Cardiovascular and renal benefits of dapagliflozin in patients with short and long-standing type 2 diabetes: Analysis from the DECLARE-TIMI 58 trial

Harpreet S. Bajaj, Itamar Raz, Ofri Mosenzon, Sabina A. Murphy, Aliza Rozenberg, Ilan Yanuv, Deepak L. Bhatt, Lawrence A. Leiter, Darren K. McGuire, John P.H. Wilding, Ingrid A.M. Gause-Nilsson, Marc S. Sabatine, Stephen D. Wiviott, Avivit Cahn

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

Aim: To investigate whether the cardiovascular and renal benefits observed with dapagliflozin in the DECLARE-TIMI 58 trial are also observed in patients with short and long-standing diabetes. Materials and Methods: This post hoc analysis studied the dual primary efficacy endpoints, a composite of cardiovascular death or hospitalization for heart failure (CVD/HHF) and major adverse cardiovascular events (MACE; CVD, myocardial infarction [MI], ischaemic stroke) by diabetes duration. Results: Of the 17 160 patients, 3836 had diabetes duration of ≤5 years, 4731 >5-10 years, 3952 >10-15 years, 2433 >15-20 years and 2206 >20 years. Dapagliflozin reduced the risk of CVD/HHF by a similar amount across diabetes duration subgroups, ranging from HR 0.79 (0.58-1.06) in patients with diabetes duration of ≤5 years to 0.75 (0.55-1.03) in those patients with diabetes duration of >20 years (interaction trend P-value 0.76). Hazard ratios (HRs) for MACE ranged from 1.08 (0.87-1.35) in patients with diabetes duration of ≤5 years to 0.67 (0.52-0.86) in those patients with diabetes duration of >20 years (interaction trend P-value 0.004). This was driven by greater reductions in the risk of MI and ischaemic stroke with dapagliflozin in patients with long-standing diabetes (interaction trend P-values 0.019 and 0.015, respectively). The duration-based MACE heterogeneity was apparent in those with or without a history of prior MI and in those with multiple risk factors. The renal-specific outcome was reduced with dapagliflozin with HRs ranging from 0.79 (0.47-1.34) in patients with diabetes duration of ≤5 years to 0.42 (0.25-0.72) in those patients with diabetes duration of >20 years (interaction trend P-value 0.084). Conclusions: Dapagliflozin reduced the risk of CVD/HHF consistently, regardless of diabetes duration, whereas the treatment effect for MACE differed by duration subgroups, with significant reductions with dapagliflozin in patients with long-standing diabetes.

Original languageEnglish (US)
Pages (from-to)1122-1131
Number of pages10
JournalDiabetes, Obesity and Metabolism
Volume22
Issue number7
DOIs
StatePublished - Jul 1 2020

Keywords

  • cardiovascular disease, dapagliflozin, diabetes duration, major adverse cardiovascular events, sodium-glucose co-transporter-2 inhibitors, type 2 diabetes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Fingerprint Dive into the research topics of 'Cardiovascular and renal benefits of dapagliflozin in patients with short and long-standing type 2 diabetes: Analysis from the DECLARE-TIMI 58 trial'. Together they form a unique fingerprint.

  • Cite this

    Bajaj, H. S., Raz, I., Mosenzon, O., Murphy, S. A., Rozenberg, A., Yanuv, I., Bhatt, D. L., Leiter, L. A., McGuire, D. K., Wilding, J. P. H., Gause-Nilsson, I. A. M., Sabatine, M. S., Wiviott, S. D., & Cahn, A. (2020). Cardiovascular and renal benefits of dapagliflozin in patients with short and long-standing type 2 diabetes: Analysis from the DECLARE-TIMI 58 trial. Diabetes, Obesity and Metabolism, 22(7), 1122-1131. https://doi.org/10.1111/dom.14011