Abstract
Aims
Two recent randomized controlled trials of type 2 diabetes mellitus (T2DM) patients with history of, or at high risk of, cardiovascular disease (CVD) showed no risk of ischemic cardiovascular events associated with dipeptidyl peptidase-4 inhibitors (DPP4i), but an increased risk of heart failure (HF) with saxagliptin. We evaluated the risk of CVD including myocardial infarction (MI), stroke, coronary revascularization, and HF associated with DPP4i in T2DM patients with and without baseline CVD as used in the community.
Methods
Using US commercial insurance claims data (2005–2012), we conducted a cohort study that included initiators of DPP4i and non-DPP4i treatments. Composite CVD endpoints including MI, stroke, coronary revascularization, and HF were defined with a hospital discharge diagnosis or procedure code. Cox proportional hazards models compared the risk of composite and individual CVD endpoints in propensity score (PS)-matched initiators of DPP4 versus non-DPP4i.
Results
We included 79,538 (18 % with baseline CVD) persons in PS-matched pairs of DPP4i and non-DPP4i initiators. The incidence rate per 1,000 person-years for composite CVD was 30.30 (95 % CI 28.24–32.51) in DPP4i and 34.76 (95 % CI 32.34–37.36) in non-DPP4i. The PS-matched hazard ratio (HR) for composite CVD was 0.87 (95 % CI 0.79–0.96) in DPP4i versus non-DPP4i. The PS-matched HR for HF was 0.81 (95 % CI 0.70–0.94) in DPP4i versus non-DPP4i. Among patients with baseline CVD, there was no increased risk of CVD or HF associated with DPP4i use.
Conclusions
Among T2DM patients, initiating DPP4i was not associated with a greater risk of CVD or HF compared to non-DPP4i initiators.
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Abbreviations
- CVD:
-
Cardiovascular disease
- DM:
-
Diabetes mellitus
- DPP4i:
-
Dipeptidyl peptidase-4 inhibitors
- HbA1c:
-
Glycated hemoglobin
- HF:
-
Heart failure
- HR:
-
Hazard ratio
- ICD-9 CM:
-
International Classification of Diseases, Ninth Revision, Clinical Modification 9th edition
- PS:
-
Propensity score
- RCT:
-
Randomized controlled trial
- T2DM:
-
Type 2 diabetes
- TZD:
-
Thiazolidinedione
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Acknowledgments
Kim was supported by the NIH grant K23 AR059677. Goldfine is supported by the NIH grants R56 DK095451, P50 HL083813, R01 DK088214, U01 HL101422, P30-DK03836, and American Diabetes Association 7-13-CE-17.
Conflict of interest
Kim received research support from Pfizer, Inc, Glynn received research grants from AstraZeneca and Novartis, Liu has no conflict of interest, Everett receives research support from Roche Diagnostics and Novartis and Goldfine receives research support in the form of materials and supplies from Amneal Pharmaceuticals; Lifescan, a Division of Johnson and Johnson; Novo Nordisk; Mercodia and Nestle, Inc.
Human and Animal Rights disclosure
The study protocol was approved by the Institutional Review Board of the Brigham and Women’s Hospital. All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008.
Informed consent disclosure
Patient informed consent was not required as the dataset was de-identified to protect subject confidentiality.
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Managed by Antonio Secchi.
Prior Presentation Parts of this study were presented in abstract form at the ICE/ENDO 2014 meeting in Chicago, IL, 21–24 June 2014.
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Kim, S.C., Glynn, R.J., Liu, J. et al. Dipeptidyl peptidase-4 inhibitors do not increase the risk of cardiovascular events in type 2 diabetes: a cohort study. Acta Diabetol 51, 1015–1023 (2014). https://doi.org/10.1007/s00592-014-0663-2
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DOI: https://doi.org/10.1007/s00592-014-0663-2