Dr. Dimas Adhi Pradana, a distinguished lecturer in the Department of Pharmacy at the Faculty of Mathematics and Natural Sciences, Islamic University of Indonesia, has achieved a significant milestone by completing his doctoral program at Universitas Gadjah Mada (UGM).
His journey culminated in a successful defense of his dissertation on the “Influence of Genetic Variation SLC22A1 rs628031 on the Population-Based Pharmacokinetics/Pharmacodynamics of Metformin: An Indirect Response Model Study in Javanese Type 2 Diabetes Mellitus (DM) Patients.”
In his dissertation, Dr. Pradana delved into the critical issue of suboptimal therapeutic effects observed in many patients initiating metformin monotherapy for type 2 diabetes.
Drawing from a thorough examination of existing studies, he uncovered reports indicating that the drug’s efficacy fell short of the optimal mark in a significant subset of patients.
“Approximately 40 percent of patients fail to achieve the therapeutic target within the first three months of metformin treatment,” he said during his presentation at the UGM Faculty of Medicine, Public Health, and Nursing on Friday (Dec. 8).
“Several factors contributing to variations in metformin therapy response encompass genetic variances in transporters, body mass index (BMI), kidney function, age, gender, medication adherence, nutritional diet, and exercise.”
Dr. Pradana elucidated that genetic variations in organic cation transporter 1 (OCT1) are pivotal in the heterogeneous responses to metformin therapy.
OCT1, a crucial transporter for metformin, exhibits heightened expression in the liver, dwelling on the sinusoidal membrane of hepatocytes and the plasma membrane of cholangiocytes.
OCT1 is also prevalent in the ileum, particularly on the lateral membrane of enterocytes and on the apical and subapical domains of proximal and distal tubules in the kidneys.
Genetic variations in the Solute Carrier Family 22A1 (SLC22A1) gene, the guardian of OCT1, reduce its functionality as a transporter, hampering metformin’s transit into the systemic circulation from enterocytes and hepatocytes.
The overarching goal of Dr. Pradana’s research was to scrutinize the impact of genetic variations in the SLC22A1 rs628031 gene, governing the OCT1 transporter, on the population-based pharmacokinetics/pharmacodynamics (PK/PD) of metformin and the ensuing therapeutic response after a 12-week follow-up.
This inquiry aimed to provide insights into the interplay of pharmacogenetics and PK/PD metformin, elucidating the variances in therapy response through a PK/PD lens.
“Specifically, this study seeks to establish the frequency distribution of the SLC22A1 rs628031 A>G (Met408Val) gene variation in Javanese type 2 diabetes patients undergoing metformin monotherapy,” he clarified.
Dr. Pradana underscored that the study encompassed 123 participants newly diagnosed with type 2 diabetes and administered metformin monotherapy at a dosage of 2×500 mg.
He aspires to have his dissertation prove instrumental in advancing the realms of pharmacogenomics, pharmacokinetics, and pharmacodynamics about metformin, emerging as a touchstone for optimizing therapy for type 2 diabetes patients in Indonesia.
While acknowledging the accomplishment, Dr. Pradana emphasized the imperative of further research on additional transporter genes associated with metformin.
A comprehensive pharmacogenomic panorama of metformin in the Javanese population remains a quest for future exploration. Additionally, research spotlighting the efficacy of metformin therapy in patients grappling with insulin resistance demands further cultivation.
Author: Agung Nugroho