TY - JOUR
AU - Fulcher G.
AU - de Zeeuw D.
AU - Desai M.
AU - Shaw W.
AU - Vercruysse F.
AU - Meininger G.
AU - Mahaffey K.
AU - Capuano G.
AU - Rosenstock J.
AU - Matthews D.
AU - Weiss R.
AU - Perkovic Vlado
AU - Neal Bruce
AB - <p>
INTRODUCTION: The efficacy and safety of canagliflozin, a sodium glucose co-transporter 2 (SGLT2) inhibitor, was evaluated in patients with type 2 diabetes mellitus (T2DM) inadequately controlled on sulfonylurea monotherapy. METHODS: The CANagliflozin cardioVascular Assessment Study (CANVAS) is a double-blind, placebo-controlled cardiovascular outcomes study that randomized participants to placebo or canagliflozin 100 or 300 mg once daily in addition to routine therapy. Participants in the CANVAS trial are men and women aged &gt;/=30 years with T2DM and a history or high risk of cardiovascular disease, and inadequate glycemic control (glycated hemoglobin [HbA1c] &gt;/=7.0% and <!--=10.5%) on current antihyperglycemic therapies. The primary objective of this prespecified substudy was to assess change from baseline to 18 weeks in HbA1c among patients on sulfonylurea monotherapy. RESULTS: Of the 4330 patients enrolled in CANVAS, 127 met the entry criteria for the sulfonylurea monotherapy substudy (placebo, n = 45; canagliflozin 100 mg, n = 42; canagliflozin 300 mg, n = 40). At 18 weeks, placebo-subtracted changes (95% confidence interval) in HbA1c were -0.74% (-1.15, -0.33; P < 0.001) and -0.83% (-1.24, -0.42; P < 0.001) with canagliflozin 100 and 300 mg, respectively. Relative to placebo, canagliflozin 100 and 300 mg also decreased fasting plasma glucose (FPG; -2.1 mmol/L [-3.0, -1.2] and -2.7 mmol/L [-3.6, -1.7], respectively). Body weight was lower with canagliflozin 300 mg (-1.8% [-3.2, -0.4]; P = 0.014) but unchanged with canagliflozin 100 mg (-0.4% [-1.8, 1.0]; P = 0.557). Canagliflozin 300 mg increased hypoglycemia episodes compared to canagliflozin 100 mg and placebo (15%, 0%, and 4.4%, respectively). Adverse events (AEs) of male and female genital mycotic infections, pollakiuria, and thirst were more common with canagliflozin. CONCLUSIONS: Canagliflozin added to ongoing sulfonylurea monotherapy produced improvements in HbA1c, FPG, and body weight, with an increased incidence of AEs consistent with the mechanism of action of SGLT2 inhibition. FUNDING: Janssen Research & Development, LLC. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT01032629.-->
</p>

AD - The Royal North Shore Hospital and University of Sydney, Sydney, Australia, greg.fulcher@sydney.edu.au.
AN - 26081793
BT - Diabetes Ther
DP - NLM
ET - 2015/06/18
LA - Eng
LB - R&M<br/>FP<br/>AUS
M1 - 3
N1 - Fulcher, Greg<br/>Matthews, David R<br/>Perkovic, Vlado<br/>de Zeeuw, Dick<br/>Mahaffey, Kenneth W<br/>Weiss, Robert<br/>Rosenstock, Julio<br/>Capuano, George<br/>Desai, Mehul<br/>Shaw, Wayne<br/>Vercruysse, Frank<br/>Meininger, Gary<br/>Neal, Bruce<br/>Diabetes Ther. 2015 Jun 17.
N2 - <p>
INTRODUCTION: The efficacy and safety of canagliflozin, a sodium glucose co-transporter 2 (SGLT2) inhibitor, was evaluated in patients with type 2 diabetes mellitus (T2DM) inadequately controlled on sulfonylurea monotherapy. METHODS: The CANagliflozin cardioVascular Assessment Study (CANVAS) is a double-blind, placebo-controlled cardiovascular outcomes study that randomized participants to placebo or canagliflozin 100 or 300 mg once daily in addition to routine therapy. Participants in the CANVAS trial are men and women aged &gt;/=30 years with T2DM and a history or high risk of cardiovascular disease, and inadequate glycemic control (glycated hemoglobin [HbA1c] &gt;/=7.0% and <!--=10.5%) on current antihyperglycemic therapies. The primary objective of this prespecified substudy was to assess change from baseline to 18 weeks in HbA1c among patients on sulfonylurea monotherapy. RESULTS: Of the 4330 patients enrolled in CANVAS, 127 met the entry criteria for the sulfonylurea monotherapy substudy (placebo, n = 45; canagliflozin 100 mg, n = 42; canagliflozin 300 mg, n = 40). At 18 weeks, placebo-subtracted changes (95% confidence interval) in HbA1c were -0.74% (-1.15, -0.33; P < 0.001) and -0.83% (-1.24, -0.42; P < 0.001) with canagliflozin 100 and 300 mg, respectively. Relative to placebo, canagliflozin 100 and 300 mg also decreased fasting plasma glucose (FPG; -2.1 mmol/L [-3.0, -1.2] and -2.7 mmol/L [-3.6, -1.7], respectively). Body weight was lower with canagliflozin 300 mg (-1.8% [-3.2, -0.4]; P = 0.014) but unchanged with canagliflozin 100 mg (-0.4% [-1.8, 1.0]; P = 0.557). Canagliflozin 300 mg increased hypoglycemia episodes compared to canagliflozin 100 mg and placebo (15%, 0%, and 4.4%, respectively). Adverse events (AEs) of male and female genital mycotic infections, pollakiuria, and thirst were more common with canagliflozin. CONCLUSIONS: Canagliflozin added to ongoing sulfonylurea monotherapy produced improvements in HbA1c, FPG, and body weight, with an increased incidence of AEs consistent with the mechanism of action of SGLT2 inhibition. FUNDING: Janssen Research & Development, LLC. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT01032629.-->
</p>

PY - 2015
SN - 1869-6953 (Print)
SP - 289
EP - 302
T2 - Diabetes Ther
TI - Efficacy and Safety of Canagliflozin Used in Conjunction with Sulfonylurea in Patients with Type 2 Diabetes Mellitus: A Randomized, Controlled Trial
VL - 6
Y2 - FY16
ER -