Monday , December 18 2017
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New Information on SGLT-2 Inhibitors

Research presented at the American Heart Association provided new insight into  two large diabetes drug trials, CANVAS and EMPA-REG OUTCOME.

It’s been established that SGLT-2 therapies for type 2 diabetes  appear to have a class effect that reduces cardiovascular risk. Though the mechanism of action is not yet known, research has shown canagliflozin to reduce the combined risk of CV death, nonfatal MI and nonfatal stroke by 14 percent, with empagliflozin showing a 38% reduction.

More information about the effectiveness of this drug class was yielded through two large trials: the EMPA-REG OUTCOME, the 2015 cardiovascular outcomes trial for empagliflozin, and CANVAS, the June 2017 counterpart for canagliflozin. Researchers presented the results and the implications for high-risk patients at the 2017 American Heart Association Scientific Sessions in Anaheim, California.

The two trials have one important difference in their populations: while one third of the 10,142 patients in CANVAS did not have a history of CV disease, all of the 7,020 patients in the EMPA-REG OUTCOME trial did. When results for CANVAS were reported in June, the study’s lead author said that there was no indication the drug was behaving differently in the two populations. Kenneth W. Mahaffey, MD, of Stanford University, presented new findings for canagliflozin which support this premise.  The results showed that the SGLT-2 inhibitor was effective in reducing the risk of CV outcomes in patients with and without a prior history of cardiovascular disease. Patients in the primary prevention group—those with CV risk factors, but not disease—had a hazard ratio (HR) of 0.98 (95% confidence interval [CI]: 0.74 to 1.30), while those in the secondary prevention group—those with a history of CV disease—had a HR of 0.82 (95% CI: 0.72 to 0.95).

James F. List, MD, PhD, Janssen global therapeutic area of Cardiovascular and Metabolism, noted in a statement “All people with type 2 diabetes have an increased risk of developing cardiovascular and renal diseases. This new CANVAS analysis is clinically important, because it shows that canagliflozin may offer a broad range of patients an effective treatment option to reduce their risk of cardiovascular and renal disease.”

Further, in the journal Circulation, the study’s authors concluded, “Canagliflozin reduced cardiovascular and renal outcomes with no statistical evidence of heterogeneity of the treatment effect across the primary and secondary prevention groups.”

At the AHA session, new results for empagliflozin were presented, indicating substantial benefits for patients with peripheral artery disease (PAD), a serious complication of T2D that can lead to amputations. Patients with PAD accounted for 21% of the study population in EMPA-REG, and these patients experienced even greater reductions in CV events, including CV death, than the overall study group. Patients with PAD in the trial experienced:

  • A 43% reduction in CV death
  • A 44% reduction in hospitalization for heart failure
  • A 38% reduction in death for any cause
  • A 16% reduction in 3-point MACE (major adverse cardiovascular event, which includes CV death, non-fatal heart attack, or non-fatal stroke)
  • A 46% reduction in new or worsening kidney disease.

Researchers are also looking at canagliflozin’s benefits for renal outcomes. A separate trial, called CREDENCE, is fully enrolled, and will look specifically at canagliflozin in patients with diabetic nephropathy. 

Practice Pearls:

  • Empaglifozin showed substantial benefits for patients with peripheral artery disease (PAD), a serious complication of T2D that can lead to amputations.
  • A third of the 10,142 patients in CANVAS did not have a history of CV disease, while all of the 7,020 patients in the EMPA-REG OUTCOME trial did.
  • This CANVAS analysis showed that canaglifozin may offer a broad range of patients an effective treatment option to reduce their risk of cardiovascular and renal disease.

References:

Verma S, Mazer CD, Fitchett D, et al. Empagliflozin reduces mortality and hospitalization for heart failure in patients with type 2 diabetes and peripheral artery disease: a sub-analysis of the EMPA-REG OUTCOME trial. Presented at the 2017 American Heart Association Scientific Sessions, Anaheim, California. November 11-15, 2017. LS-3.

Mahaffey KW, Neal B, Perkovic V, et al. Canagliflozin for primary and secondary prevention of cardiovascular events: results from the CANVAS program [published online November 13, 2017]. Circulation. 2017; doi:10.1161/CIRCULATIONAHA.117.032038.