SGLT2 Inhibitor Offers CV, Renal Protection in High-risk Patients

November 3, 2017

Significant reductions were seen in MACE, renal disease progression in patients with high CV risk taking canagliflozin.

References:

1. Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015; 373: 2117-28.2. Wanner C, Inzucchi SE, Lachin JM, et al. Empagliflozin and progression of kidney disease in type 2 diabetes. N Engl J Med. 2016; 375: 323-34.3. Wu JH, Foote C, Blomster J, et al. Effects of sodium-glucose cotransporter-2 inhibitors on cardiovascular events, death, and major safety outcomes in adults with type 2 diabetes: a systematic review and meta-analysis. Lancet Diabetes Endocrinol. 2016; 4:411-9.4. Neal B, Perkovic V, Mahaffey KW, de Zeeuw D, et al. for the CANVAS Program Collaborative Group. Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes. N Engl J Med. 2017;377:644-657. doi: 10.1056/NEJMoa1611925.

CANVAS: Canagliflozin Cardiovascular Assessment Study, including Renal Outcomes

SGLT2 inhibitors linked to:Improved blood pressure, body weight, albuminuria, intraglomerular pressure, volume overload; also decreased risk of renal disease progression, CV death and all-cause death^.

CANVAS: Canagliflozin Cardiovascular Assessment Study:Pooled data from two trials conducted at 667 centers in 30 countries; 10,142 participants with T2D at high CV risk; 65.6% with CVD.

Improved CV outcomes, suggested renal protection: 3-point MACE: 14% lower with CANA vs placebo; renal: outcomes not statistically significant, but suggest possible benefit of CANA.

Adverse reactions consistent with previously reported SGLT2i risk: Genitourinary infections, volume depletion, diuresis, fractures; however, also found increased risk of amputations

Study limitations include that 29.9% of the placebo group discontinued randomized therapy and used other glucose-lowering agents; could underestimate risks/benefits of CANA

CANVAS suggests significantly lower risk of MACE in patients with T2D at high CV risk; renal outcomes support possible renal protection as class effect; CREDENCE trial ongoing.

CANVAS take-home points: Results suggest significantly lower risk of CV death, nonfatal MI, or nonfatal stroke in patients with T2D at high CV risk, vs placebo. Improved renal outcomes suggest protective role for SGLT2 inhibitors; more evidence will be provided from the ongoing CREDENCE trial. Safety signal for increased risk for amputations with CANA vs placebo.