Anti-Diabetic Therapy and Heart Failure: Recent Advances in Clinical Evidence and Molecular Mechanism

Author:

Hsu Chih-Neng1,Hsuan Chin-Feng234ORCID,Liao Daniel5,Chang Jack Keng-Jui6,Chang Allen Jiun-Wei5,Hee Siow-Wey7,Lee Hsiao-Lin5,Teng Sean I. F.8

Affiliation:

1. Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital Yunlin Branch, Yunlin 640, Taiwan

2. Division of Cardiology, Department of Internal Medicine, E-Da Hospital, I-Shou University, Kaohsiung 824, Taiwan

3. Division of Cardiology, Department of Internal Medicine, E-Da Dachang Hospital, I-Shou University, Kaohsiung 824, Taiwan

4. School of Medicine, College of Medicine, I-Shou University, Kaohsiung 840, Taiwan

5. Graduate Institute of Medical Genomics and Proteomics, College of Medicine, National Taiwan University, Taipei 100, Taiwan

6. Biological Programs for Younger Scholar, Academia Sinica, Taipei 115, Taiwan

7. Department of Internal Medicine, National Taiwan University Hospital, Taipei 100, Taiwan

8. Department of Cardiology, Ming-Sheng General Hospital, Taoyuan 330, Taiwan

Abstract

Diabetic patients have a two- to four-fold increase in the risk of heart failure (HF), and the co-existence of diabetes and HF is associated with poor prognosis. In randomized clinical trials (RCTs), compelling evidence has demonstrated the beneficial effects of sodium-glucose co-transporter-2 inhibitors on HF. The mechanism includes increased glucosuria, restored tubular glomerular feedback with attenuated renin–angiotensin II–aldosterone activation, improved energy utilization, decreased sympathetic tone, improved mitochondria calcium homeostasis, enhanced autophagy, and reduced cardiac inflammation, oxidative stress, and fibrosis. The RCTs demonstrated a neutral effect of the glucagon-like peptide receptor agonist on HF despite its weight-reducing effect, probably due to it possibly increasing the heart rate via increasing cyclic adenosine monophosphate (cAMP). Observational studies supported the markedly beneficial effects of bariatric and metabolic surgery on HF despite no current supporting evidence from RCTs. Bromocriptine can be used to treat peripartum cardiomyopathy by reducing the harmful cleaved prolactin fragments during late pregnancy. Preclinical studies suggest the possible beneficial effect of imeglimin on HF through improving mitochondrial function, but further clinical evidence is needed. Although abundant preclinical and observational studies support the beneficial effects of metformin on HF, there is limited evidence from RCTs. Thiazolidinediones increase the risk of hospitalized HF through increasing renal tubular sodium reabsorption mediated via both the genomic and non-genomic action of PPARγ. RCTs suggest that dipeptidyl peptidase-4 inhibitors, including saxagliptin and possibly alogliptin, may increase the risk of hospitalized HF, probably owing to increased circulating vasoactive peptides, which impair endothelial function, activate sympathetic tones, and cause cardiac remodeling. Observational studies and RCTs have demonstrated the neutral effects of insulin, sulfonylureas, an alpha-glucosidase inhibitor, and lifestyle interventions on HF in diabetic patients.

Funder

Joint Study Program of National Taiwan University Hospital and Ming-Sheng General Hospital

National Taiwan University Hospital Yunlin branch

Joint Study Program of National Taiwan University Hospital and E-Da Hospital

Publisher

MDPI AG

Subject

Paleontology,Space and Planetary Science,General Biochemistry, Genetics and Molecular Biology,Ecology, Evolution, Behavior and Systematics

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