Research Projects

Study Rationale: The current treatment options for diabetes range from metformin, sulfonylureas, glitazones, gliptins, gliflozins, among other oral agents. Though metformin is generally the preferred initial drug of choice, early combination therapy can also be considered in certain subset of population so as to extend the time to treatment failure. In this regard, depending on cardiovascular and renal comorbidities, efficacy, hypoglycemia risk, impact on weight, cost, risk for side effects, and patient preferences, gliptins are co-prescribed. Compared to the Non-Asian cohort, Indian patients respond more favorably with gliptins. Saxagliptin, sitagliptin, vildagliptin, linagliptin, gemigliptin, and teneligliptin are currently available in the Indian market. However, the response to gliptins varies from individual to individual and the same can be due to differential expression of genes involved in the pharmacodynamics and pharmacokinetics of gliptins. Primary Objective: •To assess the effect of GLP1R, CDKAL1, GIPR, KCNQ1, DPP-4, KCNJ11, CTRB1/CTRB2, and PRKD1 gene polymorphisms on the relative change in HbA1c and fasting blood glucose in type 2 diabetes mellitus patients of South India who are taking gliptins as monotherapy or add-on. Secondary Objectives: • To assess the effects of these SNPs on dose requirement of gliptins for glycemic control. • To assess the effects of these SNPs on adverse effects of gliptins. Methods: Patients will be enrolled based on their eligibility criteria in the study after obtaining written informed consent. Baseline and demographic characteristics of the patients such as age, gender, weight and height will be recorded. HbA1c shall be measured at baseline and after three months. FBG shall be measured at baseline and monthly for the next three months. The duration of diabetes, type and dosage schedule of concerned gliptin and adverse effects related to gliptin use would also be recorded. Five mL of venous blood will be collected from the participants. A kit-based method will be used for extracting adequate amounts of DNA. The quality and quantity of the extracted DNA will be assessed. The SNPs (n = 10) as stated in the objectives will be genotyped using Applied Biosystems Real-Time PCR System using validated TaqMan® SNP genotyping assay method. Allelic discrimination will be done by Sequence Detection Software (SDS). The genotype and allele frequencies will be ascertained by direct gene count method. The absolute and relative change in HbA1c shall be computed and assessed across the genotype groups. The incidence and severity of ADRs would also be analyzed across the genotype groups. Implications: •The implication of this study is to ascertain if there are pharmacogenetic differences with regards to therapeutic response of gliptins in our ethnically distinct South Indian cohort. •Further, through this study, the allele and genotype frequency of the studied SNP variants can be established in our population.