~1 in 3 patients with type 2 diabetes also has diabetic kidney disease (DKD)1,2*As renal function declines, the prevalence of heart failure increases3†

INVOKANA® is the only T2D therapy approved by the FDA to reduce the risk of end-stage kidney disease, doubling of serum creatinine, cardiovascular death, and hospitalization for heart failure in patients who have T2D and diabetic nephropathy with albuminuria 300 mg/day4

Help protect patients who have DKD and T2D

INVOKANA® 100 mg is the only SGLT2i proven to slow the progression of DKD8

INVOKANA® reduced the relative risk of the primary composite outcome of end-stage kidney disease,§ doubling of serum creatinine, and renal or CV death8

The landmark CREDENCE trial ended early after the overall risks and benefits were assessed and clear evidence of efficacy was shown.8

Patients were already taking a maximum tolerated dose of an ACEi or ARB.8

 

eGFR is measured in mL/min/1.73 m2.

With albuminuria 300 mg/day.

§End-stage kidney disease was defined as dialysis for ≥30 days, kidney transplantation, or an eGFR 15 mL/min/1.73 m2 sustained for ≥30 days.

||There were not enough events to evaluate the risk of renal death (placebo, n=5; INVOKANA®, n=2). INVOKANA® is not indicated to reduce the risk of renal death.

 

In patients who had DKD and T2D

INVOKANA® 100 mg reduced the risk of hospitalization for heart failure by 39%

Patients were already taking a maximum tolerated dose of an ACEi or ARB.9

eGFR is measured in mL/min/1.73 m2.

With albuminuria 300 mg/day.

Prespecified secondary endpoint.

#RRR was calculated using the following formula: 100 x (1–HR).

INVOKANA® 100 mg has a proven safety profile in patients with DKD and T2D who have an eGFR as low as 308

  • N=4401

  • 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

  Placebo INVOKANA®
100 mg
Hazard ratio
(95% Cl) 
Adverse event** rate per 100 patient-years over 42 months8
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)
Renal-cell carcinoma 0.09 0.02 NA††
Breast cancer‡‡ 0.16 0.41 2.59 (0.69, 9.76)
Bladder cancer 0.16 0.17 1.10 (0.45, 2.72)
Acute pancreatitis 0.04 0.10 NA††
Hyperkalemia§§ 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)

eGFR is measured in mL/min/1.73 m2.

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.

§§Adverse 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.

‖‖AII potential ketone-related events were adjudicated for diabetic ketoacidosis by an independent adjudication committee on the basis of clinical presentation and predefined biochemical measures.

Indication matters¶¶

Consider the only SGLT2i approved by the FDA for all of the following4-7:

There have been no head-to-head clinical trials comparing the efficacy or safety of SGLT2 inhibitors. No direct evaluation of comparative clinical profiles can be made based on prescribing information of each SGLT2i.

eGFR is measured in mL/min/1.73 m2.

With albuminuria 300 mg/day.

§ESKD was defined as dialysis for ≥30 days, kidney transplantation, or an eGFR 15 mL/min/1.73 m² sustained for ≥30 days.

¶¶Based on the prescribing information of each SGLT2i.

##Patients who have an eGFR 30 mL/min/1.73 m2 and albuminuria 300 mg/day, and who are already taking INVOKANA® 100 mg, can continue on therapy until dialysis.

 

Initiate INVOKANA® 100 mg once daily for patients with DKD and T2D4

  • Patients already on INVOKANA® who have an eGFR 30 and albuminuria 300 mg/day, can continue on 100 mg once daily1

In the CREDENCE trial, patients continued on INVOKANA® 100 mg until initiation of dialysis.1

INVOKANA® is contraindicated in patients with an eGFR 30 who are being treated for glycemic control or are on dialysis.1

eGFR is measured in mL/min/1.73 m2.

With albuminuria 300 mg/day.

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® (canagliflozin) 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 for these analyses 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 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.8

ACEi=angiotensin-converting enzyme inhibitor; ARB=angiotensin receptor blocker; CREDENCE=Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation; CV=cardiovascular; CVD=cardiovascular disease; ESKD=end-stage kidney disease; HR=hazard ratio; RRR=relative risk reduction; SGLT2i=sodium-glucose co-transporter 2 inhibitor; T2D=type 2 diabetes.

References: 1. Bailey RA, Wang Y, Zhu V, Rupnow MF. Chronic kidney disease in US adults with type 2 diabetes: an updated national estimate of prevalence based on Kidney Disease: Improving Global Outcomes (KDIGO) staging. BMC Res Notes. 2014;7:415. 2. What is chronic kidney disease? National Institute of Diabetes and Digestive and Kidney Diseases website. https://www.niddk.nih.gov/health-information/kidney-disease/chronic-kidney-disease-ckd/what-is-chronic-kidney-disease. Accessed September 10, 2019. 3. Cardiovascular disease in patients with CKD. United States Renal Data System website. https://www.usrds.org/2018/download/v1_c04_CKD_CVD_18_usrds.pdf. Accessed September 20, 2019. 4. INVOKANA® [prescribing information]. Titusville, NJ: Janssen Pharmaceuticals, Inc. 5. Jardiance® [prescribing information]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc. 6. Farxiga® [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP. 7. SteglatroTM [prescribing information]. Whitehouse Station, NJ: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. 8. 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. 9. Mahaffey KW, Jardine MJ, Bompoint S, et al. Canagliflozin and cardiovascular and renal outcomes in type 2 diabetes mellitus and chronic kidney disease in primary and secondary cardiovascular prevention groups. Circulation. 2019;140(9):739-750.