Effects of sodium-glucose cotransporter 2 inhibitors in patients with cancer and diabetes mellitus: a systematic review and meta-analysis Giuseppina Novo, Cristina Madaudo, Antonio Cannatà, Pietro Ameri, Daniela Di Lisi, et al. European Heart Journal Cardiovascular Pharmacotherapy, 2025 Aims Cardiovascular disease and cancer represent significant global health challenges. An overlap between oncology and cardiology is compounded by cancer therapies, which are known to have cardiotoxic effects. Sodium–glucose cotransporter 2 inhibitors (SGLT2i), initially developed for treating diabetes, have shown promising cardiovascular benefits in non-cancer populations, particularly in preventing heart failure (HF) and reducing HF-related hospitalization and mortality in large randomized controlled trials (RCTs) across the spectrum of left ventricular ejection fraction. However, their potential cardioprotective role in cancer patients remains unclear. This systematic review and meta-analysis evaluated cardiovascular outcomes in cancer patients with type 2 diabetes undergoing chemotherapy with concomitant use of SGLT2i compared with those not using SGLT2i. Subgroup analyses were performed to explore patients without baseline HF and patients treated exclusively with anthracyclines. Methods and results A systematic review identified 11 observational retrospective studies (n = 104 327 patients). Based on the National Institutes of Health Quality Assessment Tool checklist, two studies were at moderate risk of bias, while all other included studies had a low risk of bias. Meta-analysis indicated that the use of SGLT2i was associated with a significant reduction in all-cause mortality [0.47, 95% confidence interval (CI) 0.33–0.67, P < 0.0001] and risk of HF hospitalization (0.44, 95% CI 0.27–0.72, P = 0.001). Conclusion The use of SGLT2i may be associated with a significant reduction in all-cause mortality and risk of HF hospitalization in actively treated cancer patients with Type 2 diabetes. Our study highlights the need for further investigation through prospective RCTs to confirm the efficacy and safety of SGLT2i in attenuating cardiotoxicity and supporting cardiovascular health in oncology settings.
Advances in Bruton tyrosine kinase (Btk) inhibition are steered by Bruton tyrosine kinase phylogeny Giorgio Minotti, Massimiliano Camilli, Emanuela Salvatorelli, Pierantonio Menna British Journal of Pharmacology, 2025 Bruton tyrosine kinase (Btk) has long been known to play a key role in chronic lymphatic leukaemia, Waldenström macroglobulinaemia and other B‐cell proliferative disorders. An impressive programme of drug discovery and clinical development led to the approval of covalent and non‐covalent Btk inhibitors that became pillars of treatment of such malignancies. However, both a risk of cardiovascular events and the emergence of an elusive mutational landscape seem to complicate the clinical use of each Btk inhibitor. In this plain language mini‐review, we show that the search for better Btk inhibitors is challenged by the ancestral origin of Btk, its homology with innocent kinases in cardiovascular system and unique phylogenetic‐like modalities with which Btk can mutate upon exposure to one inhibitor or another. Whereas basic and clinical pharmacology is already at work to explore new avenues of Btk inhibition, phylogeny remains behind the curtain to steer achievements and failures in this field.
Sodium–glucose cotransporter 2 inhibitors and the cancer patient: from diabetes to cardioprotection and beyond Massimiliano Camilli, Marcello Viscovo, Luca Maggio, Alice Bonanni, Ilaria Torre, et al. Basic Research in Cardiology, 2025 Sodium–glucose cotransporter 2 inhibitors (SGLT2i), a new drug class initially designed and approved for treatment of diabetes mellitus, have been shown to exert pleiotropic metabolic and direct cardioprotective and nephroprotective effects that extend beyond their glucose-lowering action. These properties prompted their use in two frequently intertwined conditions, heart failure and chronic kidney disease. Their unique mechanism of action makes SGLT2i an attractive option also to lower the rate of cardiac events and improve overall survival of oncological patients with preexisting cardiovascular risk and/or candidate to receive cardiotoxic therapies. This review will cover biological foundations and clinical evidence for SGLT2i modulating myocardial function and metabolism, with a focus on their possible use as cardioprotective agents in the cardio-oncology settings. Furthermore, we will explore recently emerged SGLT2i effects on hematopoiesis and immune system, carrying the potential of attenuating tumor growth and chemotherapy-induced cytopenias.
