Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Aug 10:13:940654.
doi: 10.3389/fendo.2022.940654. eCollection 2022.

Effects of sacubitril/valsartan on both metabolic parameters and insulin resistance in prediabetic non-obese patients with heart failure and reduced ejection fraction

Cosima Cloro  1 , Isabella Zaffina  2 , Luca Sacchetta  3 , Federico Arturi  4 , Cristina Clausi  5 , Stefania Lucà  2 , Maria Chiara Pelle  2 , Federica Giofrè  2 , Giuseppe Armentaro  6 , Valentina Forte  2 , Francesco Mario De Rosa  1 , Angela Sciacqua  6 , Franco Arturi  2   7
Affiliations

Effects of sacubitril/valsartan on both metabolic parameters and insulin resistance in prediabetic non-obese patients with heart failure and reduced ejection fraction

Cosima Cloro et al. Front Endocrinol (Lausanne). .

Abstract

Background: The effects of sacubitril/valsartan (sac/val) on metabolic parameters and insulin resistance (IR) in non-obese/prediabetic patients have not been previously described.

Aim: To evaluate the effects of sac/val on glycemic and metabolic parameters, Homeostatic Model Assessment of IR (HOMA-IR), and echocardiographic parameters in prediabetic patients with heart failure with reduced ejection fraction (HFrEF).

Methods: Fifty-nine patients with HFrEF (EF < 35%) but without obesity and/or type 2 diabetes mellitus have been enrolled. All the patients at baseline and week 24 underwent complete anthropometrical evaluation and were subjected to an echocardiogram test. IR has been assessed by HOMA-IR.

Results: After 24-week of treatment with sac/val, a significant reduction in fasting plasma glucose (109 ± 9 vs 103 ± 8 mg/dl, p < 0.0001), fasting plasma insulin (16 ± 4 vs 10 ± 4 UI/L), and hemoglobin A1c (HbA1c) value (6% ± 0.5% vs 5.3% ± 0.3%, p < 0.0001) was observed. Similarly, we observed a significant improvement in IR (HOMA-IR, 4.4 ± 0.9 vs 2.5 ± 0.6, p < 0.0001). The echocardiogram evaluation showed a significant reduction of the left ventricular end-diastolic volume (168 ± 24 vs 158 ± 22 ml, p < 0.05), a significant reduction of the left ventricular end-systolic volume (111 ± 26 vs 98 ± 22 ml, p < 0.005), and a significant reduction of E/e' ratio. Sac/val use was also associated with an average 5.1% increase in ejection fraction.

Conclusions: Our data seem to indicate that sal/val enhances metabolic control and improves insulin resistance also in prediabetic non-obese patients with HFrEF.

Keywords: HFrEF; beta cell; cardiovascular disease; insulin; insulin resistance; prediabetes; sacubitril/valsartan; type 2 diabetes.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Effects of neprilysin inhibition and RAAS inhibition on insulin sensitivity and EF in prediabetic non-obese patients with HFrEF in treatment with sac/val. RAAS, renin–angiotensin–aldosterone system; EF, ejection fraction; HFrEF, heart failure with reduced ejection fraction; sac/val, sacubitril/valsartan.
See this image and copyright information in PMC

References

    1. Savarese G, Lund LH. Global public health burden of heart failure. Card Fail Rev (2017) 3(1):7–11. doi: 10.15420/cfr.2016:25:2 - DOI - PMC - PubMed
    1. Vardeny O, Miller R. Combined neprilysin and renin-angiotensin system inhibition for the treatment of heart failure. JACC Heart Fail (2014) 2(6):663–70. doi: 10.1016/j.jchf.2014.09.001 - DOI - PubMed
    1. McMurray JJ, Packer M. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med (2014) 371(11):993–1004. doi: 10.1056/NEJMoa1409077 - DOI - PubMed
    1. Dunlay SM, Givertz MM. Type 2 diabetes mellitus and heart failure: A scientific statement from the American heart association and the heart failure society of America: This statement does not represent an update of the 2017 ACC/AHA/HFSA heart failure guideline update [published correction appears in circulation. Circulation (2019. 2019) 140(7):e294–324. doi: 10.1161/CIR.0000000000000691 - DOI - PubMed
    1. Pocock SJ, Wang D. Predictors of mortality and morbidity in patients with chronic heart failure. Eur Heart J (2006) 27(1):65–75. doi: 10.1093/eurheartj/ehi555 - DOI - PubMed