Efficacy and safety of canagliflozin when used in conjunction with incretin-mimetic therapy in patients with type 2 diabetes

CANVAS trial collaborative group; L. Gnudi

doi:10.1111/dom.12589

Efficacy and safety of canagliflozin when used in conjunction with incretin-mimetic therapy in patients with type 2 diabetes

CANVAS trial collaborative group, L. Gnudi

Research output: Contribution to journal › Article › peer-review

78 Citations (Scopus)

Abstract

Aims To assess the efficacy and safety of canagliflozin, a sodium glucose co-transporter 2 (SGLT2) inhibitor, in patients with type 2 diabetes enrolled in the CANagliflozin cardioVascular Assessment Study (CANVAS) who were on an incretin mimetic [dipeptidyl peptidase-4 (DPP-4) inhibitor or glucagon-like peptide-1 (GLP-1) receptor agonist]. Methods CANVAS is a double-blind, placebo-controlled study that randomized participants to canagliflozin 100 or 300 mg or placebo added to routine therapy. The present post hoc analysis assessed the efficacy and safety of canagliflozin 100 and 300 mg compared with placebo in subsets of patients from CANVAS who were taking background DPP-4 inhibitors or GLP-1 receptor agonists with or without other antihyperglycaemic agents at week 18. Results Of the 4330 patients in CANVAS, 316 were taking DPP-4 inhibitors and 95 were taking GLP-1 receptor agonists. At 18 weeks, canagliflozin 100 and 300 mg provided larger placebo-subtracted reductions in glycated haemoglobin (HbA1c) in patients taking DPP-4 inhibitors [−0.56% (95% confidence interval [CI]: −0.77, −0.35), and −0.75% (95% CI: −0.95, −0.54), respectively] and GLP-1 receptor agonists [−1.00% (95% CI: −1.35, −0.65), and −1.06% (95% CI: −1.43, −0.69), respectively]. Body weight and blood pressure (BP) reductions were seen with canagliflozin versus placebo in both subsets. Higher incidences of genital mycotic infections and osmotic diuresis–related adverse events (AEs) were seen with canagliflozin compared with placebo. The incidence of hypoglycaemia was numerically higher with canagliflozin versus placebo; nearly all events occurred in patients on background insulin or insulin secretagogues. Conclusions In patients on background incretin mimetics, canagliflozin improved HbA1c, body weight and BP, with an increased incidence of AEs related to SGLT2 inhibition.

Original language	Undefined/Unknown
Pages (from-to)	82-91
Number of pages	10
Journal	Diabetes, obesity & metabolism
Volume	18
Issue number	1
Early online date	9 Oct 2015
DOIs	https://doi.org/10.1111/dom.12589
Publication status	Published - Jan 2016

Keywords

canagliflozin, type 2 diabetes

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1111/dom.12589

http://dx.doi.org/10.1111/dom.12589

Cite this

@article{306f0431e7e74bc7abd4bae423c071ea,

title = "Efficacy and safety of canagliflozin when used in conjunction with incretin-mimetic therapy in patients with type 2 diabetes",

abstract = "Aims To assess the efficacy and safety of canagliflozin, a sodium glucose co-transporter 2 (SGLT2) inhibitor, in patients with type 2 diabetes enrolled in the CANagliflozin cardioVascular Assessment Study (CANVAS) who were on an incretin mimetic [dipeptidyl peptidase-4 (DPP-4) inhibitor or glucagon-like peptide-1 (GLP-1) receptor agonist]. Methods CANVAS is a double-blind, placebo-controlled study that randomized participants to canagliflozin 100 or 300 mg or placebo added to routine therapy. The present post hoc analysis assessed the efficacy and safety of canagliflozin 100 and 300 mg compared with placebo in subsets of patients from CANVAS who were taking background DPP-4 inhibitors or GLP-1 receptor agonists with or without other antihyperglycaemic agents at week 18. Results Of the 4330 patients in CANVAS, 316 were taking DPP-4 inhibitors and 95 were taking GLP-1 receptor agonists. At 18 weeks, canagliflozin 100 and 300 mg provided larger placebo-subtracted reductions in glycated haemoglobin (HbA1c) in patients taking DPP-4 inhibitors [−0.56% (95% confidence interval [CI]: −0.77, −0.35), and −0.75% (95% CI: −0.95, −0.54), respectively] and GLP-1 receptor agonists [−1.00% (95% CI: −1.35, −0.65), and −1.06% (95% CI: −1.43, −0.69), respectively]. Body weight and blood pressure (BP) reductions were seen with canagliflozin versus placebo in both subsets. Higher incidences of genital mycotic infections and osmotic diuresis–related adverse events (AEs) were seen with canagliflozin compared with placebo. The incidence of hypoglycaemia was numerically higher with canagliflozin versus placebo; nearly all events occurred in patients on background insulin or insulin secretagogues. Conclusions In patients on background incretin mimetics, canagliflozin improved HbA1c, body weight and BP, with an increased incidence of AEs related to SGLT2 inhibition.",

keywords = "canagliflozin, type 2 diabetes",

author = "G. Fulcher and Matthews, {D. R.} and V. Perkovic and {de Zeeuw}, D. and Mahaffey, {K. W.} and C. Mathieu and V. Woo and C. Wysham and G. Capuano and M. Desai and W. Shaw and F. Vercruysse and G. Meininger and B. Neal and {CANVAS trial collaborative group} and L. Gnudi",

note = "DOM-15-0529-OP.R1",

year = "2016",

month = jan,

doi = "10.1111/dom.12589",

language = "Undefined/Unknown",

volume = "18",

pages = "82--91",

journal = "Diabetes, obesity & metabolism",

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TY - JOUR

T1 - Efficacy and safety of canagliflozin when used in conjunction with incretin-mimetic therapy in patients with type 2 diabetes

AU - Fulcher, G.

