1. Thank you for your interest in INVOKANA® (canagliflozin)
Thank you for your interest in INVOKANA® (canagliflozin). The above information is presented in response to your inquiry. This information is taken from the references cited, but is not intended to serve as a substitute for review of these references. This information is not intended to advocate the use of our product in any manner other than as described in the product monograph. Please refer to the INVOKANA® Product Monograph available at for full prescribing information. For additional information, please see the accompanying full scientific summary.
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2. The Canagliflozin and Renal Endpoints in
Study Description
Study Design
Baseline Characteristics
Efficacy Outcomes
Safety Outcomes
SUMMARY
RESOURCES
DISCLAIMER
The Canagliflozin and Renal Endpoints in
Diabetes with Established Nephropathy Clinical
Evaluation (CREDENCE)
CREDENCE (Canagliflozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation), was a phase 3, randomized, double-blind, placebo-controlled, parallel group multicenter clinical trial assessing whether canagliflozin 100 mg has a renal and/or cardiovascular protective effect compared to placebo in patients with type 2 diabetes mellitus (T2DM), Stage 2 or 3 chronic kidney disease (CKD) and macroalbuminuria, who are receiving standard of care.1,2
Perkovic V, Jardine MJ, Neal B, et al. Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy [published online ahead of print April ]. NEJM doi: /NEJMoa
Jardine MJ, Mahaffey KW, Neal B, et al. The Canagliflozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) study rationale, design, and baseline characteristics. Am J Nephrol. 2017;46(6):

3. Baseline Characteristics
Study Description
Study Design
Baseline Characteristics
Efficacy Outcomes
Safety Outcomes
SUMMARY
RESOURCES
DISCLAIMER
Study Design & Methods
Inclusion Criteria
Exclusion Criteria
Efficacy Endpoints
Safety Outcomes
Study Timeline
STUDY DESIGN AND METHODS
Phase 3, randomized, double-blind, placebo-controlled parallel group, multicenter, event driven trial.
Conducted across 690 sites in 34 countries, with 4,401 participants.
Patients randomly assigned to either canagliflozin 100 mg or matching placebo in a 1:1 ratio.
The study consisted of a screening and run-in period, a double-blind treatment period (canagliflozin 100 mg vs. placebo), and a 30-day post treatment (after study completion or permanent discontinuation of study drug) follow-up.
Total duration of the study was planned to be approximately 5.5 years.
Placebo
Canagliflozin 100 mg
Double-blind randomization
(1:1)
Follow-up at Weeks 3, 13, and 26 (face-to-face) then every 13 weeks (alternating phone/face-to-face)
2-week placebo run-in R
Participants continued treatment if eGFR was <30 mL/min/1.73 m2 until chronic dialysis was initiated or kidney transplant occurred.
Jardine MJ, Mahaffey KW, Neal B, et al. The Canagliflozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) study rationale, design, and baseline characteristics. Am J Nephrol. 2017;46(6):

4. Baseline Characteristics
Study Description
Study Design
Baseline Characteristics
Efficacy Outcomes
Safety Outcomes
SUMMARY
RESOURCES
DISCLAIMER
Study Design & Methods
Inclusion Criteria
Exclusion Criteria
Efficacy Endpoints
Safety Outcomes
Study Timeline
KEY INCLUSION CRITERIA
≥30 years of age with T2DM (HbA1c ≥6.5% to ≤12.0%)
Estimated glomerular filtration rate (eGFR) ≥30 to <90 mL/min/1.73m2 and albuminuria (urine albumin:creatinine ratio [UACR] >300 mg/g and ≤5000 mg/g [33.9–565.6 mg/mmol])*
On a stable maximum tolerated or labeled daily dose of an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin II receptor blocker (ARB) for at least 4 weeks prior to randomization
* In order to ensure that the study was able to assess the impact of canagliflozin on the progression of CKD, the intent was that approximately 60% of the patient population have stage 3 CKD (rather than stage 2 CKD), with an eGFR of ≥30 to <60 mL/min/1.73 m2 at study entry.
Jardine MJ, Mahaffey KW, Neal B, et al. The Canagliflozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) study rationale, design, and baseline characteristics. Am J Nephrol. 2017;46(6):

