The effects of combination canagliflozin and glucagon-like peptide-1 receptor agonist therapy on intermediate markers of cardiovascular risk in the CANVAS program

INTERNATIONAL JOURNAL OF CARDIOLOGY

卷:318

Article

Arnott, Clare^1,2,3,4  Neuen, Brendon L.¹  Heerspink, Hiddo J. L.^2,5  Figtree, Gemma A.^1,4,6,7  Kosiborod, Mikhail⁸  Lam, Carolyn S.^1,5,9,10  Cannon, Christopher P.^11,12  Rosenthal, Norman¹³  Shaw, Wayne¹³  Mahaffey, Kenneth W.¹⁴  Jardine, Meg J.^1,2  Perkovic, Vlado^1,2  Neal, Bruce^1,2 

[1] UNSW Sydney, George Inst Global Hlth, Sydney, NSW, Australia

[2] Univ New South Wales, Sydney, NSW, Australia

[3] Royal Prince Alfred Hosp, Sydney, NSW, Australia

[4] Univ Sydney, Sydney Med Sch, Sydney, NSW, Australia

[5] Univ Groningen, Univ Med Ctr Groningen, Groningen, Netherlands

[6] Royal North Shore Hosp, Kolling Inst, Sydney, NSW, Australia

[7] Univ Sydney, Sydney, NSW, Australia

[8] St Lukes Mid Amer Heart Inst, Kansas City, MO USA

[9] Natl Heart Ctr Singapore, Singapore, Singapore

[10] Duke Natl Univ, Singapore, Singapore

[11] Brigham & Womens Hosp, Cardiovasc Div, Boston, MA 02115 USA

[12] Baim Inst Clin Res, Boston, MA 02115 USA

[13] Janssen Res & Dev LLC, Raritan, NJ 08869 USA

[14] Stanford Univ, Stanford Ctr Clin Res, Dept Med, Sch Med, Stanford, CA 94305 USA

关键词: SGLT2 inhibition;    GLP1 receptor agonist;    Cardiovascular disease, type 2 diabetes;   

DOI  :  10.1016/j.ijcard.2020.06.011

来源: Elsevier

【 摘 要 】

Background: Sodium glucose co-transporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP1-RA) reduce cardiovascular events, and improve intermediate markers of cardiometabolic health, in those with type 2 diabetes. We investigated these effects in the CANVAS Program. Methods and results: The CANVAS Program comprised 2 double-blind, randomized, placebo-controlled trials (CANVAS and CANVAS-R) done in patients with type 2 diabetes and elevated cardiovascular risk. Effects were estimated using mixed-effects models for continuous measures and Cox regression models for other outcomes. Randomized treatment by subgroup interaction terms were used to compare effects of canagliflozin versus placebo across subgroups defined by baseline use of GLP1-RA. There were 10,142 participants, of whom 407 (4%) were using GLP1-RA therapy at baseline. Those using GLP1-RA at baseline were less likely to have a history of cardiovascular disease (60.4% vs 65.8%), had a longer duration of diabetes (152 vs 13.5 years) and a higher body mass index (BMI; 35.6 vs 31.8 kg/m(2)) but were otherwise similar. There were greater reductions with canagliflozin versus placebo for HbA1c (-0.75% versus -0.58%; P = .0091), SBP (-6.26 versus -3.83 mmHg; P = .0018), and body weight (-3.79 versus -2.18 kg; P < .0001) in those on baseline GLP1-RA therapy. Effects across subgroups were similar for UACR (P = .21), eGFR slope (A - .72), major adverse cardiac events (P = .94) and total serious adverse events (P = .74). Conclusions: There may be a synergistic effect of SGLT2 inhibition when used on a background of GLP1-RA for intermediate cardiometabolic markers. (C) 2020 Elsevier B.V. All rights reserved.

【 授权许可】

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