AU - Matthews, D. R.

AU - Perkovic, V.

AU - de Zeeuw, D.

AU - Mahaffey, K. W.

AU - Mathieu, C.

AU - Woo, V.

AU - Wysham, C.

AU - Capuano, G.

AU - Desai, M.

AU - Shaw, W.

AU - Vercruysse, F.

AU - Meininger, G.

AU - Neal, B.

AU - CANVAS trial collaborative group

AU - Gnudi, L.

N1 - DOM-15-0529-OP.R1

PY - 2016/1

Y1 - 2016/1

N2 - Aims To assess the efficacy and safety of canagliflozin, a sodium glucose co-transporter 2 (SGLT2) inhibitor, in patients with type 2 diabetes enrolled in the CANagliflozin cardioVascular Assessment Study (CANVAS) who were on an incretin mimetic [dipeptidyl peptidase-4 (DPP-4) inhibitor or glucagon-like peptide-1 (GLP-1) receptor agonist]. Methods CANVAS is a double-blind, placebo-controlled study that randomized participants to canagliflozin 100 or 300 mg or placebo added to routine therapy. The present post hoc analysis assessed the efficacy and safety of canagliflozin 100 and 300 mg compared with placebo in subsets of patients from CANVAS who were taking background DPP-4 inhibitors or GLP-1 receptor agonists with or without other antihyperglycaemic agents at week 18. Results Of the 4330 patients in CANVAS, 316 were taking DPP-4 inhibitors and 95 were taking GLP-1 receptor agonists. At 18 weeks, canagliflozin 100 and 300 mg provided larger placebo-subtracted reductions in glycated haemoglobin (HbA1c) in patients taking DPP-4 inhibitors [−0.56% (95% confidence interval [CI]: −0.77, −0.35), and −0.75% (95% CI: −0.95, −0.54), respectively] and GLP-1 receptor agonists [−1.00% (95% CI: −1.35, −0.65), and −1.06% (95% CI: −1.43, −0.69), respectively]. Body weight and blood pressure (BP) reductions were seen with canagliflozin versus placebo in both subsets. Higher incidences of genital mycotic infections and osmotic diuresis–related adverse events (AEs) were seen with canagliflozin compared with placebo. The incidence of hypoglycaemia was numerically higher with canagliflozin versus placebo; nearly all events occurred in patients on background insulin or insulin secretagogues. Conclusions In patients on background incretin mimetics, canagliflozin improved HbA1c, body weight and BP, with an increased incidence of AEs related to SGLT2 inhibition.

AB - Aims To assess the efficacy and safety of canagliflozin, a sodium glucose co-transporter 2 (SGLT2) inhibitor, in patients with type 2 diabetes enrolled in the CANagliflozin cardioVascular Assessment Study (CANVAS) who were on an incretin mimetic [dipeptidyl peptidase-4 (DPP-4) inhibitor or glucagon-like peptide-1 (GLP-1) receptor agonist]. Methods CANVAS is a double-blind, placebo-controlled study that randomized participants to canagliflozin 100 or 300 mg or placebo added to routine therapy. The present post hoc analysis assessed the efficacy and safety of canagliflozin 100 and 300 mg compared with placebo in subsets of patients from CANVAS who were taking background DPP-4 inhibitors or GLP-1 receptor agonists with or without other antihyperglycaemic agents at week 18. Results Of the 4330 patients in CANVAS, 316 were taking DPP-4 inhibitors and 95 were taking GLP-1 receptor agonists. At 18 weeks, canagliflozin 100 and 300 mg provided larger placebo-subtracted reductions in glycated haemoglobin (HbA1c) in patients taking DPP-4 inhibitors [−0.56% (95% confidence interval [CI]: −0.77, −0.35), and −0.75% (95% CI: −0.95, −0.54), respectively] and GLP-1 receptor agonists [−1.00% (95% CI: −1.35, −0.65), and −1.06% (95% CI: −1.43, −0.69), respectively]. Body weight and blood pressure (BP) reductions were seen with canagliflozin versus placebo in both subsets. Higher incidences of genital mycotic infections and osmotic diuresis–related adverse events (AEs) were seen with canagliflozin compared with placebo. The incidence of hypoglycaemia was numerically higher with canagliflozin versus placebo; nearly all events occurred in patients on background insulin or insulin secretagogues. Conclusions In patients on background incretin mimetics, canagliflozin improved HbA1c, body weight and BP, with an increased incidence of AEs related to SGLT2 inhibition.

KW - canagliflozin, type 2 diabetes

U2 - 10.1111/dom.12589

DO - 10.1111/dom.12589

M3 - Article

SN - 1463-1326

VL - 18

SP - 82

EP - 91

JO - Diabetes, obesity & metabolism

JF - Diabetes, obesity & metabolism

IS - 1

ER -