5. Baseline Characteristics
Study Description
Study Design
Baseline Characteristics
Efficacy Outcomes
Safety Outcomes
SUMMARY
RESOURCES
DISCLAIMER
Study Design & Methods
Inclusion Criteria
Exclusion Criteria
Efficacy Endpoints
Safety Outcomes
Study Timeline
KEY EXCLUSION CRITERIA
Nondiabetic kidney disease with a history of treatment of kidney disease with immunosuppression
A history of treatment with dialysis or kidney transplantation
A history of CV events within the previous 12 weeks or a history of New York Heart Association class IV heart failure at any time
Combination use of an ACEi and ARB
Use of direct renin-inhibitor or mineralocorticoid receptor antagonist (MRA)
Concomitant use of an SGLT2 inhibitor within 12 weeks of randomization, current or past participation in another canagliflozin study
Perkovic V, Jardine MJ, Neal B, et al. Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy: Supplementary Appendix [published online ahead of print April ]. NEJM Published 14 April doi: /NEJMoa

6. Baseline Characteristics
Study Description
Study Design
Baseline Characteristics
Efficacy Outcomes
Safety Outcomes
SUMMARY
RESOURCES
DISCLAIMER
Study Design & Methods
Inclusion Criteria
Exclusion Criteria
Efficacy Endpoints
Safety Outcomes
Study Timeline
EFFICACY ENDPOINTS
Primary endpoint:
Composite of end stage kidney disease (ESKD), doubling of serum creatinine, and renal or cardiovascular death (non-dialyzed)
Secondary endpoints:
Composite of cardiovascular death and hospitalization for heart failure
Major cardiovascular events (3-point MACE: CV death, MI, or stroke)
Hospitalization for heart failure
ESKD, doubling of serum creatinine, or renal death
CV death
All-cause mortality
CV death, MI, stroke, hospitalization for heart failure, or hospitalization for unstable angina
Prespecified exploratory endpoints:
Composite endpoint of ESKD and renal or cardiovascular death
Individual components of the composite endpoints
ESKD
Doubling of serum creatinine
Renal death
Cardiovascular death
Fatal and nonfatal MI
Fatal and nonfatal stroke
Hospitalized congestive heart failure
Hospitalized unstable angina
Change in eGFR over time
Change in albuminuria over time
Jardine MJ, Mahaffey KW, Neal B, et al. The Canagliflozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) study rationale, design, and baseline characteristics. Am J Nephrol. 2017;46(6):

7. Baseline Characteristics
Study Description
Study Design
Baseline Characteristics
Efficacy Outcomes
Safety Outcomes
SUMMARY
RESOURCES
DISCLAIMER
Study Design & Methods
Inclusion Criteria
Exclusion Criteria
Efficacy Endpoints
Safety Outcomes
Study Timeline
SAFETY EVALUATIONS AND OUTCOMES
Adverse events: All adverse events were collected and coded using the MedDRA from randomization until 30 days after the last date of blinded study medication
Adverse events of interest: All malignancies, fatal pancreatitis, hemorrhagic/necrotising pancreatitis, severe hypersensitivity reactions (e.g., angioedema, anaphylaxis, Stevens-Johnson syndrome), photosensitivity reactions, serious adverse events of hepatic injury, nephrotoxicity/acute kidney injury, venous thromboembolic events, fractures, diabetic ketoacidosis (and related adverse events including ketoacidosis, metabolic acidosis, or acidosis), amputation, and pregnancy
Hypoglycemia: All episodes of hypoglycemia (both symptomatic and asymptomatic) were recorded on a dedicated hypoglycemia eCRF
Safety laboratory tests: Chemistry, hematology, urinalysis
Physical examination: Pulse, BP, weight
Perkovic V, Jardine MJ, Neal B, et al. Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy: Supplementary Appendix [published online ahead of print April ]. NEJM Published 14 April doi: /NEJMoa

8. Baseline Characteristics
Study Description
Study Design
Baseline Characteristics
Efficacy Outcomes
Safety Outcomes
SUMMARY
RESOURCES
DISCLAIMER
Study Design & Methods
Inclusion Criteria
Exclusion Criteria
Efficacy Endpoints
Safety Outcomes
Study Timeline
STUDY TIMELINE
In July 2018, after the planned interim analysis, The Independent Data Monitoring Committee (IDMC) made the recommendation to stop the CREDENCE trial based on demonstration of efficacy
Interim analysis
2014
2015
2016
2017
2018
2019
First participant enrolled
Last participant randomized
Protocol amendment for lower extremity foot care
Study concluded

