT1 rs628031 and OCT3 rs2292334 were genotyped using PCR-RFLP, and response was defined by HbA1c levels, comparing responders versus non-responders. No significant OCT1 association was observed, while OCT3 rs2292334 showed significant links to metformin response, suggesting OCT3 genotyping may support predictive, more personalized therapy.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages13

Reading Time33 min

AccessFree to download

Background

Metformin and T2DM treatment

Genetic factors and personalized therapy

Study Methods

Study design and participants

Genotyping and response definition

Results

OCT1 rs628031 findings

OCT3 rs2292334 findings

Conclusion

Predicting metformin response using OCT3

􀂦 Era University Era's Lucknow Medical College and Hospital Era's Lucknow Medical College and Hospital Anti-diabetic drugs, Metformin, Organic Cation Transporter, Pharmacogenetics, Single Nucleotide Polymorphism, Type 2 Diabetes Mellitus August 9th, 2023 [https://doi.org/10.21203/rs.3.rs-3227562/v1](https://doi.org/10.21203/rs.3.rs-3227562/v1) 􀁱 􀅏 This work is licensed under a Creative Commons Attribution 4.0 International License. Read Full License Interindividual variation in e¨cacy of metformin among type 2 diabetes mellitus (T2DM) patients have been associated with several genetic variants. Understanding the genetic pathways involved in pharmacodynamics of metformin can affect personalized treatment of T2DM. Our study aimed to ¦ nd the implication of genetic polymorphism in organic cation transporters OCT1 and OCT3) genes on drug e¨cacy of metformin therapy in T2DM patients from North India. This study evaluated the role of OCT1 (rs628031) and OCT3 (rs2292334) polymorphism in metformin response on T2DM patients. Response to metformin was de¦ ned by HbA1c levels based on which patients (n = 177) were divided into two groups: responders (HbA1C < 7% ; n = 127) and non-responders (HbA1C ≥ 7%; n = 50) . The responders were further subcategorized as T2DM patients on monotherapy (n = 55) and on combination therapy (n = 72) . Genotyping was done using PCR-RFLP approach. No signi¦cant association was found between OCT1 (rs628031) polymorphism and metformin response in T2DM patients. On the other hand, signi¦cant association of OCT3 (rs rs2292334) polymorphism was observed with metformin response where AA genotype carriers showed higher e¨cacy of metformin both in mono [OR (CI) = 0.29(0.11–0.72) and p = 0 .007] and combination therapy [OR (CI) = 0 .41(0.16-1.0) and p = 0 .047]. Also, A allele was more prevalent in responders [OR (CI) = 0 .48(0.28–0.84) and p = 0 .010] while G allele was found to be associated withine¨cacy of metformin in T2DM patients [OR (CI) = 2 .07(1.19–3.61) and p = 0 .010]. Genotyping of OCT3 (rs2292334) might be useful in predicting the response to metformin in T2DM patients. Type 2 Diabetes Mellitus (T2DM) is a complex metabolic disorder with multiple etiologies including genetic and environmental risk factors. It has emerged as a global epidemic in the past few decades where the number of T2DM cases in 2021 were 536.6 million and the ¦gures are expected to rise to 783.2 million by 2045[1]. There are different treatment options available for T2DM management with metformin monotherapy being generally preferred as the ¦ rst line of treatment. However if it fails to control the blood glucose levels, then a dual or combination therapy of metformin and sulfonyl ureas is usually prescribed to patients together. Research conducted globally have shown abetter effect of combination therapy in lowering blood glucose levels compared to monotherapy [2]. The clinical etiology, presentation and complications of T2DM vary from person to person which make the management of T2DM a much more challenging task for clinicians even after having several treatment options. Long-standing uncontrolled glucose levels have been found to be associated with various micro vascular damage and complications in the eyes, kidneys, nerves and heart thus affecting the quality of life ultimately resulting in death in most cases. The difference in response to oral hypoglycemic drugs amongst T2DM patients pose a major hurdle in disease management and interestingly up to 40% of these inter-individual variabilities are affected by genetic factors [3]. Based on the contribution of multiple genetic factors in the etiology of T2DM and variable response to different anti-diabetic agents, genetic architecture of each individual alter their treatment e¨cacy and drug response. Using genetic information and calculating a genetic risk score, based on different genetic variants, may enable us toreclassify patients with T2DM in d

FAQs

How was metformin response defined in the study?

Response to metformin was defined using HbA1c levels. Patients were divided into responders (HbA1c < 7%) and non-responders (HbA1c ≥ 7%).

What was the association between OCT1 rs628031 and metformin response?

No significant association was found between OCT1 (rs628031) polymorphism and metformin response in the studied T2DM patients.

Why is OCT3 rs2292334 important for metformin therapy?

The study found a significant association between OCT3 rs2292334 polymorphism and metformin response, and suggests OCT3 genotyping could help predict response in T2DM patients.

Sep 24, 2026

Uploaded by Miles