Association of FTO Gene Variant (rs9939609) with Antidiabetic Drug Response in Patients with Type 2 Diabetes Mellitus (T2DM)

Objective: Our earlier work demonstrated that the FTO gene variant rs9939609 not only predicts cardiovascular disease risk but also has a strong association with diabetes-related micro-and macrovascular complications. In this study, we evaluated the therapeutic response to antidiabetic drugs in individuals with type 2 diabetes mellitus (T2DM), stratified by their FTO rs9939609 genotypes. Methodology: After obtaining ethical approval, this three-month prospective cohort study was conducted at Sheikh Zayed Medical College & Hospital, Rahim Yar Khan. A total of 140 T2DM patients with and without cardiovascular disease (CVD) were enrolled. All participants, of either gender and taking antidiabetic medications were followed for a period of three months. The therapeutic response was evaluated based on glycemic control, primarily through changes in HbA1c levels. Results: In our study, 66% of participants were male and 34% were female. Non-responders had a significantly longer duration of type 2 diabetes mellitus (T2DM), with a mean duration of 7.6 years compared to 6.2 years in responders (p = 0.002). Based on their therapeutic response, 76 (54.3%) patients were classified as responders while 64 (45.7%) were classified as non-responders. Statistical analysis showed no significant difference between responders and non-responders in genotype distribution (p = 0.404) or allele frequencies (p = 0.500). Furthermore, when assessing the association between the FTO gene rs9939609 genotypes and response to different classes of antidiabetic medications, no significant differences in genotype or allele frequencies were observed between the two groups (p > 0.05). Conclusion: Our study revealed no significant association between treatment response and the FTO rs9939609 genotypes or alleles. However, individuals with the AA genotype and risk allele (A) exhibited substantially higher levels of HbA1c and fasting blood glucose (FBG) as compared to other genotypes.