Glucagon-like peptide receptor agonists (GLP-1 RAs) and dipeptidyl peptidase-4 (DPP-4) inhibitors are medications commonly prescribed to patients with type 2 diabetes (high blood sugar levels). Aside from their ability to effectively manage sugar levels in the body, these drugs have been shown to have several other clinical benefits. There is experimental evidence that these drugs can reduce the growth of uterine cancer cells in laboratory studies. However, it remains unknown whether these drugs are protective against cancer of the uterus using real-world data. Therefore, using a large population-based cohort, the goal of this study is to investigate the potential association between these drugs and the risk of uterine cancer among patients with type 2 diabetes. Seeing as type-2 diabetes is a high-risk factor for uterine cancer in females, the results of this study may render important clinical implications and support the use of these drugs for prevention of uterine cancer.
Glucagon-like peptide receptor agonists (GLP-1 RAs) and dipeptidyl peptidase-4 (DPP-4) are anti-hyperglycemic agents commonly prescribed to patients with type 2 diabetes. These incretin-based drugs are known to have several beneficial pleiotropic effects including their ability to induce weight loss and lower the risk of hypoglycemia and cardiovascular events. Consequently, they are being proposed as preventative treatments and therapies for pathologies outside of the pancreas. There is novel experimental evidence that these drugs can inhibit the growth of endometrial cancer cells in vitro; however, there remains limited research on the association between the use of incretin-based drugs and the incidence of endometrial cancer in a real-world setting. Therefore, using a large population-based cohort from the Clinical Practice Research Datalink, the goal of this study is to investigate whether the use of GLP-1 RAs and DPP-4 inhibitors, separately, is associated with a decreased risk of endometrial cancer in females with type 2 diabetes. To do so, the study will compare incident users of either GLP-1 RAs or DPP-4 inhibitors with incident users of sulfonylureas from January 01, 2007 to December 31, 2021, with follow-up until December 31,2022. Propensity score fine stratification weighting will be used to control for confounding and hazard ratios with corresponding 95% confidence intervals will be estimated using Cox proportional hazard models. Visualization of the cumulative incidence of endometrial cancer for each exposure group will be displayed using weighted Kaplan-Meier curves. Seeing as obesity, insulin-resistance and diabetes are high risk factors for endometrial cancer, the results of this study may render significant clinical implications pertaining to the use of incretin-based drugs for chemoprevention of endometrial cancer in individuals with type 2 diabetes.
An incident diagnosis of endometrial cancer, as determined by pre-specified Read codes, will be the primary outcome of interest. Endometrial cancer is well-recorded in the CPRD with a high positive predictive value (PPV); a validation study showed that 100% of endometrial cancer cases identified between 2004-2012 in the CPRD by Read diagnostic codes were confirmed by through clinical review of patient profiles.15 Endometrial cancer events occurring in the first year of follow-up will be censored as non-events in order to account for latency (i.e., as early events are unlikely associated with the exposure) and detection bias (i.e., there may be more frequent contact with the healthcare system in the weeks to months after initiation of a new drug therapy).
Samy Suissa - Chief Investigator - Sir Mortimer B Davis Jewish General Hospital
Laurent Azoulay - Corresponding Applicant - McGill University
Hui Yin - Collaborator - Sir Mortimer B Davis Jewish General Hospital
Sonny Rothman - Collaborator - McGill University
HES Admitted Patient Care;Patient Level Index of Multiple Deprivation