Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes and moderate or severe renal impairment: Observations from the SAVOR-TIMI 53 trial

SAVOR-TIMI 53 Steering Committee and Investigators

Research output: Contribution to journalArticle

99 Scopus citations

Abstract

OBJECTIVE The glycemic management of patients with type 2 diabetes mellitus (T2DM) and renal impairment is challenging, with fewtreatment options. We investigated the effect of saxagliptin in the Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus (SAVOR)-Thrombolysis in Myocardial Infarction (TIMI) 53 trial according to baseline renal function. RESEARCH DESIGN AND METHODS Patients with T2DM at risk for cardiovascular events were stratified as having normal or mildly impaired renal function (estimated glomerular filtration rate [EGFR] >50 mL/min/1.73 m2; n = 13,916), moderate renal impairment (EGFR 30-50 mL/min/1.73 m2; n = 2,240), or severe renal impairment (EGFR <30 mL/min/1.73 m2; n = 336) and randomized to receive saxagliptin or placebo. The primary end point was cardiovascular death, myocardial infarction, or ischemic stroke. RESULTS After a median duration of 2 years, saxagliptin neither increased nor decreased the risk of the primary and secondary composite end points compared with placebo, irrespective of renal function (all P for interactions ‡0.19). Overall, the risk of hospitalization for heart failure among the three EGFR groups of patients was 2.2% (referent), 7.4% (adjusted hazard ratio [HR] 2.38 [95% CI 1.95-2.91], P < 0.001), and 13.0% (adjusted HR 4.59 [95% CI 3.28-6.28], P < 0.001), respectively. The relative risk of hospitalization for heart failure with saxagliptin was similar (P for interaction = 0.43) in patients with EGFR >50 mL/min/1.73m2 (HR 1.23 [95% CI 0.99-1.55]), EGFR 30-50 mL/min/1.73 m2 (HR 1.46 [95% CI 1.07-2.00]), and in patients with EGFR <30 (HR 0.94 [95% CI 0.52-1.71]). Patients with renal impairment achieved reductions in microalbuminuria with saxagliptin (P = 0.041) that were similar to those of the overall trial population. CONCLUSIONS Saxagliptin did not affect the risk of ischemic cardiovascular events, increased the risk of heart failure hospitalization, and reduced progressive albuminuria, irrespective of baseline renal function.

Original languageEnglish (US)
Pages (from-to)696-705
Number of pages10
JournalDiabetes care
Volume38
Issue number4
DOIs
StatePublished - Apr 2015

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Advanced and Specialized Nursing

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