Effects of sacubitril/valsartan on glycemia in patients with diabetes and heart failure: the PARAGON-HF and PARADIGM-HF trials

Magnus O Wijkman, Brian Claggett, Muthiah Vaduganathan, Jonathan W Cunningham, Rasmus Rørth, Alice Jackson, Milton Packer, Michael Zile, Jean Rouleau, Karl Swedberg, Martin Lefkowitz, Sanjiv J Shah, Marc A Pfeffer, John J V McMurray, Scott D Solomon

27 Citations (Scopus)

Abstract

BACKGROUND: Compared with enalapril, sacubitril/valsartan lowered HbA1c and reduced new insulin therapy in patients with heart failure with reduced ejection fraction (HFrEF) and diabetes in the PARADIGM-HF trial. We sought to assess the glycemic effects of sacubitril/valsartan in heart failure with preserved ejection fraction (HFpEF) and diabetes, and across the spectrum of left ventricular ejection fraction (LVEF) in heart failure and diabetes.

METHODS: We compared the effect of sacubitril/valsartan, relative to valsartan, on HbA1c, new insulin therapy and hypoglycemia in the randomized controlled trial PARAGON-HF, and performed pooled analyses of PARAGON-HF and PARADIGM-HF.

RESULTS: Among 2395 patients with HFpEF and diabetes in PARAGON-HF, sacubitril/valsartan compared with valsartan reduced HbA1c (baseline-adjusted between-group difference in HbA1c change at 48 weeks: - 0.24%, 95% CI - 0.33 to - 0.16%, P < 0.001). Numerically, new insulin treatment was initiated less often in the sacubitril/valsartan group than in the valsartan group, but the difference was not statistically significant (12.8% vs. 16.1%; HR: 0.80, 95% CI 0.62-1.02, P = 0.07). Hypoglycemia adverse event reports were low, but more frequent in those receiving sacubitril/valsartan than in the valsartan group (4.2% vs. 2.6%; HR: 1.64, 95% CI 1.05-2.56, P = 0.030). In a pooled analysis of PARAGON-HF and PARADIGM-HF, the effect of sacubitril/valsartan on change in HbA1c was not significantly modified by LVEF (Pinteraction = 0.56). Across the spectrum of LVEF, sacubitril/valsartan reduced new insulin therapy (HR: 0.75, 95% CI 0.63-0.89, P = 0.001), compared with enalapril or valsartan.

CONCLUSIONS: Sacubitril/valsartan reduced HbA1c and new insulin therapy in patients with heart failure and diabetes across the spectrum of LVEF but may be associated with a slightly higher risk for hypoglycemia. Trial registration ClinicalTrials.gov NCT01920711.

Original languageEnglish
Article number110
JournalCardiovascular Diabetology
Volume21
Issue number1
ISSN1475-2840
DOIs
Publication statusPublished - 18 Jun 2022

Keywords

  • Aminobutyrates/adverse effects
  • Angiotensin Receptor Antagonists/adverse effects
  • Biphenyl Compounds/adverse effects
  • Blood Glucose
  • Diabetes Mellitus/chemically induced
  • Enalapril/adverse effects
  • Glycated Hemoglobin A
  • Heart Failure/chemically induced
  • Humans
  • Hypoglycemia/chemically induced
  • Insulins/pharmacology
  • Stroke Volume
  • Tetrazoles/adverse effects
  • Valsartan/adverse effects
  • Ventricular Function, Left

Fingerprint

Dive into the research topics of 'Effects of sacubitril/valsartan on glycemia in patients with diabetes and heart failure: the PARAGON-HF and PARADIGM-HF trials'. Together they form a unique fingerprint.

Cite this