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

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• 作者：William T Cefalu ; Lawrence A Leiter ; Kun-Ho Yoon ; Pablo Arias ; Leo Niskanen ; John Xie ; Dainius A Balis ; William Canovatchel ; Gary Meininger
• 刊名：The Lancet
• 出版年：2013
• 出版时间：14-20 September, 2013
• 年：2013
• 卷：382
• 期：9896
• 页码：941-950
• 全文大小：491 K

文摘

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Summary

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 A_1c (HbA_1c) 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 HbA_1c 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 , number .

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 HbA_1c 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 HbA_1c 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.