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.
Author(s): Cefalu WT(1), Leiter LA, Yoon KH, Arias P, Niskanen L, Xie J, Balis DA,
Canovatchel W, Meininger G.
Affiliation(s): Author information:
(1)Pennington Biomedical Research Center, Baton Rouge, LA 70808, USA.
william.cefalu@pbrc.edu
Publication date & source: 2013, Lancet. , 382(9896):941-50
BACKGROUND: Sodium-glucose cotransporter 2 (SGLT2) inhibitors improve glycaemia
in patients with type 2 diabetes by enhancing urinary glucose excretion. We
compared the efficacy and safety of canagliflozin, an SGLT2 inhibitor, with
glimepiride in patients with type 2 diabetes inadequately controlled with
metformin.
METHODS: We undertook this 52 week, randomised, double-blind, active-controlled,
phase 3 non-inferiority trial at 157 centres in 19 countries between Aug 28,
2009, and Dec 21, 2011. Patients aged 18-80 years with type 2 diabetes and
glycated haemoglobin A1c (HbA1c) of 7·0-9·5% on stable metformin were randomly
assigned (1:1:1) by computer-generated random sequence via an interactive voice
or web response system to receive canagliflozin 100 mg or 300 mg, or glimepiride
(up-titrated to 6 mg or 8 mg per day) orally once daily. Patients, study
investigators, and local sponsor personnel were masked to treatment. The primary
endpoint was change in HbA1c from baseline to week 52, with a non-inferiority
margin of 0·3% for the comparison of each canagliflozin dose with glimepiride. If
non-inferiority was shown, we assessed superiority on the basis of an upper bound
of the 95% CI for the difference of each canagliflozin dose versus glimepiride of
less than 0·0%. Analysis was done in a modified intention-to-treat population,
including all randomised patients who received at least one dose of study drug.
This study is registered with ClinicalTrials.gov, number NCT00968812.
FINDINGS: 1450 of 1452 randomised patients received at least one dose of
glimepiride (n=482), canagliflozin 100 mg (n=483), or canagliflozin 300 mg
(n=485). For lowering of HbA1c at 52 weeks, canagliflozin 100 mg was non-inferior
to glimepiride (least-squares mean difference -0·01% [95% CI -0·11 to 0·09]), and
canagliflozin 300 mg was superior to glimepiride (-0·12% [-0·22 to -0·02]). 39
(8%) patients had serious adverse events in the glimepiride group versus 24 (5%)
in the canagliflozin 100 mg group and 26 (5%) in the 300 mg group. In the
canagliflozin 100 mg and 300 mg groups versus the glimepiride group, we recorded
a greater number of genital mycotic infections (women: 26 [11%] and 34 [14%] vs
five [2%]; men: 17 [7%] and 20 [8%] vs three [1%]), urinary tract infections (31
[6%] for both canagliflozin doses vs 22 [5%]), and osmotic diuresis-related
events (pollakiuria: 12 [3%] for both doses vs one [<1%]; polyuria: four [<1%]
for both doses vs two [<1%]).
INTERPRETATION: Canagliflozin provides greater HbA1c reduction than does
glimepiride, and is well tolerated in patients with type 2 diabetes receiving
metformin. These findings support the use of canagliflozin as a viable treatment
option for patients who do not achieve sufficient glycaemic control with
metformin therapy.
FUNDING: Janssen Research & Development, LLC.
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