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
Review
. 2023 Feb 10;13(2):497.
doi: 10.3390/life13020497.

Diabetes Mellitus and Heart Failure: Epidemiology, Pathophysiologic Mechanisms, and the Role of SGLT2 Inhibitors

Panagiotis Theofilis  1 , Evangelos Oikonomou  2 , Konstantinos Tsioufis  1 , Dimitris Tousoulis  1
Affiliations
Review

Diabetes Mellitus and Heart Failure: Epidemiology, Pathophysiologic Mechanisms, and the Role of SGLT2 Inhibitors

Panagiotis Theofilis et al. Life (Basel). .

Abstract

Diabetes mellitus (DM) and heart failure (HF) are frequently encountered afflictions that are linked by a common pathophysiologic background. According to landmark studies, those conditions frequently coexist, and this interaction represents a poor prognostic indicator. Based on mechanistic studies, HF can be propagated by multiple pathophysiologic pathways, such as inflammation, oxidative stress, endothelial dysfunction, fibrosis, cardiac autonomic neuropathy, and alterations in substrate utilization. In this regard, DM may augment myocardial inflammation, fibrosis, autonomic dysfunction, and lipotoxicity. As the interaction between DM and HF appears critical, the new cornerstone in DM and HF treatment, sodium-glucose cotransporter-2 inhibitors (SGLT2i), may be able to revert the pathophysiology of those conditions and lead to beneficial HF outcomes. In this review, we aim to highlight the deleterious pathophysiologic interaction between DM and HF, as well as demonstrate the beneficial role of SGLT2i in this field.

Keywords: SGLT2 inhibitors; diabetes mellitus; heart failure.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Impaired autophagy in heart failure and the potential role of SGLT2 inhibition. (A) Heart failure is a nutrient excess disease that promotes the buildup of lipid and glucose intermediates in cardiomyocytes, resulting in defective autophagy, apoptosis, oxidative (OX) and endoplasmic reticulum (ER) stress, and inflammation. (B) SGLT2 inhibitors trigger a state of apparent nutritional shortage by altering the equilibrium between the Sirtuin-1/Hypoxia-inducible factor (HIF)/AMPK pathway and the Akt/mammalian target of rapamycin complex 1 (mTORC1) pathway. As a result, restoring autophagy benefits the reversal of unfavorable cardiac remodeling. ↑ indicates an increase, ↓ indicates a decrease.
Figure 2
Figure 2
Timeline of landmark SGLT2 inhibitor randomized clinical trials. Yellow indicates cardiovascular outcome trials, red indicates trials among heart failure populations, and blue indicates trials among chronic kidney disease populations.
See this image and copyright information in PMC

References

    1. Saeedi P., Petersohn I., Salpea P., Malanda B., Karuranga S., Unwin N., Colagiuri S., Guariguata L., Motala A.A., Ogurtsova K., et al. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9(th) edition. Diabetes Res. Clin. Pract. 2019;157:107843. doi: 10.1016/j.diabres.2019.107843. - DOI - PubMed
    1. Ling W., Huang Y., Huang Y.M., Fan R.R., Sui Y., Zhao H.L. Global trend of diabetes mortality attributed to vascular complications, 2000-2016. Cardiovasc. Diabetol. 2020;19:182. doi: 10.1186/s12933-020-01159-5. - DOI - PMC - PubMed
    1. Einarson T.R., Acs A., Ludwig C., Panton U.H. Prevalence of cardiovascular disease in type 2 diabetes: A systematic literature review of scientific evidence from across the world in 2007–2017. Cardiovasc. Diabetol. 2018;17:83. doi: 10.1186/s12933-018-0728-6. - DOI - PMC - PubMed
    1. McAllister D.A., Read S.H., Kerssens J., Livingstone S., McGurnaghan S., Jhund P., Petrie J., Sattar N., Fischbacher C., Kristensen S.L., et al. Incidence of Hospitalization for Heart Failure and Case-Fatality Among 3.25 Million People With and Without Diabetes Mellitus. Circulation. 2018;138:2774–2786. doi: 10.1161/CIRCULATIONAHA.118.034986. - DOI - PMC - PubMed
    1. Ciardullo S., Cannistraci R., Mazzetti S., Mortara A., Perseghin G. Twenty-year trends in heart failure among U.S. adults, 1999–2018: The growing impact of obesity and diabetes. Int. J. Cardiol. 2022;362:104–109. doi: 10.1016/j.ijcard.2022.02.037. - DOI - PubMed