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Similar overall incidence of adverse events and significantly lower incidence of hypoglycemia with INVOKANA® vs glimepiride over 52 weeks1-3

Overall Safety and Select Adverse Events and Discontinuation Rates With INVOKANA® vs Glimepiride Over 52 Weeks1,2

  Glimepiride* + metformin (n=482) Discontinuation rate: Glimepiride + metformin (n=482) INVOKANA® 100 mg + metformin (n=483) Discontinuation rate: INVOKANA® 100 mg + metformin (n=483) INVOKANA® 300 mg + metformin (n=485) Discontinuation rate: INVOKANA® 300 mg + metformin (n=485)
Any AE
69% 6% 64% 5% 69% 7%
AEs related to study drug 23% 2.5% 24% 3.5% 30% 4.1%
Serious AEs related to study drug 0% 0% 0.4% 0.4% 0% 0%
Urinary tract infection 5% 0% 6% 0.4% 6% 0%
Genital mycotic infection
           
Male§ 1% 0% 7% 0.2% 8% 0.4%
Femaleıı 2% 0% 11% 0.2% 14% 0.4%
           
Increased urine frequency <1% 0% 3% 0.2% 3% 0%
Increased urine volume <1% 0% <1% 0.2% <1% 0.2%
           
Postural dizziness <1% 0.2% <1% 0.2% <1% 0%
Orthostatic hypotension 0% 0% <1% 0% <1% 0%
  Glimepiride* + metformin (n=482) INVOKANA® 100 mg + metformin (n=483) INVOKANA® 300 mg + metformin (n=485)
Any AE
69% 64% 69%
AEs related to study drug 23% 24% 30%
Serious AEs related to study drug 0% 0.4% 0%
Urinary tract infection 5% 6% 6%
Genital mycotic infection
Male§ 1% 7% 8%
Femaleıı 2% 11% 14%
Increased urine frequency <1% 3% 3%
Increased urine volume <1% <1% <1%
Postural dizziness <1% <1% <1%
Orthostatic hypotension 0% <1% <1%
Discontinuation Rates
Any AE 6% 5% 7%
AEs related to study drug 2.5% 3.5% 4.1%
Serious AEs related to study drug 0% 0.4% 0%
Urinary tract infection 0% 0.4% 0%
Genital mycotic infection
Male§ 0% 0.2% 0.4%
Femaleıı 0% 0.2% 0.4%
Osmotic diuresis–related AEs
Increased urine frequency 0% 0.2% 0%
Increased urine volume 0% 0.2% 0.2%
Volume-related AEs
Postural dizziness 0.2% 0.2% 0%
Orthostatic hypotension 0% 0% 0%

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.
*Mean daily dose=5.6 mg. 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.
ııGlimepiride, n=219; INVOKANA® 100 mg, n=231; INVOKANA® 300 mg, n=244; including vaginal infection, vulvitis, vulvovaginal candidiasis, vulvovaginal mycotic infection, and vulvovaginitis.

Secondary Endpoint: Percent of Patients With Documented Hypoglycemia Over 52 Weeks2


Type 2 diabetes patients with documented hypoglycemia: INVOKANA® vs glimepirideType 2 diabetes patients with documented hypoglycemia: INVOKANA® vs glimepiride

P <0.001 vs glimepiride + metformin.
#Mean daily dose=5.6 mg. Glimepiride titration up to 6 mg or 8 mg was allowed throughout the study.
 
