Geographic and racial variability in kidney, cardiovascular and safety outcomes with canagliflozin: A secondary analysis of the CREDENCE randomized trial

Diabetes Obes Metab. 2024 Sep;26(9):3530-3540. doi: 10.1111/dom.15685. Epub 2024 Jun 19.

Abstract

Aim: To explore the effect of canagliflozin on kidney and cardiovascular events and safety outcomes in individuals with type 2 diabetes and chronic kidney disease across geographic regions and racial groups.

Materials and methods: A stratified Cox proportional hazards model was used to assess efficacy and safety outcomes by geographic region and racial group. The primary composite outcome was a composite of end-stage kidney disease (ESKD), doubling of the serum creatinine (SCr) level, or death from kidney or cardiovascular causes. Secondary outcomes included: (i) cardiovascular death or heart failure (HF) hospitalization; (ii) cardiovascular death, myocardial infarction (MI) or stroke; (iii) HF hospitalization; (iv) doubling of the SCr level, ESKD or kidney death; (v) cardiovascular death; (vi) all-cause death; and (vii) cardiovascular death, MI, stroke, or hospitalization for HF or for unstable angina.

Results: The 4401 patients were divided into six geographic region subgroups: North America (n = 1182, 27%), Central and South America (n = 941, 21%), Eastern Europe (n = 947, 21%), Western Europe (n = 421, 10%), Asia (n = 749, 17%) and Other (n = 161, 4%). The analyses included four racial groups: White (n = 2931, 67%), Black or African American (n = 224, 5%), Asian (n = 877, 20%) and Other (n = 369, 8%). Canagliflozin reduced the relative risk of the primary composite outcome in the overall trial by 30% (hazard ratio 0.70, 95% confidence interval 0.59-0.82; P = 0.00001). Across geographic regions and racial groups, canagliflozin consistently reduced the primary composite endpoint without evidence of heterogeneity (interaction P values of 0.39 and 0.91, respectively) or significant safety outcome differences.

Conclusions: Canagliflozin reduces the risk of kidney and cardiovascular events similarly across geographic regions and racial groups.

Keywords: SGLT2 inhibitor; canagliflozin; cardiovascular disease; diabetic nephropathy; heart failure; type 2 diabetes.

Publication types

  • Randomized Controlled Trial
  • Multicenter Study

MeSH terms

  • Aged
  • Canagliflozin* / adverse effects
  • Canagliflozin* / therapeutic use
  • Cardiovascular Diseases* / epidemiology
  • Cardiovascular Diseases* / mortality
  • Cardiovascular Diseases* / prevention & control
  • Diabetes Mellitus, Type 2* / complications
  • Diabetes Mellitus, Type 2* / drug therapy
  • Diabetes Mellitus, Type 2* / ethnology
  • Diabetic Nephropathies
  • Europe / epidemiology
  • Female
  • Hospitalization / statistics & numerical data
  • Humans
  • Kidney Failure, Chronic / complications
  • Kidney Failure, Chronic / ethnology
  • Male
  • Middle Aged
  • North America / epidemiology
  • Proportional Hazards Models
  • Renal Insufficiency, Chronic / complications
  • Renal Insufficiency, Chronic / ethnology
  • Sodium-Glucose Transporter 2 Inhibitors* / adverse effects
  • Sodium-Glucose Transporter 2 Inhibitors* / therapeutic use
  • Treatment Outcome

Substances

  • Canagliflozin
  • Sodium-Glucose Transporter 2 Inhibitors