9. DEMOGRAPHICS AND DISEASE HISTORY
Study Description
Study Design
Baseline Characteristics
Efficacy Outcomes
Safety Outcomes
SUMMARY
RESOURCES
DISCLAIMER
DEMOGRAPHICS AND DISEASE HISTORY
BASELINE THERAPIES
BASELINE RISK FACTORS
BASELINE RENAL CHARACTERISTICS
DEMOGRAPHICS AND DISEASE HISTORY
Canagliflozin
(n = 2202)
Placebo
(n = 2199)
Total
(N = 4401)
Mean age, years 63
Female, % 35 33 34
Mean duration of diabetes, years 16
Hypertension, % 97
Heart failure (NYHA I-III), % 15
CV disease, % 51 50
Prior amputation, % 5
Race, %
White 68 66 67
Asian 19 21 20
Black or African American
Other 8 9
Geographic region, %
North America 26 28 27
Central/South America 22
Europe
Rest of world 32
Perkovic V, Jardine MJ, Neal B, et al. Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy: Supplementary Appendix [published online ahead of print April ]. NEJM Published 14 April doi: /NEJMoa

10. Study Description
Study Design
Baseline Characteristics
Efficacy Outcomes
Safety Outcomes
SUMMARY
RESOURCES
DISCLAIMER
DEMOGRAPHICS AND DISEASE HISTORY
BASELINE THERAPIES
BASELINE RISK FACTORS
BASELINE RENAL CHARACTERISTICS
BASELINE THERAPIES
Canagliflozin
(n = 2202)
Placebo
(n = 2199)
Total
(N = 4401)
Glucose-lowering agents, %
Insulin 66 65
Metformin 58
Sulfonylurea 28 30 29
DPP-4 inhibitor 17
GLP-1 receptor agonist 4
Renal and CV protective agents, %
RAAS inhibitor
>99.9
99.8
99.9
Statin 70 68 69
Antithrombotic 61 60
Beta blocker 40
Diuretic 47
All patients were required to be receiving a stable dose of an angiotensin-converting–enzyme inhibitor or angiotensin-receptor blocker for at least 4 weeks before randomization
Perkovic V, Jardine MJ, Neal B, et al. Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy: Supplementary Appendix [published online ahead of print April ]. NEJM Published 14 April doi: /NEJMoa

11. BASELINE RISK FACTORS Study Description Study Design Efficacy Outcomes
Baseline Characteristics
Efficacy Outcomes
Safety Outcomes
SUMMARY
RESOURCES
DISCLAIMER
DEMOGRAPHICS AND DISEASE HISTORY
BASELINE THERAPIES
BASELINE RISK FACTORS
BASELINE RENAL CHARACTERISTICS
BASELINE RISK FACTORS
Canagliflozin
(n = 2202)
Placebo
(n = 2199)
Total
(N = 4401)
HbA1c, %
8.3
BMI, kg/m2
31.4
31.3
Systolic BP, mmHg
140
Diastolic BP, mmHg 78
Total cholesterol, mmol/L
4.7
4.6
HDL-C, mmol/L
1.2
LDL-C, mmol/L
2.5
Triglycerides, mmol/L
2.2
Perkovic V, Jardine MJ, Neal B, et al. Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy: Supplementary Appendix [published online ahead of print April ]. NEJM Published 14 April doi: /NEJMoa

12. BASELINE RENAL CHARACTERISTICS
Study Description
Study Design
Baseline Characteristics
Efficacy Outcomes
Safety Outcomes
SUMMARY
RESOURCES
DISCLAIMER
DEMOGRAPHICS AND DISEASE HISTORY
BASELINE THERAPIES
BASELINE RISK FACTORS
BASELINE RENAL CHARACTERISTICS
BASELINE RENAL CHARACTERISTICS
Canagliflozin
(n = 2202)
Placebo
(n = 2199)
Total
(N = 4401)
Mean eGFR, mL/min/1.73 m² 56
eGFR ≥90, % 5
eGFR ≥60 to <90, % 36 35
eGFR ≥45 to <60, % 29
eGFR ≥30 to <45, % 27
eGFR <30, % 4
Median UACR (interquartile range), mg/g
923
( )
931
( )
927
( )
UACR <30, %
<1
UACR , % 11
UACR >300-≤3000, % 77 76
UACR >3000, % 12
Perkovic V, Jardine MJ, Neal B, et al. Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy: Supplementary Appendix [published online ahead of print April ]. NEJM Published 14 April doi: /NEJMoa

