Dapagliflozin and Prevention of Kidney Disease Among Patients With Type 2 Diabetes: Post Hoc Analyses From the DECLARE-TIMI 58 Trial

Diabetes Care. 2022 Oct 1;45(10):2350-2359. doi: 10.2337/dc22-0382.


Objective: In patients with moderate to severe albuminuric kidney disease, sodium-glucose cotransporter 2 inhibitors reduce the risk of kidney disease progression. These post hoc analyses assess the effects of dapagliflozin on kidney function decline in patients with type 2 diabetes (T2D), focusing on populations with low kidney risk.

Research design and methods: In the Dapagliflozin Effect on Cardiovascular Events-Thrombolysis in Myocardial Infarction 58 (DECLARE-TIMI 58) trial, patients with T2D at high cardiovascular risk were randomly assigned to dapagliflozin versus placebo. Outcomes were analyzed by treatment arms, overall, and by Kidney Disease: Improving Global Outcomes (KDIGO) risk categories. The prespecified kidney-specific composite outcome was a sustained decline ≥40% in the estimated glomerular filtration rate (eGFR) to <60 mL/min/1.73 m2, end-stage kidney disease, and kidney-related death. Other outcomes included incidence of categorical eGFR decline of different thresholds and chronic (6 month to 4 year) or total (baseline to 4 year) eGFR slopes.

Results: Most participants were in the low-moderate KDIGO risk categories (n = 15,201 [90.3%]). The hazard for the kidney-specific composite outcome was lower with dapagliflozin across all KDIGO risk categories (P-interaction = 0.97), including those at low risk (hazard ratio [HR] 0.54, 95% CI 0.38-0.77). Risks for categorical eGFR reductions (≥57% [in those with baseline eGFR ≥60 mL/min/1.73 m2], ≥50%, ≥40%, and ≥30%) were lower with dapagliflozin (HRs 0.52, 0.57, 0.55, and 0.70, respectively; P < 0.05). Slopes of eGFR decline favored dapagliflozin across KDIGO risk categories, including the low KDIGO risk (between-arm differences of 0.87 [chronic] and 0.55 [total] mL/min/1.73 m2/year; P < 0.0001).

Conclusions: Dapagliflozin mitigated kidney function decline in patients with T2D at high cardiovascular risk, including those with low KDIGO risk, suggesting a role of dapagliflozin in the early prevention of diabetic kidney disease.

Trial registration: ClinicalTrials.gov NCT01730534.

Publication types

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

MeSH terms

  • Benzhydryl Compounds / pharmacology
  • Diabetes Mellitus, Type 2* / complications
  • Diabetes Mellitus, Type 2* / drug therapy
  • Diabetic Nephropathies* / etiology
  • Glomerular Filtration Rate
  • Glucose / pharmacology
  • Glucosides
  • Humans
  • Myocardial Infarction* / complications
  • Sodium
  • Sodium-Glucose Transporter 2 Inhibitors* / adverse effects


  • Benzhydryl Compounds
  • Glucosides
  • Sodium-Glucose Transporter 2 Inhibitors
  • dapagliflozin
  • Sodium
  • Glucose

Associated data

  • ClinicalTrials.gov/NCT01730534
  • figshare/10.2337/figshare.20365530