Search Results (101)

Although glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium–glucose co-transporter 2 inhibitors (SGLT2is) have demonstrated protective effects against chronic kidney disease, their impact on acute kidney injury (AKI) remains unclear. AKI and chronic kidney disease share overlapping clinical features but differ in pathogenesis and risk profiles. Previous analyses often grouped diverse agents into single categories, potentially concealing medication-specific renal risks. Given the widespread assumption of renoprotection, particularly among newer agents, there is a need to evaluate the comparative AKI risk of GLP-1RAs and SGLT2is at the individual drug and dose level. We performed a Bayesian network meta-analysis (NMA) following Cochrane-recommended methodology for safety-focused assessments. A systematic literature search across eight databases identified 67 randomized controlled trials (RCTs), including 199,877 participants. Eligible trials reported AKI outcomes or sufficiently explicit acute renal injury-related events associated with GLP-1RA or SGLT2i interventions. The primary outcome was the incidence of AKI; all-cause dropout was analyzed as a general tolerability measure. Odds ratios (ORs) with 95% credible intervals (CrIs) were calculated, and surface under the cumulative ranking curves (SUCRA) were used to estimate relative safety rankings. Only high-dose tirzepatide (10–15 mg/week) was associated with a significantly increased risk of AKI compared to controls (absolute risk difference: 0.28%; number needed to harm: 357). In contrast, lixisenatide, high-dose canagliflozin (300 mg/day), empagliflozin, and dapagliflozin were associated with reduced AKI risk. Risk rankings consistently identified high-dose tirzepatide as the most likely to induce AKI. Subgroup analyses excluding patients with baseline renal impairment yielded consistent results. High-dose tirzepatide may elevate AKI risk despite its metabolic benefits. Clinicians should assess renal vulnerability when prescribing GLP-1RAs or SGLT2is, particularly in patients with preserved kidney function. Further prospective trials are needed to clarify causal mechanisms and inform clinical decision-making. Full article

Sodium glucose-1 cotransporter (SGLT1) is a low-capacity, high-affinity glucose transporter expressed in the proximal renal tubule. It is also expressed in different human tissues and, primarily, in the brush border of the small intestine. At this level, SGLT1 inhibition results in an increase in glucose supply to the distal intestine with a reduction in intestinal pH and a consequent alteration of the intestinal microbiota. Specifically, SGLT1 inhibitors (SGLT1is) lead to an intensification of the production of short-chain fatty acids (SCFAs) and an enhancement of the incretin pathway. Potential mechanisms by which SGLT1is could reduce the occurrence of stroke and myocardial infarction may therefore involve the anti-inflammatory, anti-fibrotic and anti-atherosclerotic effects associated with an increased production of endogenous glucagon-like peptide-1 (GLP-1). Full article

Annona cherimola is a plant species widely used in Mexican traditional medicine, particularly in the management of diabetes. This study aimed to investigate the antihyperglycemic properties of the petroleum ether extract of A. cherimola leaves (PEEAcL), as well as to evaluate their effects on glycated hemoglobin and toxicity. In addition, the work was directed to determine its potential as an SGLT-1 and α-glucosidase inhibitor. The effect as a potential SGLT-1 and α-glucosidase inhibitor of PEEAcL was evaluated utilizing intestinal glucose absorption (IGA), oral glucose tolerance (OGT), oral sucrose tolerance (OST) and intestinal sucrose hydrolysis (ISH) tests. PEEAcL administered at doses of 200 mg/kg showed significant antihyperglycemic activity after 1 h of treatment, and the maximum effect was seen at 4 h in male and female diabetic mice. In the OST, OLT, and OGT tests, PEEAcL generated a reduction in the postprandial glucose peak at 2 h after the administration of a carbohydrate load, showing an effect comparable to that of acarbose and canagliflozin. In the IGA trial, PEEAcL significantly reduced glucose uptake in the small intestine. Similarly, in the ISH, PEEAcL recorded a significant reduction in glucose concentration in the external aqueous medium. Taken together, these results suggest that the antihyperglycemic effect of PEEAcL could be mediated, at least in part, by inhibition of SGLT-1 and the enzyme α-glucosidase. Full article

