PhD Researcher University of Groningen Voorburg, Netherlands
Background: Metformin has been found to inhibit serotonin uptake by organic cation transporters (OCT1 and OCT2), which suggests the serotonergic pathway playing a role in its mechanism of action. The serotonin transporter (5-HTT) has been associated with metformin intolerance, but its role in impacting HbA1c was inconclusive.
Objectives: To investigate and expand on earlier investigations on 5-HTTLPR genotype on the impact of metformin in T2D patients in a longitudinal study.
Methods: The Hoorn Diabetes Care System (DCS) cohort is a prospective longitudinal cohort of primary care patients with diabetes where clinical measures are collected annually. For this investigation, the primary outcome is to determine change in HbA1c level from baseline to the annual visitations by the patient, stratified by 5-HTTLPR genotype.
Patient characteristics were summarised using descriptive statistics, stratified per 5-HTTLPR genotypes. ANOVA was conducted to test for statistical differences in these characteristics between the genotype groups. For the first analysis, ANCOVA will be conducted to determine the 5-HTT genotypes (5-HTTLPR) were associated with the change in HbA1c level over one year after metformin initiation, as part of the replication of an earlier study. For the second, a linear mixed effect model to determine whether 5-HTTLPR status demonstrates significance on HbA1c level over the study time period.
Results: The preliminary analysis was conducted on a subset of the participants (n = 589), of which 57% (n = 334) were female. The average age was 61.9 ± 10.4 years and mean baseline HbA1c was 6.9% ± 1.3%. 5-HTTLPR was characterized in 172 patients as L*L*, 263 patients as L*S* and 154 patients as S*S* genotypes. Further analysis is ongoing and will be completed in upon final data linkage is achieved.
Conclusions: The patient cohort is representative of patients who were recently diagnosed with T2D in the Netherlands. With the limited number of studies evaluating the impact of genotype on longitudinal outcomes in T2D patients, this study expects to shed an exploratory light on the benefit of incorporating genetic testing for drug monitoring.