 

Similar overall safety and select AEs over 104 weeks4

Overall Incidence of Adverse Events With INVOKANA® vs Glimepiride Over 104 Weeks4

  Glimepiride#
+ metformin (n=482)
INVOKANA® 100 mg + metformin (n=483) INVOKANA® 300 mg + metformin (n=485)
Any AE
78.4% 73.3% 77.9%
AEs leading to discontinuation 7.3% 6.2% 9.5%
AEs related to study drug** 27.8% 28.6% 32.8%
Male genital mycotic infection†† 1.9% 9.5% 9.1%
Female genital mycotic infection‡‡ 2.7% 13.9% 15.6%
Urinary tract infection 6.8% 10.6% 8.7%
Osmotic diuresis–related AEs§§ 2.1% 5.8% 6.6%
Volume-related AEsll ll 2.3% 1.7% 2.5%
Hypoglycemia 40.9% 6.8% 8.2%
  Glimepiride#
+ metformin (n=482)
INVOKANA® 100 mg + metformin (n=483) INVOKANA® 300 mg + metformin (n=485)
Any AE
78.4% 73.3% 77.9%
AEs leading to discontinuation 7.3% 6.2% 9.5%
AEs related to study drug** 27.8% 28.6% 32.8%
Male genital mycotic infection†† 1.9% 9.5% 9.1%
Female genital mycotic infection‡‡ 2.7% 13.9% 15.6%
Urinary tract infection 6.8% 10.6% 8.7%
Osmotic diuresis–related AEs§§ 2.1% 5.8% 6.6%
Volume-related AEsll ll 2.3% 1.7% 2.5%
Hypoglycemia 40.9% 6.8% 8.2%

All AEs are reported, regardless of rescue drug.
#Mean daily dose=5.6 mg. 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.
††Glimepiride, n=263; INVOKANA® 100 mg, n=252; INVOKANA® 300 mg, n=241; including balanitis, balanitis Candida, balanoposthitis, genital candidiasis, genital infection fungal, and posthitis.
‡‡Glimepiride, n=219; INVOKANA® 100 mg, n=231; INVOKANA® 300 mg, n=244; including genital infection fungal, vaginal infection, vulvitis, vulvovaginal candidiasis, vulvovaginal mycotic infection, and vulvovaginitis.
§§Including dry mouth, micturition urgency, nocturia, pollakiuria, polydipsia, polyuria, thirst, and urine output increased.
|| ||Including BP decreased, dehydration, postural dizziness, hypotension, orthostatic hypotension, presyncope, and syncope.

 

SELECT IMPORTANT SAFETY INFORMATION

  • Hypoglycemia With Concomitant Use With Insulin and Insulin Secretagogues: INVOKANA® can increase the risk of hypoglycemia when combined with insulin or an insulin secretagogue. A lower dose of insulin or insulin secretagogue may be required to minimize the risk of hypoglycemia when used in combination with INVOKANA®.

Study Designs

INVOKANA® vs glimepiride over 52 weeks
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 and the proportion of patients with documented hypoglycemic episodes.1,4

INVOKANA® vs glimepiride over 104 weeks
This randomized, double-blind, active-controlled study consisted of an initial core period, followed by a double-blind extension period of 52 weeks. 1151 patients who completed the 52-week core study entered the second period and continued on the treatments to which they had been randomized. Glimepiride titration was continued throughout the extension period (final mean daily dose=5.6 mg). Secondary endpoints assessed at week 104 included change in A1C, fasting plasma glucose, systolic blood pressure, percent change in body weight, and the proportion of patients who achieved A1C <7.0%. No prespecified hypothesis testing was conducted at week 104; thus, P values were not reported but 95% confidence intervals were reported.3

See results in RENAL IMPAIRMENT

See the results of INVOKANA® AS MONOTHERAPY, VS JANUVIA®, in PATIENTS WITH RENAL IMPAIRMENT, and in OLDER PATIENTS.

References: 1. 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. 2. INVOKANA® [prescribing information]. Titusville, NJ: Janssen Pharmaceuticals, Inc. 3. Data on file. Janssen Pharmaceuticals Inc., Titusville, NJ. 4. Leiter LA, Yoon K-H, Arias P, et al. Canagliflozin provides durable glycemic improvements and body weight reduction over 104 weeks versus glimepiride in patients with type 2 diabetes on metformin: a randomized, double-blind, phase 3 study. Diabetes Care. 2015;38(3):355-364.