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

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.

• Authors: 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
• Journal: Cardiovascular diabetology (Cardiovasc Diabetol) Vol. 21 Issue 1 Pg. 110 (06 18 2022) ISSN: 1475-2840 [Electronic] England
• PMID: 35717169 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2022. The Author(s).

Chemical References

• Aminobutyrates
• Angiotensin Receptor Antagonists
• Biphenyl Compounds
• Blood Glucose
• Glycated Hemoglobin A
• Insulins
• Tetrazoles
• sacubitril
• Enalapril
• Valsartan

Topics

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