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
. 2018 Mar 6;137(10):1060-1073.
doi: 10.1161/CIRCULATIONAHA.117.032099.

Glucose-Lowering Therapies and Heart Failure in Type 2 Diabetes Mellitus: Mechanistic Links, Clinical Data, and Future Directions

Shilpa Vijayakumar  1 , Muthiah Vaduganathan  2 , Javed Butler  3
Affiliations
Review

Glucose-Lowering Therapies and Heart Failure in Type 2 Diabetes Mellitus: Mechanistic Links, Clinical Data, and Future Directions

Shilpa Vijayakumar et al. Circulation. .

Abstract

Diabetes mellitus independently increases the risk of and mortality from heart failure in a manner that is well established but inadequately understood. Glycemic optimization does not eliminate this risk, and measures of glycemic control are insufficient markers of cardiovascular risk. In response to a regulatory guidance from the US Food and Drug Administration, glucose-lowering agents are now routinely evaluated in large cardiovascular outcome trials. These recent trial experiences of novel and established glucose-lowering therapies have shown variable risks and benefits with respect to heart failure. Cardiovascular outcome trials have increasingly included heart failure events as either a component of the primary end point or a secondary adjudicated end point. We comprehensively review each established and novel currently marketed glucose-lowering therapy, their biological targets, mechanisms of action, and relationships with heart failure. We then highlight gaps in available evidence and directions for future research regarding the ascertainment of heart failure-related data in the evaluation of emerging glucose-lowering therapies.

Keywords: clinical trials; diabetes mellitus; heart failure; outcomes.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Glucose-lowering therapies, renal sodium handling, and risks of fluid retention. Therapeutic effects on renal sodium handling are highlighted, but other relevant mechanistic pathways contributing to therapy-related heart failure risks and benefits are not described in this figure. Abbreviations: DPP-4, dipeptidyl peptidase-4; GLP-1, glucagon-like peptide 1; PPAR, peroxisome proliferator-activated receptor; SGLT-2, sodium-glucose cotransporter-2
Figure 2
Figure 2
Spectrum of cardiovascular risk of target patient population of key cardiovascular outcome trials of glucose-lowering therapies. The area of each circle correlates with sample size of each respective study. Abbreviations: CV, cardiovascular; DPP-4, dipeptidyl peptidase-4; GLP-1, glucagon-like peptide 1; PPAR = peroxisome proliferator-activated receptor; SGLT-2, sodium-glucose cotransporter-2
See this image and copyright information in PMC

References

    1. Bertoni AG, Hundley WG, Massing MW, Bonds DE, Burke GL, Goff DC., Jr Heart failure prevalence, incidence, and mortality in the elderly with diabetes. Diabetes Care. 2004;27:699–703. - PubMed
    1. From AM, Leibson CL, Bursi F, Redfield MM, Weston SA, Jacobsen SJ, Rodeheffer RJ, Roger VL. Diabetes in heart failure: prevalence and impact on outcome in the population. Am J Med. 2006;119:591–599. - PubMed
    1. Bauters C, Lamblin N, Mc Fadden EP, Van Belle E, Millaire A, de Groote P. Influence of diabetes mellitus on heart failure risk and outcome. Cardiovasc Diabetol. 2003;2:1. - PMC - PubMed
    1. Kapoor JR, Fonarow GC, Zhao X, Kapoor R, Hernandez AF, Heidenreich PA. Diabetes, quality of care, and in-hospital outcomes in patients hospitalized with heart failure. Am Heart J. 2011;162:480–486. e3. - PubMed
    1. Sarma S, Mentz RJ, Kwasny MJ, Fought AJ, Huffman M, Subacius H, Nodari S, Konstam M, Swedberg K, Maggioni AP, Zannad F, Bonow RO, Gheorghiade M. Association between diabetes mellitus and post-discharge outcomes in patients hospitalized with heart failure: findings from the EVEREST trial. Eur J Heart Fail. 2013;15:194–202. - PMC - PubMed

Publication types

Substances