Saxagliptin and Cardiovascular Outcomes in Patients With Type 2 Diabetes and Moderate or Severe Renal Impairment: Observations From the SAVOR-TIMI 53 Trial

Diabetes Care. 2015 Apr;38(4):696-705. doi: 10.2337/dc14-1850. Epub 2014 Dec 31.

Abstract

Objective: The glycemic management of patients with type 2 diabetes mellitus (T2DM) and renal impairment is challenging, with few treatment 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 m(2); n = 13,916), moderate renal impairment (eGFR 30-50 mL/min/1.73 m(2); n = 2,240), or severe renal impairment (eGFR <30 mL/min/1.73 m(2); 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/1.73 m(2) (HR 1.23 [95% CI 0.99-1.55]), eGFR 30-50 mL/min/1.73 m(2) (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.

Trial registration: ClinicalTrials.gov NCT01107886.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adamantane / analogs & derivatives*
  • Adamantane / therapeutic use
  • Aged
  • Cardiovascular Diseases / diagnosis
  • Cardiovascular Diseases / epidemiology*
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / diagnosis
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / epidemiology*
  • Diabetic Nephropathies / drug therapy*
  • Diabetic Nephropathies / epidemiology
  • Dipeptides / therapeutic use*
  • Female
  • Heart Failure / complications
  • Heart Failure / epidemiology
  • Hospitalization / statistics & numerical data
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Myocardial Infarction / complications
  • Myocardial Infarction / epidemiology
  • Renal Insufficiency / drug therapy*
  • Renal Insufficiency / epidemiology
  • Renal Insufficiency / etiology
  • Severity of Illness Index
  • Stroke / complications
  • Stroke / epidemiology
  • Treatment Outcome

Substances

  • Dipeptides
  • saxagliptin
  • Adamantane

Associated data

  • ClinicalTrials.gov/NCT01107886