Background: Sodium–glucose cotransporter-2 inhibitors (SGLT2i) are widely used in older adults for diabetes, heart failure, and kidney disease. This is the first network meta-analysis focusing on the effects of SGLT2i in older adults. Methods: Databases were searched for randomized clinical trials comparing SGLT2i against non-SGLT2i controls or other SGLT2i in relevant populations. Key safety outcomes included acute renal failure (ARF), genital infections, volume depletion, mortality, and serious adverse events (SAEs). Pooled odds ratios (OR) with 95% confidence intervals (CI) were generated using random-effects models for direct and mixed treatment comparisons. Results: From 97 included trials in the meta-analysis, SGLT2i versus non-SGLT2i were associated with reduced risks of ARF (OR 0.86, 95% CI 0.79–0.94), mortality (OR 0.84, 0.75–0.93), and SAEs (OR 0.84, 0.78–0.89), but increased risks of genital infections (OR 3.32, 2.68–4.12) and volume depletion (OR 1.18, 1.09–1.27). The risk of genital infections was observed more frequently with higher doses (high-dose OR 4.73 vs. low-dose OR 2.90) and escalated sharply with age (≥75 years OR 9.29, 3.13–27.6). The mortality benefit was strongest in adults ≥75 years (OR 0.58, 0.38–0.88). Intra-class analysis revealed distinct safety profiles; for instance, empagliflozin reduced the ARF risk, while sotagliflozin increased the volume depletion risk. Bootstrap and trial sequential analyses confirmed the results’ robustness. Grading of Recommendations Assessment, Development, and Evaluation assessment indicated moderate certainty of evidence. Conclusions: In older adults, SGLT2i maintain a favorable benefit–risk profile, with significant reductions in mortality and SAEs, though risks of genital infections and volume depletion require vigilance. The risk of genital infections exhibits a strong dose–response relationship and increases markedly in the oldest adults, while the mortality benefit appears to be most pronounced in those aged 75 years and older. This study provides actionable insights for personalized therapy in geriatric care. Full article

Glucose transport dysregulation plays a central role in pathophysiology of diabetes mellitus. Synthetic agents like sotagliflozin or canagliflozin have been discovered recently and are currently used as antidiabetic therapy, providing great efficacy in modulation of glucose transport. However, the search for additional compounds with antidiabetic potential continues, as researchers aim to identify new molecules that may complement or enhance existing therapies. Numerous plant-derived compounds are currently under investigation and have demonstrated promising effects, while others remain far less studied yet could hold meaningful potential. In this context, resveratrol and its oligomers, including ε-viniferin, have gained attention due to promising in vitro findings, particularly due to influencing glucose homeostasis through direct SGLT interaction, indirect metabolic pathways, or a combination of both. This review examines their molecular mechanisms, absorption profiles, and inhibitory activity on sodium–glucose cotransporters SGLT1 and SGLT2. While resveratrol demonstrates high cellular uptake and metabolic conversion, ε-viniferin exhibits poor intestinal permeability, suggesting limited systemic bioavailability but potential local activity at the intestinal epithelium. Gliflozins are clinically validated dual SGLT1/SGLT2 inhibitors that offer superior glucose-lowering efficacy and organ protection. In regard to stilbenoids, they offer promising in vitro results, though in vivo studies and clinical trials are scarce. Understanding resveratrol and viniferin pharmacokinetics, target interactions, and limitations is vital for their development as potential complementary or even alternative antidiabetic therapies. Full article

