• Lawrence A Leiter, Kun-Ho Yoon, Pablo Arias, Gisle Langslet, John Xie, Dainius A Balis, Dawn Millington, Frank Vercruysse, William Canovatchel, and Gary Meininger.
• Keenan Research Centre, The Li Ka Shing Knowledge Institute, St. Michael's Hospital; Division of Endocrinology and Metabolism, University of Toronto, Toronto, Ontario, Canada leiterl@smh.ca.
• Diabetes Care. 2015 Mar 1;38(3):355-64.

ObjectiveTo assess the efficacy/safety of canagliflozin, a sodium-glucose cotransporter 2 inhibitor, compared with glimepiride over 104 weeks in patients with type 2 diabetes inadequately controlled with metformin.Research Design And MethodsIn this randomized, double-blind study, patients (N = 1,450) received canagliflozin 100 or 300 mg or glimepiride (titrated up to 6 or 8 mg/day) during a 52-week core period followed by a 52-week extension.ResultsAt week 104, reductions from baseline in A1C were -0.65%, -0.74%, and -0.55% (-7.1, -8.1, and -6.0 mmol/mol) with canagliflozin 100 and 300 mg and glimepiride, respectively. Durability analyses showed sustained A1C lowering with both canagliflozin doses versus glimepiride. Reductions in body weight (-4.1%, -4.2%, and 0.9%, respectively) and systolic blood pressure (-2.0, -3.1, and 1.7 mmHg, respectively) were seen with canagliflozin 100 and 300 mg compared with glimepiride at week 104. The overall adverse event (AE) incidence was 73.3%, 77.9%, and 78.4% with canagliflozin 100 and 300 mg and glimepiride; the incidence of AE-related discontinuations was low across groups (6.2%, 9.5%, and 7.3%, respectively). Incidences of genital mycotic infections, urinary tract infections, and osmotic diuresis-related AEs were higher with canagliflozin than glimepiride; these were generally mild to moderate in intensity and led to few discontinuations. Fewer patients had hypoglycemia episodes with canagliflozin 100 and 300 mg than glimepiride (6.8%, 8.2%, and 40.9%). Mild decreases in estimated glomerular filtration rate occurred initially with canagliflozin; these attenuated over 104 weeks.ConclusionsCanagliflozin provided durable glycemic improvements compared with glimepiride and was generally well tolerated in patients with type 2 diabetes receiving background treatment with metformin over 104 weeks.© 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

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