The influence of anti-hyperglycemic drug therapy on cardiovascular and heart failure outcomes in patients with type 2 diabetes mellitus

Asleh, Rabea; Sheikh‐Ahmad, Mohammad; Briasoulis, Αlexandros; Kushwaha, Sudhir S.

doi:10.1007/s10741-017-9666-8

Cited by 9 publications

(6 citation statements)

References 95 publications

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“…The results of the primary outcome were driven by a reduction in non-fatal MI and stroke. However, in light of its smaller non-inferiority design, this trial may underestimate the difference in CV mortality compared with the much larger LEADER trial ( Asleh et al, 2018 ).…”

Section: Current Therapies: Novel Glucose-lowering Drugsmentioning

confidence: 99%

Diabetic Cardiomyopathy: Current and Future Therapies. Beyond Glycemic Control

et al. 2018

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Diabetes mellitus and the associated complications represent a global burden on human health and economics. Cardiovascular diseases are the leading cause of death in diabetic patients, who have a 2–5 times higher risk of developing heart failure than age-matched non-diabetic patients, independent of other comorbidities. Diabetic cardiomyopathy is defined as the presence of abnormal cardiac structure and performance in the absence of other cardiac risk factors, such coronary artery disease, hypertension, and significant valvular disease. Hyperglycemia, hyperinsulinemia, and insulin resistance mediate the pathological remodeling of the heart, characterized by left ventricle concentric hypertrophy and perivascular and interstitial fibrosis leading to diastolic dysfunction. A change in the metabolic status, impaired calcium homeostasis and energy production, increased inflammation and oxidative stress, as well as an accumulation of advanced glycation end products are among the mechanisms implicated in the pathogenesis of diabetic cardiomyopathy. Despite a growing interest in the pathophysiology of diabetic cardiomyopathy, there are no specific guidelines for diagnosing patients or structuring a treatment strategy in clinical practice. Anti-hyperglycemic drugs are crucial in the management of diabetes by effectively reducing microvascular complications, preventing renal failure, retinopathy, and nerve damage. Interestingly, several drugs currently in use can improve cardiac health beyond their ability to control glycemia. GLP-1 receptor agonists and sodium-glucose co-transporter 2 inhibitors have been shown to have a beneficial effect on the cardiovascular system through a direct effect on myocardium, beyond their ability to lower blood glucose levels. In recent years, great improvements have been made toward the possibility of modulating the expression of specific cardiac genes or non-coding RNAs in vivo for therapeutic purpose, opening up the possibility to regulate the expression of key players in the development/progression of diabetic cardiomyopathy. This review summarizes the pathogenesis of diabetic cardiomyopathy, with particular focus on structural and molecular abnormalities occurring during its progression, as well as both current and potential future therapies.

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Section: Current Therapies: Novel Glucose-lowering Drugsmentioning

confidence: 99%

Diabetic Cardiomyopathy: Current and Future Therapies. Beyond Glycemic Control

et al. 2018

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“…Sulphonylureas have a higher incidence of cardiovascular adverse events compared to other hypoglycemic agents, and insulin sensitizers also significantly increase the risk of HF in T2DM patients. 63,64 Recently, SGLT2 inhibitors and GLP-1 agonists have been reported to have a significant reduction in cardiovascular mortality. [65][66][67] A growing number of studies have also shown that SGLT1 inhibition does have cardiovascular benefits.…”

Section: The Effects Of Sglt1 Inhibition On Diabetes-related Heart In...mentioning

confidence: 99%

SGLT1: A Potential Drug Target for Cardiovascular Disease

Zhao¹,

Li²,

Zhou³

2023

DDDT

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SGLT1 and SGLT2 are the two main members of the sodium-glucose cotransporters (SGLTs), which are mainly responsible for glucose reabsorption in the body. In recent years, many large clinical trials have shown that SGLT2 inhibitors have cardiovascular protection for diabetic and non-diabetic patients independent of lowering blood glucose. However, SGLT2 was barely detected in the hearts of humans and animals, while SGLT1 was highly expressed in myocardium. As SGLT2 inhibitors also have a moderate inhibitory effect on SGLT1, the cardiovascular protection of SGLT2 inhibitors may be due to SGLT1 inhibition. SGLT1 expression is associated with pathological processes such as cardiac oxidative stress, inflammation, fibrosis, and cell apoptosis, as well as mitochondrial dysfunction. The purpose of this review is to summarize the protective effects of SGLT1 inhibition on hearts in various cell types, including cardiomyocytes, endothelial cells, and fibroblasts in preclinical studies, and to highlight the underlying molecular mechanisms of protection against cardiovascular diseases. Selective SGLT1 inhibitors could be considered a class of drugs for cardiac-specific therapy in the future.

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“…The risk of heart failure in T2DM remains higher compared to non-DM (diabetes mellitus) individuals after adjustment for other risk factors such as serum cholesterol levels, hypertension, or coronary artery disease [ 50 , 51 ]. On the other hand, the presence of DM worsens prognosis in the heart failure population in which the mortality rates are significantly higher than in the non-DM population [ 52 ].…”

Section: Diabetic Cardiomyopathymentioning

confidence: 99%

Metabolic Effects of Metformin in the Failing Heart

Dziubak

Wójcicka

Wojtak

et al. 2018

IJMS

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Accumulating evidence shows that metformin is an insulin-sensitizing antidiabetic drug widely used in the treatment of type 2 diabetes mellitus (T2DM), which can exert favorable effects on cardiovascular risk and may be safely used in patients with heart failure (HF), and even able to reduce the incidence of HF and to reduce HF mortality. In failing hearts, metformin improves myocardial energy metabolic status through the activation of AMP (adenosine monophosphate)-activated protein kinase (AMPK) and the regulation of lipid and glucose metabolism. By increasing nitric oxide (NO) bioavailability, limiting interstitial fibrosis, reducing the deposition of advanced glycation end-products (AGEs), and inhibiting myocardial cell apoptosis metformin reduces cardiac remodeling and hypertrophy, and thereby preserves left ventricular systolic and diastolic functions. While a lot of preclinical and clinical studies showed the cardiovascular safety of metformin therapy in diabetic patients and HF, to confirm observed benefits, the specific large-scale trials configured for HF development in diabetic patients as a primary endpoints are necessary.

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The influence of anti-hyperglycemic drug therapy on cardiovascular and heart failure outcomes in patients with type 2 diabetes mellitus

Cited by 9 publications

References 95 publications

Diabetic Cardiomyopathy: Current and Future Therapies. Beyond Glycemic Control

Diabetic Cardiomyopathy: Current and Future Therapies. Beyond Glycemic Control

SGLT1: A Potential Drug Target for Cardiovascular Disease

Metabolic Effects of Metformin in the Failing Heart

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