Sulfonylurea and Cancer Risk Among Patients With Type 2 Diabetes: A Population-Based Cohort Study

Abstract

BackgroundCurrent evidence of the association between the use of sulfonylurea and cancer risk is highly conflicting and little evidence of this association is from the mainland Chinese population. This study aimed to evaluate the potential effects of sulfonylurea use on cancer risk among patients with type 2 diabetes mellitus (T2DM).MethodsA retrospective cohort study of T2DM patients who were new users of sulfonylurea or metformin was conducted using the Yinzhou Regional Health Care Database. A marginal structural Cox model was used to estimate the hazard ratio (HR) of cancer associated with the use of sulfonylurea compared with metformin, with time-varying confounders controlled by inverse probability weighting. Secondary analyses using different glucose-lowering drugs (GLDs) as comparator and sensitivity analyses for potential bias due to latency period, model misspecification, missing data, analyses strategy (intention-to-treat and per-protocol), and diagnosis validation were performed to examine the robustness of the results.ResultsAfter fully controlling for time-varying confounding, baseline confounding, and competing risk, the use of sulfonylurea was not associated with the risk of any cancer (HR 1.09; 95% CI, 0.93–1.27), compared with the use of metformin. In the secondary analyses, compared with α - glucosidase inhibitors, thiazolidinediones, glinides, other GLDs except sulfonylure and insulin, and T2DM patients not treated with sulfonylureas, the HRs of the association between sulfonylurea use and cancer risk were 0.92 (95% CI; 0.78–1.08), 0.89 (95% CI; 0.66–1.19), 0.85 (95% CI; 0.71–1.02), 1.04 (95% CI; 0.89–1.22), and 1.07 (95% CI; 0.99–1.16), respectively. The results of analyses for various subgroups, risk of site-specific cancers, cumulative duration, dose-response relationship, and sensitivity analyses of different latency periods and missing data were generally consistent with the findings of the primary analyses.ConclusionNo association between sulfonylurea use and cancer risk was found in this study after properly controlling biases due to time-varying confounders and other sources. Further studies on the association between sulfonylurea use and the risk of cancer by using data from a Chinese population with higher representativeness are needed.

Thiazolidinedione use and risk of Parkinson’s disease in patients with type 2 diabetes mellitus

“…In this study we applied an active-comparator new-user (ACNU) design using AGIs which were another class of commonly used second-line hypoglycemic drugs in the study population 27 as the comparator, with a rich set of potential confounders, including lifestyle factors and disease severity measures, thus mitigating time-related bias and confounding by indication 25 , 28 . However, despite these epidemiological studies, clinical trials investigating effects of TZDs on PD risk are scarce.…”

“…Participants were drawn from the Yinzhou Regional Health Care Database (YRHCD), which integrated longitudinal information of electronic medical records, disease registry and management, death registry and other healthcare services in the Yinzhou District, Ningbo City of China 27 , 30 . In 2008, disease registry and management systems were established for diabetes mellitus, cancer, cardiovascular disease, hypertension, and chronic obstructive pulmonary disease.…”

“…In 2008, disease registry and management systems were established for diabetes mellitus, cancer, cardiovascular disease, hypertension, and chronic obstructive pulmonary disease. Diabetes patients were registered in the disease surveillance system once diagnosed and would be followed up at least four times a year by community physicians, with common health measures, including blood pressure, fasting plasma glucose (FPG), glycated hemoglobin (HbA1c) being measured or asked 27 . In this study, disease registry system and electronic diagnosis records were linked and patients with T2DM were included if they: (1) were registered in the diabetes registry system and diagnosed with T2DM; or (2) had more than two diagnosis records of T2DM and no records of type 1 diabetes in the electronic medical records.…”

Thiazolidinedione use is associated with reduced risk of dementia in patients with type 2 diabetes mellitus: A retrospective cohort study

“…We assembled a retrospective cohort of new users of TZDs and alpha glucosidase inhibitors (AGIs) using the Yinzhou Regional Health Care Database (YRHCD). The YRHCD integrated longitudinal information of electronic medical records, disease registry and management, death registry, and other healthcare services in the Yinzhou District, Ningbo City of China 21,22 . Diabetes patients were registered in the disease registry system and would be followed up quarterly by community physicians, with common health measures, such as c(FPG) and glycated hemoglobin (HbA1c), being measured or asked 22 .…”

“…Information of drug exposure, covariates, and outcome was extracted through linking longitudinal records of drug prescription, laboratory examination, and outpatient and inpatient visits. The data used in this study and their relationship were presented in Figure S1 and have been outlined in detail previously 22 …”