a demonstrated safety and tolerability profile across trials may help set expectations1-5

See adverse events across trials

similar overall tolerability profile and similar incidence of hypoglycemia with INVOKANA® 300 mg vs Januvia® 100 mg over 52 weeks1,2

In patients inadequately controlled on metformin + a sulfonylurea

Overall safety and select adverse events and discontinuation rates with INVOKANA® vs Januvia® over 52 weeks1-3

 

Januvia® 100 mg + metformin and a sulfonylurea (n=378)

INVOKANA® 300 mg + metformin and a sulfonylurea (n=377)

 

Overall Incidence

Discontinuation Rate

Overall Incidence

Discontinuation Rate

Any adverse event (AE)

77.5%

2.9%

76.7%

5.3%

AEs related to study drug*

27.8%

1.6%

34.0%

3.2%

Serious AEs related to study drug*

0%

0%

0.3%

0.3%

Urinary tract infection

5.6%

0%

4.0%

0.3%

Hypoglycemia

40.7%

0%

43.2%

0.3%

Genital mycotic infection

 

 

 

 

Male

0.5%

0%

9.2%

0.3%

Female

4.3%

0%

15.3%

0%

Osmotic diuresis–related AEs

 

 

 

 

Increased urine frequency

1.3%

0%

1.6%

0.3%

Increased urine volume

0%

0%

0.8%

0.3%

Volume-related AEs

 

 

 

 

Postural dizziness

0.5%

0.3%

0%

0%

Orthostatic hypotension

0.3%

0%

0%

0%

The recommended starting dose of INVOKANA® is 100 mg once daily.1

*Possibly, probably, or very likely related to study drug, as assessed by investigators.

Januvia® 100 mg, n=215; INVOKANA® 300 mg, n=207; including balanitis, balanitis Candida, balanoposthitis, genital candidiasis, and genital infection fungal.

Januvia® 100 mg, n=163; INVOKANA® 300 mg, n=170; including vaginal infection, vulvovaginal candidiasis, vulvovaginal mycotic infection, and vulvovaginitis.

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similar overall incidence of adverse events and significantly lower incidence of hypoglycemia* with INVOKANA® vs glimepiride over 52 weeks1,4

In patients inadequately controlled on metformin

Overall safety and select adverse events with INVOKANA® vs glimepiride over 52 weeks1,3,4

 

Glimepiride + metformin (n=482)

INVOKANA® 100 mg + metformin (n=483)

INVOKANA® 300 mg + metformin (n=485)

 

 

 

 

Any adverse event (AE)

69%

64%

69%

AEs leading to discontinuation

6%

5%

7%

AEs related to study drug

23%

24%

30%

Serious AEs related to study drug

0%

0.4%

0%

Urinary tract infection§

5%

6%

6%

Hypoglycemia

34.2%

5.6%

4.9%

Genital mycotic infection

 

 

 

Male||

1%

7%

8%

Female

2%

11%

14%

Osmotic diuresis–related AEs

 

 

 

Increased urine frequency

<1%

3%

3%

Increased urine volume

<1%

<1%

<1%

Volume-related AEs

 

 

 

Postural dizziness

<1%

<1%

<1%

Orthostatic hypotension

0%

<1%

<1%

All AEs are reported irrespective of rescue drug, except for osmotic diuresis–related and volume-related events, which are reported before the start of rescue therapy.

*Prespecified secondary endpoint.

Glimepiride titration up to 6 mg or 8 mg was allowed throughout the study.

Possibly, probably, or very likely related to study drug, as assessed by investigators.

§Including cystitis, pyelonephritis chronic, and urinary tract infection.

||Glimepiride, n=263; INVOKANA® 100 mg, n=252; INVOKANA® 300 mg, n=241; including balanitis, balanitis Candida, balanoposthitis, genital candidiasis, and genital infection fungal.

Glimepiride, n=219; INVOKANA® 100 mg, n=231; INVOKANA® 300 mg, n=244; including vaginal infection, vulvitis, vulvovaginal candidiasis, vulvovaginal mycotic infection, and vulvovaginitis.

similar overall incidence of adverse events and incidence of hypoglycemia vs placebo over 26 weeks1,5

In patients inadequately controlled on diet + exercise

Overall safety and select adverse events and discontinuation rates with INVOKANA® vs placebo over 26 weeks1, 3, 5

 

Placebo (n=192)

INVOKANA® 100 mg (n=195)

INVOKANA® 300 mg (n=197)

 

Overall Incidence

Discontinuation Rate

Overall Incidence

Discontinuation Rate

Overall Incidence

Discontinuation Rate

Any adverse event (AE)

52.6%

1.0%

61.0%

3.1%

59.9%

2.0%

AEs related to study drug*

9.4%

0%

17.4%

1.5%

25.4%

2.0%

Serious AEs related to study drug*

0%

0%

1.5%

0.5%

0%

0%

Urinary tract infection

4.2%

0%

7.2%

0%

5.1%

0%

Hypoglycemia

2.6%

0%

3.6%

0%

3.0%

0%

Genital mycotic infection

 