Increasing evidence implicates mitochondrial/cellular dynamics in ischemia reperfusion (I/R)-induced acute kidney injury (AKI). Sodium-glucose-co-transporter-2 inhibitors (SGLT2is, e.g., canagliflozin, CG) have been shown to mitigate I/R-induced AKI. Here, we hypothesized that CG-improved AKI was associated with altered mitochondrial dynamics and apoptosis in a previously established swine model. CG (300 mg, PO) significantly increased pro-apoptotic genes Bid, Bad, Bax, Bak1 and Casp1 expression (all p < 0.05). Pink1 (p = 0.0019), Optn (p = 0.038), and Map1lc3 (p = 0.0093) expression also increased with CG, implicating mitophagy; PINK1 protein levels were unchanged. The expression of mitochondrial fission regulator Fis1 increased with CG treatment (p = 0.0015) while fusion regulator Opa1 expression decreased (p = 0.038). TUNEL staining showed increased apoptosis primarily in damaged proximal tubular cells of CG animals. Ki67 staining revealed I/R-injury increased cell proliferation throughout the kidney, which was significantly attenuated with CG. Moreover, correlative analysis revealed that AKI severity positively correlated with cell proliferation. In this large animal model, CG reduced AKI via increased mitochondrial fission and pro-apoptotic gene expression, potentiating clearance of damaged mitochondria, and decreased cell proliferation. Future studies should evaluate other SGLT2is as a potential therapeutic for I/R AKI. Full article

Background/Objectives: Canagliflozin (CFZ) is the first sodium glucose co-transporter 2 (SGLT-2) inhibitor and is characterized by poor water solubility and permeability, resulting in low oral bioavailability. In this study, a CFZ nanosuspension (CFZ-NS) was converted into a solid form to improve the physical stability of CFZ nanocrystals (CFZ-NCs) and to enable formulation as a tablet dosage form. Methods: To achieve adequate redispersibility of dried CFZ-NCs, fluid bed granulation and spray-drying methods were employed, and the effects of critical process parameters were investigated. The stability of spray-dried nanocrystal tablets (NCs-SD-TAB) was evaluated over a three-month period under storage conditions of 25 ± 2 °C with 60 ± 5% relative humidity (RH) and 40 ± 2 °C with 75 ± 5% RH. Results: The highest redispersibility index (94%) was obtained using the spray-drying method. Tablets prepared with spray-dried NCs-SD-TAB exhibited a significantly higher in vitro dissolution rate under non-sink conditions compared with control tablets prepared using unprocessed CFZ with the same excipients, as well as the marketed product. NCs-SD-TAB showed an approximately three-fold increase in drug release at 15 min in 0.1 N HCl, with a pH 4.5 acetate buffer and pH 6.8 phosphate buffer, which simulate gastrointestinal pH conditions, relative to the marketed product. Conclusions: Overall, these results indicate that nanocrystal technology represents a promising approach for CFZ as an improved oral drug-delivery system, primarily due to its solubility enhancement capabilities. Full article

