Neprilysin inhibition could improve glycemic control in diabetic HF patients
medwireNews: A post-hoc analysis of the PARADIGM-HF trial suggests that the inclusion of a neprilysin inhibitor in the medication of patients with heart failure (HF) and diabetes might enhance glycemic control.
The findings were presented today at the American College of Cardiology conference in Washington, DC, USA, and simultaneously published in The Lancet Diabetes & Endocrinology.
Writing in a linked commentary, Gregory Giamouzis (University of Thessaly, Larissa, Greece) and Javed Butler (Stony Brook University, New York, USA) note that patients with both HF and diabetes have particularly poor outcomes, including in PARADIGM-HF. In addition, several antidiabetic drugs have been associated with worsening HF symptoms and several HF therapies are believed to worsen glycemic control.
“Thus, any heart failure therapy that is protective against incident diabetes or worsening glycaemic control is a welcome addition,” they write.
In total, 3778 (45%) of the 8399 patients with HF and reduced ejection fraction enrolled to PARADIGM-HF also had diabetes. Between screening and the 1-year follow-up, diabetes patients who were randomly assigned to receive sacubitril/valsartan 97 mg/103 mg twice a day had a reduction in glycated hemoglobin from 7.41% to 7.09%. Those assigned to take twice-daily enalapril 10 mg had a reduction from 7.48% to 7.30%, and the absolute difference between the two groups, of 0.13%, was statistically significant.
Over the course of the entire 3-year trial, the absolute difference in the change between the two groups was 0.14%, again significantly favoring the sacubitril/valsartan group.
“[C]linicians should be informed that doses of antihyperglycaemic drugs might need to be adjusted when using sacubitril/valsartan,” say Giamouzis and Butler.
Taking sacubitril/valsartan also appeared to reduce the likelihood of transition to insulin, with this occurring by the 3-year mark in 9.1% of patients taking the combination drug, compared with 13.3% of those taking the angiotensin-converting enzyme inhibitor.
Sacubitril/valsartan had no observable effect on the incidence of new-onset diabetes among patients without it at screening, but these numbers were very small in both treatment groups. There was no difference between the groups in the risk for hypoglycemia; however, body mass index increased slightly but significantly more in patients taking sacubitril/valsartan than those taking enalapril, by an average of 0.28 kg/m2.
Scott Solomon (Brigham and Women’s Hospital, Boston, Massachusetts, USA) and study co-authors suggest that the effect of sacubitril/valsartan on glycemic control “is most likely secondary to the inhibition of neprilysin and consequent modulation of its circulating substrates.”
They say: “These post-hoc findings should be considered hypothesis-generating and should help inform clinicians who will be using sacubitril/valsartan in patients with heart failure.”
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