OR34-6 Dipeptidyl Peptidase-4 Inhibitors Do Not Increase the Risk of Cardiovascular Events in Type 2 Diabetes: A Population-Based Cohort Study

Program: Abstracts - Orals, Poster Preview Presentations, and Posters
Session: OR34-Predictors and Mediators of Cardiovascular Risk: Clinical Research
Monday, June 23, 2014: 11:30 AM-1:00 PM
Presentation Start Time: 12:45 PM
W184 (McCormick Place West Building)
Seoyoung C. Kim, MD1, Robert Glynn, PhD1, Jun Liu1, Brendan M. Everett, MD1 and Allison B Goldfine, MD2
1Brigham and Women's Hospital, Boston, MA, 2Joslin Diabetes Center, Boston, MA
Dipeptidyl peptidase-4 inhibitors (DPP4i), such as linagliptin, saxagliptin, and sitagliptin, are oral glucose-lowering drugs for type 2 diabetes mellitus (T2D). While two recent large clinical trials of T2D patients with cardiovascular disease (CVD) at baseline showed no risk of ischemic cardiovascular events associated with DPP4i, one trial showed an increased risk of hospitalization for heart failure (HF) in the saxagliptin group. The objective of this study was to evaluate the risk of CVD including myocardial infarction (MI), stroke, coronary revascularization, and HF associated with DPP4i in T2D patients with and without baseline CVD.

We conducted a population-based cohort study using commercial insurance claims data (2005-2012). Among patients aged 40 years and older with T2D, two mutually exclusive exposure groups were selected: 1) DPP4i combotherapy (DPP4i plus metformin) and 2) non-DPP4i combotherapy (metformin plus other non-DPP4i drugs) initiators. Patients with cancer, end-stage renal disease, dialysis, or use of insulin-containing drugs or glucagon-like peptide 1 agonists at baseline were excluded. The primary endpoint was a composite CVD outcome including MI, stroke, coronary revascularization and HF, defined with a hospital discharge diagnosis or procedure code. The secondary endpoints were the individual components of the primary endpoint. To control for baseline confounders such as demographic factors, comorbidities, medications, and health care utilization, propensity score (PS) matching method was used. PS-matched Cox regression models compared the risk of CVD in DPP4i initiators compared to non-DPP4i initiators with and without baseline CVD. Sensitivity analysis compared initiators of DPP4i monotherapy versus non-DPP4i monotherapy.  We included a total of 32,419 (5,573 pairs with baseline CVD and 26,746 without) PS-matched pairs of DPP4i and non-DPP4i combotherapy initiators. Among patients with baseline CVD, the IR per 1,000 person-years for composite CVD was 86.2 (95%CI 77.2-96.2) in DPP4i and 100.5 (95%CI 89.8-112.6) in non-DPP4i. The PS-matched HR for composite CVD was 0.90 (95%CI 0.77-1.06) for DPP4i vs. non-DPP4i combotherapy initiators in patients with baseline CVD. Among patients with no baseline CVD, the IR per 1,000 person-years for composite CVD was 15.9 (95%CI 14.2-17.9) in DPP4i and 17.0 (95%CI 15.0-19.3) in non-DPP4i. The PS-matched HR for composite CVD was 0.95 (95%CI 0.80-1.13) in patients with no baseline CVD for DPP4i vs. non-DPP4i initiators. The PS-matched HR for hospitalization for HF was also not increased with DPP4i. Similarly, the sensitivity analysis showed no increased CVD risk in DPP4i monotherapy initiators with and without baseline CVD.  

In conclusion, in this large cohort of T2D patients, initiating DPP4i was not associated with an increased or decreased risk of CVD including HF compared to those initiating non-DPP4i.

Disclosure: SCK: Investigator, Pfizer, Inc.. ABG: Principal Investigator, Daiichi Sankyo, Principal Investigator, Novo Nordisk, Principal Investigator, Mercodia, Nestle, Amneal Pharmaceutical, Lifescan Provide Supplies for NIH funded studies. Nothing to Disclose: RG, JL, BME

*Please take note of The Endocrine Society's News Embargo Policy at https://www.endocrine.org/news-room/endo-annual-meeting

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