You are here

INVOKAMET® XR demonstrated a similar overall tolerability profile and incidence of hypoglycemia to metformin XR alone1,2

Overall Safety and Select Adverse Events With INVOKAMET® XR and INVOKANA® vs Metformin XR Over 26 Weeks1,2

  Metformin XR*
(n=237)
INVOKANA® 100 mg/
metformin XR*
(n=237)
INVOKANA® 300 mg/metformin XR*
(n=237)
INVOKANA® 100 mg (n=237) INVOKANA® 300 mg (n=238)
Any AE 37.6% 41.8% 44.3% 37.1% 39.9%
AEs leading to discontinuation 1.7% 1.7% 3.0% 1.3% 2.9%
AEs related to study drug 7.2% 6.3% 14.8% 10.1% 9.2%
Serious AEs related to study drug 0% 0% 0% 0% 0.8%
Urinary tract infection 1.3% 1.3% 3.0% 1.3% 2.1%
Incidence of hypoglycemia 4.6% 4.2% 5.5% 3.0% 3.8%
Male genital mycotic infection 0% 0.9% 1.7% 1.9% 4.0%
Female genital mycotic infection§ 0% 2.3% 3.3% 2.3% 4.4%
Osmotic diuresis–related AEs|| 0.8% 0.8% 2.5% 2.1% 1.7%
Volume depletion–related AEs 0.4% 1.7% 0.8% 0.4% 1.3%
Renal-related AEs# 0% 0.4% 1.3% 3.0% 1.3%
Diarrhea 1.3% 4.2% 4.2% 1.3% 1.7%
  Metformin XR*
(n=237)
INVOKANA® 100 mg/
metformin XR*
(n=237)
INVOKANA® 300 mg/metformin XR*
(n=237)
Any AE 37.6% 41.8% 44.3%
AEs leading to discontinuation 1.7% 1.7% 3.0%
AEs related to study drug 7.2% 6.3% 14.8%
Serious AEs related to study drug 0% 0% 0%
Urinary tract infection 1.3% 1.3% 3.0%
Incidence of hypoglycemia 4.6% 4.2% 5.5%
Male genital mycotic infection 0% 0.9% 1.7%
Female genital mycotic infection§ 0% 2.3% 3.3%
Osmotic diuresis–related AEs|| 0.8% 0.8% 2.5%
Volume depletion–related AEs 0.4% 1.7% 0.8%
Renal-related AEs# 0% 0.4% 1.3%
Diarrhea 1.3% 4.2% 4.2%
  Metformin XR*
(n=237)
INVOKANA® 100 mg (n=237) INVOKANA® 300 mg (n=238)
Any AE 37.6% 37.1% 39.9%
AEs leading to discontinuation 1.7% 1.3% 2.9%
AEs related to study drug 7.2% 10.1% 9.2%
Serious AEs related to study drug 0% 0% 0.8%
Urinary tract infection 1.3% 1.3% 2.1%
Incidence of hypoglycemia 4.6% 3.0% 3.8%
Male genital mycotic infection 0% 1.9% 4.0%
Female genital mycotic infection§ 0% 2.3% 4.4%
Osmotic diuresis–related AEs|| 0.8% 2.1% 1.7%
Volume depletion–related AEs 0.4% 0.4% 1.3%
Renal-related AEs# 0% 3.0% 1.3%
Diarrhea 1.3% 1.3% 1.7%

*Metformin XR titration up to 2000 mg/day was allowed through week 9 of the study. At week 26, the mean dose of metformin XR was 1924, 1909, and 1930 mg/day in the INVOKANA® 100 mg/metformin XR, INVOKANA® 300 mg/metformin XR, and metformin XR groups, respectively. The doses of INVOKANA® were not titrated.1
Possibly, probably, or very likely related to study drug, as assessed by investigators.
Metformin XR, n=116; INVOKANA® 100 mg + metformin XR, n=108; INVOKANA® 300 mg + metformin XR, n=115; INVOKANA® 100 mg, n=105; INVOKANA® 300 mg, n=125; includes balanoposthitis, genital candidiasis, and genital fungal infection.
§Metformin XR, n=121; INVOKANA® 100 mg + metformin XR, n=129; INVOKANA® 300 mg + metformin XR, n=122; INVOKANA® 100 mg, n=132; INVOKANA® 300 mg, n=113; includes genital infection female, vaginal infection, vulvitis, vulvovaginal candidiasis, vulvovaginal mycotic infection, and vulvovaginitis.
||Includes dry mouth, pollakiuria, polyuria, and thirst.
Includes dehydration, dizziness postural, hypotension, orthostatic hypotension, and syncope.
#Includes blood creatinine increased, glomerular filtration rate decreased, and renal impairment.

Percent of Patients With Documented Hypoglycemia Over 26 Weeks1


Percent of patients with documented hypoglycemia

*Metformin XR titration up to 2000 mg/day was allowed through week 9 of the study. At week 26, the mean dose of metformin XR was 1924, 1909, and 1930 mg/day in the INVOKANA® 100 mg/metformin XR, INVOKANA® 300 mg/metformin XR, and metformin XR groups, respectively. The doses of INVOKANA® were not titrated.1

Study Design

A randomized, double-blind, 26-week phase 3 study of 1186 patients with type 2 diabetes not on antihyperglycemic agent (AHA) therapy or off AHA therapy for ≥12 weeks before screening. The patients’ diabetes was inadequately controlled with diet and exercise. Patients were randomized and received ≥1 dose of canagliflozin 100 mg plus metformin XR (n=237), canagliflozin 300 mg plus metformin XR (n=237), canagliflozin 100 mg alone (n=237), canagliflozin 300 mg alone (n=238), or metformin XR alone (n=237). During the double-blind treatment period, patients in all treatment groups were instructed to take 2 capsules of canagliflozin or matching placebo each day, 1 capsule taken before a morning meal and 1 capsule taken with the evening meal. Those receiving metformin XR alone or with canagliflozin were titrated up to 2000 mg/day over the first 9 weeks; the doses of canagliflozin were not titrated. The prespecified primary endpoint was the change in A1C at 26 weeks.1

See POOLED SAFETY 

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

References: 1. Rosenstock J, Chuck L, González-Ortiz M, et al. Initial combination therapy with canagliflozin plus metformin versus each component as monotherapy for drug-naïve type 2 diabetes. Diabetes Care. 2016;39(3):353-362. 2. Data on file. Janssen Pharmaceuticals, Inc., Titusville, NJ.