Sodium-glucose co-transporter 2 inhibitors in heart failure: an updated evidence-based practical guidance for clinicians

Monzo, Luca; Ferrari, Ilaria; Cicogna, F; Tota, Claudia; Cice, Gennaro; Girerd, Nicolas; Calò, Leonardo

doi:10.1093/eurheartjsupp/suad055

Cited by 6 publications

(3 citation statements)

References 46 publications

(67 reference statements)

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“…Moreover, SGLT2is have antioxidative effects, improve mitochondrial function, provide a favorable metabolic shift towards fatty acids and ketone bodies rather than glucose in myocytes, stimulate erythropoiesis, attenuate the sympathetic tone [ 164 ], insulin resistance, and systemic inflammation [ 165 ]. These effects ameliorate cardiac pump efficiency and improve long-term outcomes related to chronic heart failure, regardless of hyperglycemia and background cardiac pump efficiency [ 166 ]. SGLT2is affect body composition by specifically reducing both fat and fat-free mass [ 167 ].…”

Section: Preventing Sarcopenia: a Therapeutic Target In Primary And S...mentioning

confidence: 99%

Sarcopenia and Diabetes: A Detrimental Liaison of Advancing Age

Lisco,

Disoteo,

De Tullio

et al. 2023

Nutrients

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Sarcopenia is an age-related clinical complaint characterized by the progressive deterioration of skeletal muscle mass and strength over time. Type 2 diabetes (T2D) is associated with faster and more relevant skeletal muscle impairment. Both conditions influence each other, leading to negative consequences on glycemic control, cardiovascular risk, general health status, risk of falls, frailty, overall quality of life, and mortality. PubMed/Medline, Scopus, Web of Science, and Google Scholar were searched for research articles, scientific reports, observational studies, clinical trials, narrative and systematic reviews, and meta-analyses to review the evidence on the pathophysiology of di-abetes-induced sarcopenia, its relevance in terms of glucose control and diabetes-related outcomes, and diagnostic and therapeutic challenges. The review comprehensively addresses key elements for the clinical definition and diagnostic criteria of sarcopenia, the pathophysiological correlation be-tween T2D, sarcopenia, and related outcomes, a critical review of the role of antihyperglycemic treatment on skeletal muscle health, and perspectives on the role of specific treatment targeting myokine signaling pathways involved in glucose control and the regulation of skeletal muscle metabolism and trophism. Prompt diagnosis and adequate management, including lifestyle inter-vention, health diet programs, micronutrient supplementation, physical exercise, and pharmaco-logical treatment, are needed to prevent or delay skeletal muscle deterioration in T2D.

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Section: Preventing Sarcopenia: a Therapeutic Target In Primary And S...mentioning

confidence: 99%

Sarcopenia and Diabetes: A Detrimental Liaison of Advancing Age

Lisco,

Disoteo,

De Tullio

et al. 2023

Nutrients

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show abstract

“…Importantly, multicenter studies and meta-analyses confirmed that SGLT2 inhibitors also reduce the risk of CV outcome in patients without diabetes [59][60][61]. Given these reports, clinical practice guidelines now recommend the use of SGLT2 inhibitors in patients with heart failure across the spectrum of ejection fraction and in combination with various other drugs [13,62].…”

Section: Pleiotropic Effects Of Sglt2 Inhibitorsmentioning

confidence: 97%

SGLT2 Inhibitors in Kidney Diseases—A Narrative Review

Gajewska,

Wasiak,

Sapeda

et al. 2024

IJMS

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Some of the most common conditions affecting people are kidney diseases. Among them, we distinguish chronic kidney disease and acute kidney injury. Both entities pose serious health risks, so new drugs are still being sought to treat and prevent them. In recent years, such a role has begun to be assigned to sodium-glucose cotransporter-2 (SGLT2) inhibitors. They increase the amount of glucose excreted in the urine. For this reason, they are currently used as a first-line drug in type 2 diabetes mellitus. Due to their demonstrated cardioprotective effect, they are also used in heart failure treatment. As for the renal effects of SGLT2 inhibitors, they reduce intraglomerular pressure and decrease albuminuria. This results in a slower decline in glomelular filtration rate (GFR) in patients with kidney disease. In addition, these drugs have anti-inflammatory and antifibrotic effects. In the following article, we review the evidence for the effectiveness of this group of drugs in kidney disease and their nephroprotective effect. Further research is still needed, but meta-analyses indicate SGLT2 inhibitors' efficacy in kidney disease, especially the one caused by diabetes. Development of new drugs and clinical trials on specific patient subgroups will further refine their nephroprotective effects.

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“…However, unlike sodium-glucose co-transporter 2 (SGLT2) inhibitors [ 7 ], evidence of a benefit for GLP-1 RAs in heart failure (HF) is controversial and remains to be fully established in dedicated studies [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

Evidence that tirzepatide protects against diabetes-related cardiac damages

Taktaz,

Scisciola,

Fontanella

et al. 2024

Cardiovasc Diabetol

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Background Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are effective antidiabetic drugs with potential cardiovascular benefits. Despite their well-established role in reducing the risk of major adverse cardiovascular events (MACE), their impact on heart failure (HF) remains unclear. Therefore, our study examined the cardioprotective effects of tirzepatide (TZT), a novel glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) receptor agonist. Methods A three-steps approach was designed: (i) Meta-analysis investigation with the primary objective of assessing major adverse cardiovascular events (MACE) occurrence from major randomized clinical trials.; (ii) TZT effects on a human cardiac AC16 cell line exposed to normal (5 mM) and high (33 mM) glucose concentrations for 7 days. The gene expression and protein levels of primary markers related to cardiac fibrosis, hypertrophy, and calcium modulation were evaluated. (iii) In silico data from bioinformatic analyses for generating an interaction map that delineates the potential mechanism of action of TZT. Results Meta-analysis showed a reduced risk for MACE events by TZT therapy (HR was 0.59 (95% CI 0.40–0.79, Heterogeneity: r2 = 0.01, I2 = 23.45%, H2 = 1.31). In the human AC16 cardiac cell line treatment with 100 nM TZT contrasted high glucose (HG) levels increase in the expression of markers associated with fibrosis, hypertrophy, and cell death (p < 0.05 for all investigated markers). Bioinformatics analysis confirmed the interaction between the analyzed markers and the associated pathways found in AC16 cells by which TZT affects apoptosis, fibrosis, and contractility, thus reducing the risk of heart failure. Conclusion Our findings indicate that TZT has beneficial effects on cardiac cells by positively modulating cardiomyocyte death, fibrosis, and hypertrophy in the presence of high glucose concentrations. This suggests that TZT may reduce the risk of diabetes-related cardiac damage, highlighting its potential as a therapeutic option for heart failure management clinical trials. Our study strongly supports the rationale behind the clinical trials currently underway, the results of which will be further investigated to gain insights into the cardiovascular safety and efficacy of TZT. Graphical Abstract

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Sodium-glucose co-transporter 2 inhibitors in heart failure: an updated evidence-based practical guidance for clinicians

Cited by 6 publications

References 46 publications

Sarcopenia and Diabetes: A Detrimental Liaison of Advancing Age

Sarcopenia and Diabetes: A Detrimental Liaison of Advancing Age

SGLT2 Inhibitors in Kidney Diseases—A Narrative Review

Evidence that tirzepatide protects against diabetes-related cardiac damages

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