Dipeptidyl peptidase-4 inhibitor cardiovascular safety in patients with type 2 diabetes, with cardiovascular and renal disease: a retrospective cohort study

Sheriza Baksh,G Caleb Alexander,Jodi B Segal,Hsien-Yen Chang,Omar Mansour,Mara Mcadams-Demarco,Jiajun Wen,Stephan Ehrhardt

doi:10.1038/s41598-021-95687-z

Sheriza Baksh, G Caleb Alexander + Show 6 more

Open Access

https://doi.org/10.1038/s41598-021-95687-z

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Abstract

Clinical trials investigating cardiovascular safety of dipeptidyl peptidase-IV inhibitors (DPP-4i) among patients with cardiovascular and renal disease rarely recruit patients with renal impairment, despite associations with increased risk for major adverse cardiovascular events (MACE). We investigated the risk of MACE associated with the use of DPP-4i among these high-risk patients. Using a new-user, retrospective, cohort design, we analyzed 2010–2015 IBM MarketScan Commercial Claims and Encounters for patients with diabetes, comorbid with cardiovascular disease and/or renal impairment. We compared time to first MACE for DPP-4i versus sulfonylurea and versus metformin. Of 113,296 individuals, 9146 (8.07%) were new DPP-4i users, 17,481 (15.43%) were new sulfonylurea users, and 88,596 (78.20%) were new metformin users. Exposure groups were not mutually exclusive. DPP-4i was associated with lower risk for MACE than sulfonylurea (aHR 0.84; 95% CI 0.74, 0.93) and similar risk for MACE to metformin (aHR 1.07; 95% CI [1.04, 1.16]). DPP-4i use was associated with lower risk for MACE compared to sulfonylureas and similar risk for MACE compared to metformin. This association was most evident in the first year of therapy, suggesting that DPP-4i is a safer choice than sulfonylurea for diabetes treatment initiation in high-risk patients.

Highlights

Clinical trials investigating cardiovascular safety of dipeptidyl peptidase-IV inhibitors (DPP-4i) among patients with cardiovascular and renal disease rarely recruit patients with renal impairment, despite associations with increased risk for major adverse cardiovascular events (MACE)
Results were not sensitive to changes in the latency period after the last dose of exposure for the primary analysis results, nor did they differ substantively when lagging the latency period by 7-days or 30-days (Additional File 1, Supplementary Appendix 4). In this longitudinal study of commercial claims data for individuals with diabetes, having cardiovascular disease and renal impairment, new use of DPP-4i was associated with a lower risk for MACE compared to sulfonylureas, and a comparable risk compared to metformin
New use of DPP-4i was not shown to be associated with the following individual components of MACE: heart failure, stroke, or acute myocardial infarction

Summary

Introduction

Clinical trials investigating cardiovascular safety of dipeptidyl peptidase-IV inhibitors (DPP-4i) among patients with cardiovascular and renal disease rarely recruit patients with renal impairment, despite associations with increased risk for major adverse cardiovascular events (MACE). DPP-4i use was associated with lower risk for MACE compared to sulfonylureas and similar risk for MACE compared to metformin. One important class of medicines to treat type 2 diabetes are the dipeptidyl peptidase-IV inhibitors (DPP4i), which act by slowing the breakdown of glucagon-like peptide-1 (GLP-1), inhibiting glucagon release and increasing insulin r elease[4]. Since they were introduced in 2006, four DPP-4i have been approved by the FDA for stand-alone use or as part of fixed-dose combination products, and they rank third in utilization after metformin and sulfonylurea with 8% of antidiabetic drug p rescriptions[5]. Total patients exposed to DPP-4i, Sulfonylurea, or Metformin with cardiovascular disease and/or renal impairment at baseline (N=113,296)

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