Canagliflozin attenuates biomarkers tied to adverse CV outcomes in T2DM patients
Treatment with canagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor, impedes the rise in serum N-terminal pro‒B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin I (hsTnI) in older patients with type 2 diabetes mellitus (T2DM) for over 2 years, according to a recent study.
“Our findings suggest that canagliflozin treatment was associated with attenuation of biomarkers associated with adverse cardiovascular (CV) outcomes in this study population of older patients with T2DM,” researchers said.
“These cardiac biomarker data provide support for the beneficial cardiovascular effect of sodium glucose cotransporter 2 inhibitors in T2DM,” they added.
To examine the effects of canagliflozin on CV biomarkers in older patients with T2DM, 666 participants were randomly assigned to receive canagliflozin 100 or 300 mg or placebo. Researchers evaluated the median percent change in NT-proBNP, hsTnI, soluble (s)ST2 and galectin-3 from baseline to 26, 52 and 104 weeks.
Placebo recipients had increased levels of both serum NT-proBNP and serum hsTnI, but those receiving canagliflozin had largely unchanged levels of such biomarkers. [J Am Coll Cardiol 2017;doi:10.1016/j.jacc.2017.06.016]
At weeks 26, 52 and 104, Hodges-Lehmann estimates of the difference in median percent change between pooled canagliflozin and placebo were ‒15.0, ‒16.1 and ‒26.8 percent for NT-proBNP and ‒8.3, ‒11.9 and ‒10.0 percent for hsTnI, respectively (p<0.05 for all).
Serum sST2 level did not change with canagliflozin and placebo over 104 weeks. On the other hand, there was a modest increase in serum galentic-3 from baseline with canagliflozin vs placebo, with significant differences seen at 26 and 52 weeks but not at 104 weeks.
When assessing only those with complete samples, these results remained unchanged.
“[W]e found that serum concentrations of NT-proBNP and hsTnI, biomarkers with proven prognostic value for cardiovascular risk in T2DM, rose over a 2-year period in patients allocated to placebo, whereas canagliflozin treatment attenuated their rise,” researchers said.
“In contrast, we found no obvious effect of treatment with canagliflozin on concentrations of sST2, with a modest, nonpersistent rise in galectin-3,” they added.
The effects of canagliflozin vs placebo on serum concentrations of NT-proBNP and hsTnI are similar with the attenuation of CV risk in patients treated with SGLT2 inhibitors, which have been recently studied in large CV outcomes trials for assessing the CV effects of newer T2DM agents. [https://www.fda.gov/downloads/Drugs/.../Guidances/ucm071627.pdf]
In the EMPA-REG OUTCOME (Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients) study, empagliflozin treatment reduced the risk of major adverse cardiovascular events (CV death, nonfatal stroke and nonfatal myocardial infarction) vs placebo, driven by a 38-percent reduction in CV death and 35-percent decrease in the risk of hospitalization for heart failure. [N Engl J Med 373:2117–2128]
“To the extent that it is unclear whether benefits seen in the EMPA-REG OUTCOME study could be expected from treatment with all SGLT2 inhibitors, our results provide novel data regarding possible cardiovascular benefits from canagliflozin treatment,” researchers noted.
“Further studies are needed to understand the mechanisms by which SGLT2 inhibitors ameliorate myocardial stress and prevent necrosis in patients with T2DM and to clarify how biomarkers can be optimally utilized to guide therapy,” they added.