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New Insights of Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors in Biomedical...
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New Insights of Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors in Biomedical Applications

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Pharmacology".

Deadline for manuscript submissions: 30 November 2025 | Viewed by 5484

Special Issue Editors

Dr. Afif Nakhleh

E-Mail Website
Guest Editor
Institute of Endocrinology, Diabetes and Metabolism, Rambam Health Care Campus, Haifa 3109601, Israel
Interests: real-world studies in diabetes and chronic kidney disease; novel therapeutic approaches for diabetes. pituitary and adrenal disorders
Dr. Bshara Mansour

E-Mail Website
Guest Editor
Maccabi Healthcare Services, Haifa 3508510, Israel
Interests: genetic diseases of kidney (nephrotic syndrome); SGLT2 inhibitors and proteinuria; SGLT2 inhibitors/GLP1 receptor agonists and their effect on tubuloglomerular feedback and renal autoregulation
Prof. Dr. Naim Shehadeh

E-Mail Website
Guest Editor
Faculty of Medicine, Bar Ilan University, Ramat Gan 5290002, Israel
Interests: treatment and prevention of complications in type 2 diabetes; pathogenesis and prevention of type 1 diabetes, and the effect of orally administered insulin on the digestive system; education programs for a healthy lifestyle and access to health services for disadvantaged peripheral populations

Special Issue Information

Dear Colleagues，

Sodium–glucose cotransporter 2 (SGLT2) inhibitors have emerged as a promising class of medications with significant therapeutic potential extending beyond glycemic control in diabetes management. This Special Issue of Pharmaceuticals welcomes research articles that investigate the pleiotropic effects of SGLT2 inhibitors across a wide spectrum of metabolic, renal, and cardiovascular diseases, aiming to elucidate their potential therapeutic benefits and contribute to the development of novel treatment strategies.

As the research landscape continues to evolve, propelled by ongoing clinical trials and extensive mechanistic studies, this Special Issue seeks to foster collaboration, information exchange, and meaningful dialog among researchers in the field. We strongly encourage the submission of original research articles, comprehensive reviews, and thought-provoking perspective papers that shed light on the pharmacological properties of SGLT2 inhibitors. This includes an in-depth exploration of their mechanisms of action, clinical efficacy, promising new therapeutic applications, and any innovative findings that showcase and tackle the challenges and future directions in SGLT2 inhibitor research.

We look forward to your valuable contribution.

Dr. Afif Nakhleh
Dr. Bshara Mansour
Prof. Dr. Naim Shehadeh
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceuticals is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • SGLT2 Inhibitors
  • cardiovascular protection
  • renal health
  • metabolic benefits

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Published Papers (3 papers)

