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

Wijkman, M. O. et al. (2022) Effects of sacubitril/valsartan on glycemia in patients with diabetes and heart failure: the PARAGON-HF and PARADIGM-HF trials. Cardiovascular Diabetology, 21, 110. (doi: 10.1186/s12933-022-01545-1) (PMID:35717169) (PMCID:PMC9206286)

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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

Item Type:Articles
Additional Information:The PARAGON-HF and PARADIGM-HF studies were funded by Novartis. MOW is supported by grants from The Swedish Heart Association, The Swedish Society of Medicine and Region Östergötland, Sweden. JWC has received a National, Heart, Lung, and Blood Institute postdoctoral training grant (T32HL094301). SJS is supported by grants from the National Institutes of Health (R01 HL107577, R01 HL127028, R01 HL140731, and R01 HL149423). JJVM is supported by a British Heart Foundation Centre of Research Excellence Grant (RE/18/6/34217).
Glasgow Author(s) Enlighten ID:Jackson, Dr Alice and McMurray, Professor John
Authors: Wijkman, M. O., Claggett, B., Vaduganathan, M., Cunningham, J. W., Rørth, R., Jackson, A., Packer, M., Zile, M., Rouleau, J., Swedberg, K., Lefkowitz, M., Shah, S. J., Pfeffer, M. A., McMurray, J. J.V., and Solomon, S. D.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
Journal Name:Cardiovascular Diabetology
Publisher:BioMed Central
ISSN (Online):1475-2840
Copyright Holders:Copyright © 2022 The Authors
First Published:First published in Cardiovascular Diabetology 21: 110
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
303944BHF Centre of ExcellenceColin BerryBritish Heart Foundation (BHF)RE/18/6/34217CAMS - Cardiovascular Science