University Honors

Obesity and type-2-diabetes mellitus (T2DM) are associated with increased malignancy risk. Glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose cotransporter 2 inhibitors (SGLT-2i) are increasingly used for diabetes management, but their association with cancer-risk is poorly defined. Here we compared all-cause or obesity-associated cancer (OAC) incidence among diabetics treated with first-line therapy (FLT) versus GLP-1RA or SGLT-2i. Using the TriNetX US Collaborative Network, T2DM adults (ICD-10 E11) were categorized into 3 groups- FLT (dipeptidyl peptidase-4 inhibitor or metformin) excluding GLP-1RA and SGLT-2i, or GLP-1RA or SGLT2i plus FLT- based on first recorded exposure to medication (index event). Insulin usage and cancer diagnosis before the index event was excluded. Primary and secondary outcomes were incident diagnosis of any malignant neoplasm (ICD-10 C00-C96) or OAC, respectively. Cohorts were balanced using propensity score matching and hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using Kaplan-Meier analyses. GLP-1RA and SGLT-2i were associated with a reduced risk of all-cancer risk compared to FLT. Compared to the FLT cohort which had an increased risk of 76.1%, the GLP-1RA cohort showed an approximate risk of 70.3% and the SLGT-2i cohort showed a risk of around 66.0%. The GLP-1RA cohort also had a hazard ratio (HR) of 0.934 and a relative risk ratio (RR) of 0.924. The SGLT-2i cohort resulted in a HR value of 0.862 and a RR value of 0.878. Based on the risk (%) as well as HR and RR values, SGLT-2i shows a greater protective effect compared to GLP-1RA. As for the secondary outcome of OAC, there were consistent reductions across several cancers. The risk reductions were substantial and ranged from 25% to 40%. Notably, SLGT-2i showed slightly stronger associations across various cancers. From this study, it is shown that cancer risk is decreased in cohorts of patients that are being treated with newer anti-diabetic therapies compared to patients that are on FLT exclusively. Both GLP-1RA and SGLT-2i showed a decreased risk but SGLT-2i seemed to have a stronger effect. The longitudinal effects of this study still remains unclear as there were some time-to-event analyses that were less consistent across cancers. Ultimately this study can be used to create more personalized therapeutic treatments, particularly for patients at a higher risk for OAC.