13. Baseline Characteristics
Study Description
Study Design
Baseline Characteristics
Efficacy Outcomes
Safety Outcomes
SUMMARY
RESOURCES
DISCLAIMER
PRIMARY OUTCOME
SECONDARY OUTCOMES
EXPLORATORY OUTCOMES
EFFECT ON eGFR
ESKD
MACE
PRIMARY OUTCOME
HHF
Composite outcome: End Stage Kidney Disease (ESKD), Doubling of Serum Creatinine, or Renal or CV Death
Canagliflozin reduced the risk of the primary outcome by 30% (P = )
NNT = 22 over 2.5 years
Adapted from Perkovic V, Jardine MJ, Neal B, et al. Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy [published online ahead of print April ]. NEJM doi: /NEJMoa

14. END STAGE KIDNEY DISEASE (ESKD)
Study Description
Study Design
Baseline Characteristics
Efficacy Outcomes
Safety Outcomes
SUMMARY
RESOURCES
DISCLAIMER
PRIMARY OUTCOME
SECONDARY OUTCOMES
EXPLORATORY OUTCOMES
EFFECT ON eGFR
ESKD
MACE
END STAGE KIDNEY DISEASE (ESKD)
HHF
Component of the Primary Composite Outcome
ESKD: defined as dialysis, renal transplantation, or sustained eGFR <15 mL/min/1.73m2
Canagliflozin reduced the risk of ESKD by 32% (P = 0.002)
NNT = 43 over 2.5 years
Adapted from Perkovic V, Jardine MJ, Neal B, et al. Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy [published online ahead of print April ]. NEJM doi: /NEJMoa

15. Baseline Characteristics
Study Description
Study Design
Baseline Characteristics
Efficacy Outcomes
Safety Outcomes
SUMMARY
RESOURCES
DISCLAIMER
PRIMARY OUTCOME
SECONDARY OUTCOMES
EXPLORATORY OUTCOMES
EFFECT ON eGFR
ESKD
MACE
SECONDARY OUTCOMES
HHF
Outcome
Hazard ratio (95% CI)
P value
Significance
CV death or hospitalization for heart failure
0.69 (0.57–0.83)
<0.001 ✔
CV death, MI, or stroke
0.80 (0.67–0.95)
0.01
Hospitalization for heart failure
0.61 (0.47–0.80)
ESKD, doubling of serum creatinine, or renal death
0.66 (0.53–0.81)
CV death
0.78 (0.61–1.00)
0.0502
Not significant
All-cause mortality
0.83 (0.68–1.02) –
Not formally tested*
CV death, MI, stroke, hospitalization for heart failure, or
hospitalization for unstable angina
0.74 (0.63–0.86)
Patients in the canagliflozin group had a lower risk of several secondary outcomes tested in a hierarchical fashion
*Prespecified secondary outcomes were tested hierarchically. Statistical significance was required before testing the next hypothesis in the hierarchical test procedure in the order listed above.
Perkovic V, Jardine MJ, Neal B, et al. Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy [published online ahead of print April ]. NEJM doi: /NEJMoa
Jardine MJ, Mahaffey KW, Neal B, et al. The Canagliflozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) study rationale, design, and baseline characteristics. Am J Nephrol. 2017;46(6):

16. Baseline Characteristics
Study Description
Study Design
Baseline Characteristics
Efficacy Outcomes
Safety Outcomes
SUMMARY
RESOURCES
DISCLAIMER
PRIMARY OUTCOME
SECONDARY OUTCOMES
EXPLORATORY OUTCOMES
EFFECT ON eGFR
ESKD
MACE
MAJOR ADVERSE CARDIOVASCULAR EVENTS (MACE)
HHF
MACE: defined as composite of cardiovascular death, myocardial infarction (MI), or stroke
Canagliflozin reduced the risk of the composite of cardiovascular death, MI, or stroke by 20% (P = 0.01)
NNT = 40 over 2.5 years
Adapted from Perkovic V, Jardine MJ, Neal B, et al. Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy [published online ahead of print April ]. NEJM doi: /NEJMoa Wheeler DC, Bakris G, Jardine MJ, et al. CREDENCE (Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation). Symposium presented at the ISN World Congress of Nephrology (WCN); 15 April 2019; Melbourne, Australia.