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Review

28 pages, 727 KiB  
Review
Potential New Applications of Sodium–Glucose Cotransporter-2 Inhibitors Across the Continuum of Cancer-Related Cardiovascular Toxicity
by Agnieszka Maria Zebrowska and Anna Borowiec
Pharmaceuticals 2025, 18(6), 857; https://doi.org/10.3390/ph18060857 - 9 Jun 2025
Viewed by 725
Abstract
Sodium–glucose cotransporter-2 inhibitors (SGLT2i), initially developed for the management of type 2 diabetes mellitus, have demonstrated significant nephroprotective and cardioprotective effects. These benefits have led to their inclusion in heart failure (HF) management guidelines, irrespective of glycemic status and left ventricular ejection fraction [...] Read more.
Sodium–glucose cotransporter-2 inhibitors (SGLT2i), initially developed for the management of type 2 diabetes mellitus, have demonstrated significant nephroprotective and cardioprotective effects. These benefits have led to their inclusion in heart failure (HF) management guidelines, irrespective of glycemic status and left ventricular ejection fraction (LVEF). Various anticancer therapies, particularly anthracyclines, are associated with substantial cardiotoxicity risks, resulting in cancer therapy-related cardiovascular toxicity (CTR-CVT). Promising evidence from preclinical and observational studies indicates that SGLT2i may mitigate cardiotoxic effects of cancer therapy by alleviating LVEF decline, reducing HF incidence and hospitalizations, and lowering overall mortality. Moreover, improved survival has been reported in patients with various malignancies. The current review explores the potential applications of SGLT2i in the prevention of CTR-CVT, highlights their possible mechanisms of cardioprotection, discusses the published evidence, and emphasizes the need for the results from ongoing randomized controlled trials to establish SGLT2i efficacy and safety in cardio-oncology patients. Full article
(This article belongs to the Special Issue New Insights of Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors in Biomedical Applications)
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26 pages, 1707 KiB  
Review
Doxorubicin-Induced Cardiotoxicity and the Emerging Role of SGLT2 Inhibitors: From Glycemic Control to Cardio-Oncology
by Iacob-Daniel Goje, Greta-Ionela Goje, Valentin Laurențiu Ordodi, Valentina Gabriela Ciobotaru, Vlad Sabin Ivan, Roxana Buzaș, Oana Tunea, Florina Bojin and Daniel-Florin Lighezan
Pharmaceuticals 2025, 18(5), 681; https://doi.org/10.3390/ph18050681 - 3 May 2025
Cited by 1 | Viewed by 2282
Abstract
Cancer remains the second leading cause of death worldwide. Doxorubicin (DOX) is a cornerstone of hematologic malignancy treatment, but it is limited by its dose-dependent cardiotoxicity, leading to systolic and diastolic cardiac dysfunction and, ultimately, dilated hypokinetic cardiomyopathy. Cardio-oncology has emerged as a [...] Read more.
Cancer remains the second leading cause of death worldwide. Doxorubicin (DOX) is a cornerstone of hematologic malignancy treatment, but it is limited by its dose-dependent cardiotoxicity, leading to systolic and diastolic cardiac dysfunction and, ultimately, dilated hypokinetic cardiomyopathy. Cardio-oncology has emerged as a subspecialty addressing cardiovascular complications in cancer patients, highlighting preventive and therapeutic strategies to reduce cancer therapy-related cardiac dysfunction (CTRCD). Current approaches, including beta-blockers, renin–angiotensin system (RAS) inhibitors, and statins, offer partial cardioprotection. Sodium-glucose cotransporter-2 (SGLT2) inhibitors, initially developed for type 2 diabetes mellitus (T2DM), demonstrate pleiotropic cardioprotective effects beyond glycemic control, including reduced oxidative stress, inflammation, and myocardial remodeling. This review explores the interplay between anthracycline therapy, particularly DOX, and cardiotoxicity while evaluating SGLT2 inhibitors as novel agents in cardio-oncology. Preclinical studies suggest SGLT2 inhibitors attenuate CTRCD by preserving mitochondrial function and inhibiting apoptosis, while clinical trials highlight their efficacy in reducing heart failure (HF) hospitalizations and cardiovascular (CV) mortality. Integrating SGLT2 inhibitors into cardio-oncology protocols could revolutionize the management of CTRCD, enhancing patient outcomes in oncology and cardiovascular care. Considering the emerging evidence, SGLT2 inhibitors may provide significant benefits to patients undergoing anthracycline therapy, particularly those with elevated cardiovascular risk profiles. We recommend that future prospective, large-scale clinical trials further evaluate the efficacy and safety of these agents as cardioprotective therapy to optimize individualized treatment strategies. Full article
(This article belongs to the Special Issue New Insights of Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors in Biomedical Applications)
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13 pages, 903 KiB  
Review
Cardiac Fibrosis: Mechanistic Discoveries Linked to SGLT2 Inhibitors
by Filip Rolski and Michał Mączewski
Pharmaceuticals 2025, 18(3), 313; https://doi.org/10.3390/ph18030313 - 24 Feb 2025
Cited by 1 | Viewed by 1728
Abstract
Sodium-glucose cotransporter 2 inhibitors (SGLT2is), commonly known as flozins, have garnered attention not only for their glucose-lowering effects in type 2 diabetes mellitus (T2DM) but also for their cardioprotective properties. This review examines the mechanisms underlying the anti-fibrotic effects of SGLT2is, with a [...] Read more.
Sodium-glucose cotransporter 2 inhibitors (SGLT2is), commonly known as flozins, have garnered attention not only for their glucose-lowering effects in type 2 diabetes mellitus (T2DM) but also for their cardioprotective properties. This review examines the mechanisms underlying the anti-fibrotic effects of SGLT2is, with a focus on key clinical trials and preclinical models. SGLT2is, mainly empagliflozin and dapagliflozin, have demonstrated significant reductions in heart failure-related hospitalizations, cardiovascular death, and fibrosis markers, independent of their glucose-lowering effects. The cardioprotective benefits appear to stem from direct actions on cardiac tissues, modulation of inflammatory responses, and improvements in metabolic parameters. In animal models of heart failure, SGLT2is were demonstrated to reduce cardiac fibrosis through mechanisms involving AMPK activation, reduced oxidative stress, and inhibition of pro-fibrotic pathways, not only through the inhibition of SGLT2 present on cardiac cells but also by targeting several other molecular targets. These findings confirm their efficacy in the treatment of heart failure and align with evidence from human trials, supporting the potential involvement of multiple pathways in mediating cardiac fibrosis. These results also provide a promising basis for clinical trials specifically targeting pathways shared with SGLT2is. Full article
(This article belongs to the Special Issue New Insights of Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors in Biomedical Applications)
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