Evaluation of PRKAA2 Genetic Variation on Metformin Efficacy as an Initial Therapy Among Drug-Naïve Patients With Type II Diabetes Mellitus

Background: Metformin is the most popular oral antidiabetic agent, which is recommended as initial monotherapy. AMPK is the pivotal target of metformin molecular mechanisms. AMPK subunit a2 (encoded by PRKAA2 ) is a gene contributable to increase type 2 diabetes mellitus (T2DM) risk. This study aimed to evaluate PRKAA2 rs2796498, rs2746342, and rs980799 genetic variations on metformin efficacy. Methods: : This study enrolled 191 newly diagnosed Indonesia T2DM patients in primary health care. Patients who received metformin as monotherapy for at least 3 months were included for genotyping. Genotyping was performed using the Taqman assay. Results: : Baseline characteristics showed that BMI was higher among AA than GG+AG (p=0.04). Patients with TT genotype showed a higher FBG and HbA1c than GG+GT (p=0.02 and p=0.02, respectively). There was no significant difference in allele and genotype frequencies between responders and non-responders group in PRKAA2 rs2796498, rs9803799, and rs2746342. However, among PRKAA2 rs2796498, AG carrier had 0.32 times of responding in metformin efficacy after adjusting BMI, WC, blood pressure, lipid profiles, and eGFR. Dominant model of rs2796498 showed a significant association (OR=0.34, 95%CI=0.13 – 0.90) to metformin efficacy. Conclusions: : Our findings suggest that PRKAA2 rs2796498 genetic variation may affect metformin efficacy, especially AG carrier, in drug-naïve T2DM patients.