 

 

 

 

 

Male

0%

0%

2.5%

0%

5.6%

0.5%

Female

3.8%

0%

8.8%

0.5%

7.4%

0%

Osmotic diuresis–related AEs

 

 

 

 

 

 

Increased urine frequency

0.5%

0%

2.6%

0%

3.0%

0.5%

Increased urine volume

0%

0%

0%

0%

3.0%

0%

Volume-related AEs

 

 

 

 

 

 

Postural dizziness

0%

0%

0.5%

0%

1.0%

0%

Orthostatic hypotension

0%

0%

0%

0%

1.0%

0%

All AEs are reported for regardless of rescue medication, except for osmotic diuresis–related and volume-related AEs, which are reported for before the start of rescue therapy.

*Possibly, probably, or very likely related to study drug, as assessed by investigators.

Placebo, n=88; INVOKANA® 100 mg, n=81; INVOKANA® 300 mg, n=89; including balanitis, balanitis Candida, balanoposthitis, and genital infection fungal.

Placebo, n=104; INVOKANA® 100 mg, n=114; INVOKANA® 300 mg, n=108; including vaginal infection, vulvitis, vulvovaginal candidiasis, vulvovaginal mycotic infection, and vulvovaginitis.

Triple therapy vs Januvia® + metformin and SU at 52 weeks (Schernthaner et al)

A randomized, double-blind, active-controlled 52-week study of 755 patients with type 2 diabetes who were inadequately controlled on maximum doses of metformin (≥2000 mg/day, or ≥1500 mg/day if higher dose not tolerated) and near maximally or maximally effective doses of a sulfonylurea. Patients received Januvia® (sitagliptin) 100 mg (n=378) once daily or INVOKANA® 300 mg (n=377) once daily, each in combination with metformin + a sulfonylurea. Mean baseline A1C values were, respectively, 8.13% and 8.12%. The primary endpoint was the change in A1C from baseline to week 52. Prespecified secondary endpoints included change in fasting plasma glucose, percent change in body weight, and change in systolic blood pressure. Additional efficacy endpoints included percent of patients with A1C <7.0%.1,2

Dual therapy vs glimepiride + metformin at 52 weeks (Cefalu et al)

The efficacy and safety of INVOKANA® were compared with glimepiride in 1450 patients on stable doses of metformin (≥2000 mg/day, or ≥1500 mg/day if higher dose not tolerated). In this 52-week, double-blind, active-controlled study, patients were randomized to receive glimepiride (titration allowed throughout the 52-week study up to 6 mg or 8 mg [mean daily dose=5.6 mg]) + metformin (n=482), INVOKANA® 100 mg + metformin (n=483), or INVOKANA® 300 mg + metformin (n=485), administered once daily. Mean baseline A1C values were, respectively, 7.83%, 7.78%, and 7.79%. The primary endpoint was the change in A1C from baseline to week 52. Prespecified secondary endpoints included percent change in body weight, change in systolic blood pressure, and the proportion of patients with documented hypoglycemic episodes.1,4

Monotherapy vs placebo + diet and exercise at 26 weeks (Stenlöf et al)

The efficacy and safety of INVOKANA® monotherapy were assessed in subjects with type 2 diabetes mellitus who were inadequately controlled with diet and exercise. In this 26-week, double-blind, placebo-controlled study, 584 patients were randomized to receive placebo (n=192), INVOKANA® 100 mg (n=195), or INVOKANA® 300 mg (n=197). Mean baseline A1C values were, respectively, 7.97%, 8.06%, and 8.01%. The primary endpoint was the change in A1C from baseline to week 26. Prespecified secondary endpoints included change in fasting plasma glucose, change in percent body weight, and change in systolic blood pressure.1,5

References: 1. INVOKANA® [prescribing information]. Titusville, NJ: Janssen Pharmaceuticals, Inc. 2. Schernthaner G, Gross JL, Rosenstock J, et al. Canagliflozin compared with sitagliptin for patients with type 2 diabetes who do not have adequate glycemic control with metformin plus sulfonylurea: a 52-week randomized trial [published correction appears in Diabetes Care. 2013;36(12):4172]. Diabetes Care. 2013;36(9):2508-2515. 3. Data on file. Janssen Pharmaceuticals, Inc., Titusville, NJ. 4. Cefalu WT, Leiter LA, Yoon K-H, et al. Efficacy and safety of canagliflozin versus glimepiride in patients with type 2 diabetes inadequately controlled with metformin (CANTATA-SU): 52 week results from a randomised double-blind, phase 3 non-inferiority trial. Lancet. 2013;382(9896):941-950. 5. Stenlöf K, Cefalu WT, Kim KA, et al. Efficacy and safety of canagliflozin monotherapy in subjects with type 2 diabetes mellitus inadequately controlled with diet and exercise. Diabetes Obes Metab. 2013;15(4):372-382.