- Mean duration of diabetes: 15.8 years
- Mean baseline eGFR: 56.2 mL/min/1.73 m2
- Median baseline urinary albumin-to-creatinine ratio: 927 mg/g
|Adverse event† rate per 100 patient-years over 42 months1|
|Any adverse event (AE)||37.93||35.14||0.87 (0.82, 0.93)|
|Any serious AE||16.44||14.52||0.87 (0.79, 0.97)|
|Serious AEs related to trial drug||0.86||1.22||1.45 (0.98, 2.14)|
|Amputation||1.12||1.23||1.11 (0.79, 1.56)|
|Fracture||1.21||1.18||0.98 (0.70, 1.37)|
|Breast cancer§||0.16||0.41||2.59 (0.69, 9.76)|
|Bladder cancer||0.16||0.17||1.10 (0.45, 2.72)|
|HyperkalemiaII||3.69||2.97||0.80 (0.65, 1.00)|
|Acute kidney injury||2.00||1.69||0.85 (0.64, 1.13)|
|Diabetic ketoacidosis¶||0.02||0.22||10.80 (1.39, 83.65)|
|Male genital mycotic infection||0.09||0.84||9.30 (2.83, 30.60)|
|Female genital mycotic infection||0.61||1.26||2.10 (1.00, 4.45)|
The incidence of hypotension was 2.8% for INVOKANA® and 1.5% for placebo.2
eGFR is measured in mL/min/1.73 m 2.
*With albuminuria >300 mg/day.
†Amputation, fracture, and cancer events were determined in the on-study population, whereas the other safety events were determined in the on-treatment population. The analyses for fracture, renal-cell carcinoma, acute pancreatitis, and diabetic ketoacidosis were based on confirmed and adjudicated results.
‡NA denotes not applicable because hazard ratios and 95% confidence intervals were reported only for outcomes with >10 events.
§The diagnosis of breast cancer was established only in women.
IIAdverse events of hyperkalemia were spontaneously reported by the investigator. The definition of hyperkalemia includes the preferred terms "hyperkalemia" and "blood potassium increased" in the Medical Dictionary for Regulatory Activities.
¶All potential ketone-related events were adjudicated for diabetic ketoacidosis by an independent adjudication committee on the basis of clinical presentation and predefined biochemical measures.
DKD=diabetic kidney disease; T2D=type 2 diabetes.
3.5-year renal outcomes trial
CREDENCE (Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation) was a randomized, double-blind, parallel group, multicenter, event-driven clinical trial. The trial compared the effects of INVOKANA® 100 mg vs placebo in 4401 men and women with type 2 diabetes and diabetic kidney disease (described as chronic kidney disease with eGFR 30 to <90 mL/min/1.73 m2 and albuminuria [ratio of albumin to creatinine >300 to 5000 mg/g]) who were already taking a stable, maximum-tolerated, or labeled dose (for ≥4 weeks prior to randomization) of an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB). The mean eGFR of patients was 56.2 mL/min/1.73 m2 and the median urinary albumin-to-creatinine ratio was 927 mg/g. The primary efficacy outcome was the composite of end-stage kidney disease (dialysis, transplant, or eGFR <15 mL/min/1.73 m2), doubling of serum creatinine, or renal or cardiovascular (CV) death. Prespecified secondary outcomes included a composite of CV death or hospitalization for heart failure; a composite of heart attack, stroke, or CV death; hospitalization for heart failure; and a composite of end-stage kidney disease, doubling of the serum creatinine level, or renal death.1
References: 1. Perkovic V, Jardine MJ, Neal B, et al. Canagliflozin and renal outcomes in type 2 diabetes and nephropathy. N Engl J Med. 2019;380(24):2295-2306. Supplementary appendix available at: doi:10.1056/NEJMoa1811744. 2. INVOKANA® [prescribing information]. Titusville, NJ: Janssen Pharmaceuticals, Inc.