Anti-Diabetic Therapy and Heart Failure: Recent Advances in Clinical Evidence and Molecular Mechanism
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 inhib...
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MDPI AG
2023-04-01
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| Online Access: | https://www.mdpi.com/2075-1729/13/4/1024 |
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| author | Chih-Neng Hsu Chin-Feng Hsuan Daniel Liao Jack Keng-Jui Chang Allen Jiun-Wei Chang Siow-Wey Hee Hsiao-Lin Lee Sean I. F. Teng |
| author_facet | Chih-Neng Hsu Chin-Feng Hsuan Daniel Liao Jack Keng-Jui Chang Allen Jiun-Wei Chang Siow-Wey Hee Hsiao-Lin Lee Sean I. F. Teng |
| author_sort | Chih-Neng Hsu |
| collection | DOAJ |
| description | 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. |
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| institution | Directory Open Access Journal |
| issn | 2075-1729 |
| language | English |
| last_indexed | 2024-03-11T04:50:30Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Life |
| spelling | doaj.art-e520e704a9bf4c87addb7f8947c7e46d2023-11-17T20:07:05ZengMDPI AGLife2075-17292023-04-01134102410.3390/life13041024Anti-Diabetic Therapy and Heart Failure: Recent Advances in Clinical Evidence and Molecular MechanismChih-Neng Hsu0Chin-Feng Hsuan1Daniel Liao2Jack Keng-Jui Chang3Allen Jiun-Wei Chang4Siow-Wey Hee5Hsiao-Lin Lee6Sean I. F. Teng7Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital Yunlin Branch, Yunlin 640, TaiwanDivision of Cardiology, Department of Internal Medicine, E-Da Hospital, I-Shou University, Kaohsiung 824, TaiwanGraduate Institute of Medical Genomics and Proteomics, College of Medicine, National Taiwan University, Taipei 100, TaiwanBiological Programs for Younger Scholar, Academia Sinica, Taipei 115, TaiwanGraduate Institute of Medical Genomics and Proteomics, College of Medicine, National Taiwan University, Taipei 100, TaiwanDepartment of Internal Medicine, National Taiwan University Hospital, Taipei 100, TaiwanGraduate Institute of Medical Genomics and Proteomics, College of Medicine, National Taiwan University, Taipei 100, TaiwanDepartment of Cardiology, Ming-Sheng General Hospital, Taoyuan 330, TaiwanDiabetic 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.https://www.mdpi.com/2075-1729/13/4/1024anti-diabetic therapyheart failurerandomized clinical trialsmolecular mechanismsodium-glucose co-transporter-2 inhibitors |
| spellingShingle | Chih-Neng Hsu Chin-Feng Hsuan Daniel Liao Jack Keng-Jui Chang Allen Jiun-Wei Chang Siow-Wey Hee Hsiao-Lin Lee Sean I. F. Teng Anti-Diabetic Therapy and Heart Failure: Recent Advances in Clinical Evidence and Molecular Mechanism Life anti-diabetic therapy heart failure randomized clinical trials molecular mechanism sodium-glucose co-transporter-2 inhibitors |
| title | Anti-Diabetic Therapy and Heart Failure: Recent Advances in Clinical Evidence and Molecular Mechanism |
| title_full | Anti-Diabetic Therapy and Heart Failure: Recent Advances in Clinical Evidence and Molecular Mechanism |
| title_fullStr | Anti-Diabetic Therapy and Heart Failure: Recent Advances in Clinical Evidence and Molecular Mechanism |
| title_full_unstemmed | Anti-Diabetic Therapy and Heart Failure: Recent Advances in Clinical Evidence and Molecular Mechanism |
| title_short | Anti-Diabetic Therapy and Heart Failure: Recent Advances in Clinical Evidence and Molecular Mechanism |
| title_sort | anti diabetic therapy and heart failure recent advances in clinical evidence and molecular mechanism |
| topic | anti-diabetic therapy heart failure randomized clinical trials molecular mechanism sodium-glucose co-transporter-2 inhibitors |
| url | https://www.mdpi.com/2075-1729/13/4/1024 |
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