17. HOSPITALIZATION FOR HEART FAILURE (HHF)
Study Description
Study Design
Baseline Characteristics
Efficacy Outcomes
Safety Outcomes
SUMMARY
RESOURCES
DISCLAIMER
PRIMARY OUTCOME
SECONDARY OUTCOMES
EXPLORATORY OUTCOMES
EFFECT ON eGFR
ESKD
MACE
HOSPITALIZATION FOR HEART FAILURE (HHF)
HHF
Canagliflozin reduced the risk of HHF by 39% (P <0.001)
NNT = 46 over 2.5 years
Adapted from Perkovic V, Jardine MJ, Neal B, et al. Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy [published online ahead of print April ]. NEJM doi: /NEJMoa Wheeler DC, Bakris G, Jardine MJ, et al. CREDENCE (Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation). Symposium presented at the ISN World Congress of Nephrology (WCN); 15 April 2019; Melbourne, Australia.

18. Baseline Characteristics
Study Description
Study Design
Baseline Characteristics
Efficacy Outcomes
Safety Outcomes
SUMMARY
RESOURCES
DISCLAIMER
PRIMARY OUTCOME
SECONDARY OUTCOMES
EXPLORATORY OUTCOMES
EFFECT ON eGFR
ESKD
MACE
EXPLORATORY OUTCOMES
HHF
Outcome
Canagliflozin
Placebo
Hazard ratio (95% CI)
P Value
no./total no.
events/1000 patient-yr
ESKD
116/2202
165/2199
20.4
29.4
0.68 (0.54–0.86)
0.002
Doubling of serum creatinine
118/2202
188/2199
20.7
33.8
0.60 (0.48–0.76)
<0.001
Renal death
2/2202
5/2199
0.3
0.9 NA
Cardiovascular death
110/2202
140/2199
19.0
24.4
0.78 (0.61–1.00)
0.05
ESKD and renal or cardiovascular death†
214/2202
287/2199
37.6
51.2
0.73 (0.61–0.87)
Hospitalization for heart failure
89/2202
141/2199
15.7
25.3
0.61 (0.47–0.80)
NA – hazard ratios and 95% confidence intervals (CI) are reported only for outcomes with more than 10 events.
† This outcome was exploratory.
The effects of canagliflozin were also consistent across several renal and cardiovascular exploratory outcomes
Perkovic V, Jardine MJ, Neal B, et al. Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy: Supplementary Appendix [published online ahead of print April ]. NEJM Published 14 April doi: /NEJMoa

19. Baseline Characteristics
Study Description
Study Design
Baseline Characteristics
Efficacy Outcomes
Safety Outcomes
SUMMARY
RESOURCES
DISCLAIMER
PRIMARY OUTCOME
SECONDARY OUTCOMES
EXPLORATORY OUTCOMES
EFFECT ON eGFR
ESKD
MACE
INTERMEDIATE RENAL OUTCOME
HHF
Effect on Estimated GFR
–0.55
Patients treated with canagliflozin had a greater acute reduction in eGFR, but a slower decline in eGFR thereafter compared to placebo. Canagliflozin attenuated the slope of chronic eGFR decline by 2.7 mL/min/1.73 m2/year
–3.72
Acute eGFR slope (3 weeks)
Difference: –3.17 (95% CI, –3.87, –2.47)
Adapted from Perkovic V, Jardine MJ, Neal B, et al. Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy [published online ahead of print April ]. NEJM doi: /NEJMoa

