Canagliflozin Reduces Cardiovascular Stress in Older Patients With T2D

This article is part of Endocrinology Advisor’s coverage of the American Diabetes Association’s 77th Scientific Sessions (ADA 2017), taking place in San Diego, CA. Our staff will report on medical research and technological advances in diabetes and diabetes education, conducted by experts in the field. Check back regularly for more news from ADA 2017.

The sodium glucose cotransporter-2 (SGLT-2) inhibitor canagliflozin appears to decrease cardiovascular stress in older patients with type 2 diabetes, according to a study presented at the American Diabetes Association (ADA) 77th Scientific Sessions, held June 9-13, 2017 in San Diego, California.¹

SGLT-2 inhibitors are antihyperglycemic agents that decrease glucose reabsorption and thus reduce hyperglycemia without a substantial risk of hypoglycemia. Previous findings suggest that SGLT-2 inhibitors may also reduce other cardiovascular risk factors, such as hypertension, weight, arterial stiffness, and oxidative stress.²

In the present study, researchers conducted an exploratory analysis of a subset of more than 600 patients with type 2 diabetes ranging in age from 55 to 80 years (mean age, 64 years; 56% male; diabetes duration, 12 years). Participants were randomly assigned to receive placebo (n=216), canagliflozin 100 mg/d (n=229), or canagliflozin 300 mg/d (n=221) for a period of 104 weeks.

Serum levels of cardiovascular stress biomarkers N-terminal pro-B type natriuretic peptide (NT-proBNP) and high sensitivity troponin I (hsTnI) were assessed at baseline and at 26, 52, and 104 weeks, and the median change from baseline was examined at each time point.

Similar baseline characteristics were observed in both the placebo and treatment groups. While NT-proBNP increased with placebo from a baseline median of ≈50 pg/mL, minimal change was found with canagliflozin over 104 weeks. The placebo group also demonstrated increases in hsTnl from a baseline median of ≈3.3 pg/mL, while little or no change occurred with canagliflozin.

The median differences between the canagliflozin and placebo groups, based on Hodges-Lehmann estimates (95% CI), were –13.2% (–25.4% to –1.7%) at 26 weeks; –16.3% (–28.9% to –4.0%) at 52 weeks; and –27.6% (–43.2% to –11.5%) at 104 weeks. For hsTnl, the mean differences between groups were –8.3% (–14.0% to –2.5%) at 26 weeks; –11.9% (–18.0% to –5.6%) at 52 weeks; and –10.0% (–17.3% to –2.6%) at 104 weeks (P <.05 for each between-group difference).

“[C]anagliflozin delayed rise in NT-proBNP and hsTnI over 2 years compared with [placebo] in older T2DM patients,” the investigators wrote.

These results are in line with previous findings, suggesting that SGLT-2 inhibitors have a protective effect on cardiovascular risk factors.

Disclosures: The study was supported by Janssen Pharmaceuticals. All authors report financial relationships with various pharmaceutical companies, including Janssen, Novartis, AstraZeneca, Novo Nordisk, and Boehringer Ingelheim, among others. 

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References

1. Januzzi JI, Butler J, Jarolim P, et al. Effects of canagliflozin on biomarkers of cardiovascular stress in older patients with type 2 diabetes mellitus. Presented at: American Diabetes Association (ADA) 77th Scientific Sessions; June 9-13, 2017; San Diego, California. Abstract 150-LB.
2. Inzucchi SE, Zinman B, Wanner C, et al. SGLT-2 inhibitors and cardiovascular risk: Proposed pathways and review of ongoing outcome trials. Diab Vasc Dis Res. 2015;12(2):90-100. doi:10.1177/1479164114559852