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Abstract
Introduction This study aims to compare the risks of cancer among patients with type 2 diabetes mellitus (T2DM) on metformin–sulfonylurea dual therapy intensified with dipeptidyl peptidase 4 inhibitors (DPP4i), thiazolidinediones, or insulin.
Research design and methods We assembled a retrospective cohort data of 20 577 patients who were free of cancer and on metformin–sulfonylurea dual therapy, and whose drug treatments were intensified with DPP4i (n=9957), insulin (n=7760), or thiazolidinediones (n=2860) from January 2006 to December 2017. Propensity-score weighting was used to balance out baseline covariates across the three groups. HRs for any types of cancer, cancer mortality, and all-cause mortality were assessed using Cox proportional-hazards models.
Results Over a mean follow-up period of 34 months with 58 539 person-years, cumulative incidences of cancer, cancer mortality, and all-cause mortality were 0.028, 0.009, and 0.072, respectively. Patients intensified with insulin had the highest incidence of all-cause mortality (incidence rate=3.22/100 person-years) and the insulin itself posed the greatest risk (HR 2.46, 95% CI 2.25 to 2.70, p<0.001; 2.44, 95% CI 2.23 to 2.67) compared with thiazolidinediones and DPP4i, respectively. Comparing between thiazolidinediones and DPP4i, thiazolidinediones was associated with higher risk of cancer (HR 1.43, 95% CI 1.25 to 1.63) but not cancer mortality (HR 1.21, 95% CI 0.92 to 1.58) and all-cause mortality (HR 0.99, 95% CI 0.88 to 1.11). Insulin was associated with the greatest risk of cancer mortality (HR 1.36, 95% CI 1.09 to 1.71; 1.65, 95% CI 1.31 to 2.07) compared with thiazolidinediones and DPP4i, respectively.
Conclusions For patients with T2DM on metformin–sulfonylurea dual therapy, the addition of DPP4i was the third-line medication least likely to be associated with cancer mortality and cancer effect among three options, and posed no increased risk for all-cause mortality when compared with thiazolidinediones.
- insulin
- cancer
- type 2 diabetes
- thiazolidinediones
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Footnotes
Contributors CKHW had the original idea for the study, contributed to the development of the study, reviewed the literature, constructed the study design, conducted the statistical analysis, wrote the first draft of the manuscript, and acts as guarantor for the study. CKHW, KKCM, and TW provided critical input to the statistical analyses and design. EWYC, ICKW, and CLKL provided critical input to the study design. ETYT provided critical input to the diagnosis and drug dispensing codes from the database. All authors contributed to the interpretation of the analysis, critically reviewed and revised the manuscript, and approved the final manuscript as submitted. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted.
Funding This study was funded by the Health and Medical Research Fund Research Fellowship Scheme, Food and Health Bureau, Hong Kong SAR (Ref No. 02160087).
Disclaimer No funding organization had any role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation of the manuscript.
Competing interests CKHW reports receipt of research funding from the EuroQoL Group Research Foundation, the Hong Kong Research Grants Council, and the Hong Kong Health and Medical Research Fund. KKCM reports receipt of CW Maplethorpe Fellowship and personal fee from IQVIA Ltd. EWYC reports receipt of research funding from Bristol-Myers Squibb, Pfizer, Janssen, Takeda Pharmaceuticals, the Hong Kong Beat Drugs Fund Association, the Hong Kong Research Grants Council, and the Hong Kong Health and Medical Research Fund. ICKW reports receipt of research funding from Bristol-Myers Squibb, Pfizer, Janssen, the Hong Kong Research Grants Council, and the Hong Kong Health and Medical Research Fund. CLKL reports receipt of research funding from the Hong Kong Research Grants Council, the Hong Kong Health and Medical Research Fund, and the Kerry Group and Kouk Foundation Endowed Primary Care Research Fund of the University of Hong Kong. No other disclosures were reported.
Patient consent for publication Not required.
Ethics approval All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Ethics approval of this study was granted by Institutional Review Board of the University of Hong Kong/Hospital Authority Hong Kong West Cluster (Ref No. UW 16-1018).
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement The database was obtained from the Hong Kong Hospital Authority Head Office (a third party), and is not publicly available. For further information on the access to the database, please contact Central Panel on Administrative Assessment of External Data Requests, Hong Kong Hospital Authority Head Office (hacpaaedr@ha.org.hk). The codes used to produce and analyze the data will be available from the corresponding author on request.