20. Baseline Characteristics
Study Description
Study Design
Baseline Characteristics
Efficacy Outcomes
Safety Outcomes
SUMMARY
RESOURCES
DISCLAIMER
SAFETY OUTCOMES
Outcome
Canagliflozin
Placebo
Hazard ratio (95% CI)
no./total no.
events/1000 patient-yr
Any adverse events
1784/2200
1860/2197
351.4
379.3
0.87 (0.82–0.93)
Any serious adverse event
737/2200
806/2197
145.2
164.4
0.87 (0.79–0.97)
Serious adverse event related to trial drug
62/2200
42/2197
12.2
8.6
1.45 (0.98–2.14)
Amputation
70/2200
63/2197
12.3
11.2
1.11 (0.79–1.56)
Fracture
67/2200
68/2197
11.8
12.1
0.98 (0.70–1.37)
Cancer
Renal-cell carcinoma
1/2200
5/2197
0.2
0.9 NA
Breast cancer
8/761
3/731
4.1
1.6
2.59 (0.69–9.76)
Bladder cancer
10/2200
9/2197
1.7
1.10 (0.45–2.72)
Acute pancreatitis
5/2200
2/2197
1.0
0.4
Hyperkalemia
151/2200
181/2197
29.7
36.9
0.80 (0.65–1.00)
Acute kidney injury
86/2200
98/2197
16.9
20.0
0.85 (0.64–1.13)
Diabetic ketoacidosis
11/2200
1/2197
2.2
10.80 (1.39–83.65)
The overall rates of AEs and serious AEs were similar between the treatment groups.
No difference in risk was observed with canagliflozin compared with placebo for fractures or amputations.
Renal-related AEs were lower in the canagliflozin group compared with placebo.
NA – hazard ratios and 95% confidence intervals (CI) are reported only for outcomes with more than 10 events.
Adapted from Perkovic V, Jardine MJ, Neal B, et al. Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy [published online ahead of print April ]. NEJM doi: /NEJMoa

21. Baseline Characteristics
Study Description
Study Design
Baseline Characteristics
Efficacy Outcomes
Safety Outcomes
SUMMARY
RESOURCES
DISCLAIMER
SUMMARY
Canagliflozin reduced the risk of the primary outcome of ESKD, doubling of serum creatinine, or renal or CV death by 30% (P = ), NNT = 22 over 2.5 years
The results were consistent across a broad range of prespecified subgroups
Canagliflozin reduced the risk of the secondary outcome of ESKD, doubling of serum creatinine, or renal death by 34% (P <0.001), NNT = 28 over 2.5 years
Canagliflozin reduced the risk of major adverse cardiovascular events (CV death, MI, and stroke) by 20% (P = 0.01), NNT = 40 over 2.5 years
Similar risk reductions were seen for exploratory outcomes assessing components of the primary outcome
ESKD: 32% lower, NNT = 43 over 2.5 years
Dialysis, transplantation, or renal death: 28% lower
Canagliflozin reduced the risk of hospitalization for heart failure by 39% (P <0.001), NNT = 46 over 2.5 years
Canagliflozin attenuated the slope of chronic eGFR decline by 2.7 mL/min/1.73 m2/year (-1.9 vs -4.6)
The overall rates of AEs and serious AEs were similar between the treatment groups
No difference in risk was observed with canagliflozin compared with placebo for:
Fracture
Amputation
Perkovic V, Jardine MJ, Neal B, et al. Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy [published online ahead of print April ]. NEJM doi: /NEJMoa

22. Baseline Characteristics
Study Description
Study Design
Baseline Characteristics
Efficacy Outcomes
Safety Outcomes
SUMMARY
RESOURCES
DISCLAIMER
RESOURCES
New England Journal of Medicine CREDENCE Publication:
CREDENCE Presentation Slides:
International Society of Nephrology (ISN) World Congress of Nephrology (WCN) 2019 Webcast:
REFERENCE LIST
Perkovic V, Jardine MJ, Neal B, et al. Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy [published online ahead of print April ]. NEJM doi: /NEJMoa
Perkovic V, Jardine MJ, Neal B, et al. Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy: Supplementary Appendix [published online ahead of print April ]. NEJM Published 14 April doi: /NEJMoa
Jardine MJ, Mahaffey KW, Neal B, et al. The Canagliflozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) study rationale, design, and baseline characteristics. Am J Nephrol. 2017;46(6):
Wheeler DC, Bakris G, Jardine MJ, et al. CREDENCE (Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation). Symposium presented at the ISN World Congress of Nephrology (WCN); 15 April 2019; Melbourne, Australia.

23. Baseline Characteristics
Study Description
Study Design
Baseline Characteristics
Efficacy Outcomes
Safety Outcomes
SUMMARY
RESOURCES
DISCLAIMER
Thank you for your interest in INVOKANA® (canagliflozin). The above information is presented in response to your inquiry. This information is taken from the references cited, but is not intended to serve as a substitute for review of these references. This information is not intended to advocate the use of our product in any manner other than as described in the Product Monograph. Please refer to the INVOKANA® Product Monograph available at for full prescribing information. For additional information, please see the accompanying full scientific summary.
For any questions, please contact Janssen Medical Information at: or