Canagliflozin (CFZ), a sodium–glucose cotransporter 2 (SGLT2) inhibitor, is extensively utilized in the management of type 2 diabetes. Among its various polymorphic forms, the hemi-hydrate (Hemi-CFZ) has been selected as the active pharmaceutical ingredient (API) for CFZ tablets due to its superior solubility. However, during the production, storage, and transportation of CFZ tablets, Hemi-CFZ can undergo transformations into anhydrous (An-CFZ) and monohydrate (Mono-CFZ) forms under the influence of environmental factors such as temperature, humidity, and pressure, which may adversely impact the bioavailability and clinical efficacy of CFZ tablets. Therefore, it is imperative to develop rapid, accurate, non-destructive, and non-contact methods for quantifying An-CFZ and Mono-CFZ content in CFZ tablets to control polymorphic impurity levels and ensure product quality. This research evaluated the feasibility and reliability of using near-infrared spectroscopy (NIR) combined with partial least squares regression (PLSR) for simultaneous quantitative analysis of An-CFZ and Mono-CFZ in CFZ tablets, elucidating the quantifying mechanisms of the quantitative analysis model. Orthogonal experiments were designed to investigate the effects of different pretreatment methods and ant colony optimization (ACO) algorithms on the performance of quantitative models. An optimal PLSR model for simultaneous quantification of An-CFZ and Mono-CFZ in CFZ tablets was established and validated over a concentration range of 0.0000 to 10.0000 w/w%. The resulting model, Y_{An-CFZ/Mono-CFZ} = 0.0207 + 0.9919 X, achieved an R² value of 0.9919. By analyzing the relationship between the NIR spectral signals selected by the ACO algorithm and the molecular structure information of An-CFZ and Mono-CFZ, we demonstrated the feasibility and reliability of the NIR-PLSR approach for quantifying these polymorphic forms. Additionally, the mechanism of PLSR quantitative analysis was further explained through the variance contribution rates of latent variables (LVs), the correlations between LVs loadings and tablets composition, and the relationships between LV scores and An-CFZ/Mono-CFZ content. This study not only provides a robust method and theoretical foundation for monitoring An-CFZ and Mono-CFZ content in CFZ tablets throughout production, processing, storage, and transportation, but also offers a reliable methodological reference for the simultaneous quantitative analysis and quality control of multiple polymorphic impurities in other similar drugs. Full article

Glucagon-like peptide-1 (GLP-1) receptor agonists and sodium–glucose cotransporter-2 (SGLT2) inhibitors have reshaped pharmacological management of type 2 diabetes, but emerging safety signals suggest a possible association with intestinal obstruction. Because many candidates for these agents already harbor risk factors for ileus and bowel obstruction, clarifying agent- and dose-specific gastrointestinal safety is clinically important. We aimed to re-evaluate the risk of intestinal obstruction across individual GLP-1 receptor agonists and SGLT2 inhibitors, with particular attention to dose stratification. We systematically searched eight databases through 21 January 2025 to identify randomized controlled trials (RCTs) comparing GLP-1 receptor agonists or SGLT2 inhibitors with placebo or active comparators in adults. The primary outcome was incident intestinal obstruction (small or large bowel). A frequentist random-effects network meta-analysis estimated odds ratios (ORs) with 95% confidence intervals (CIs) across drugs and dose tiers; Bayesian models and surface under the cumulative ranking (SUCRA) metrics were used for sensitivity analyses and treatment ranking. Risk of bias and certainty of evidence were assessed with standard Cochrane and GRADE-adapted tools. Fifty RCTs (47 publications; 192,359 participants) met inclusion criteria. Overall, canagliflozin use was associated with a higher incidence of intestinal obstruction than control therapies (OR 2.56, 95% CI 1.01–6.49), corresponding to an absolute risk difference of 0.15% and a number needed to harm of 658. High-dose canagliflozin (300 mg/day) showed the clearest signal (OR 3.42, 95% CI 1.08–10.76). In contrast, liraglutide was associated with a lower risk of intestinal obstruction (OR 0.44, 95% CI 0.24–0.81), with an absolute risk reduction of 0.34% and a number needed to treat of 295. No other GLP-1 receptor agonist or SGLT2 inhibitor demonstrated a statistically significant increase in obstruction risk. Frequentist and Bayesian analyses yielded concordant estimates and rankings. From a randomized-trial perspective, intestinal obstruction risk is not elevated for most GLP-1 receptor agonists and SGLT2 inhibitors. A dose-dependent safety signal was observed only for high-dose canagliflozin, whereas liraglutide may confer a protective effect. These findings refine gastrointestinal safety profiles for modern antidiabetic agents and may inform perioperative bowel management, drug selection, and dose optimization in patients at risk for ileus or adhesive obstruction. Full article

Background: SGLT2 inhibitors are key therapies in heart failure (HF), but their combined multidomain effects have not been analyzed together. Methods: We conducted a PROSPERO-registered (CRD420251235850) systematic review and meta-analysis of all randomized controlled trials (RCTs) comparing SGLT2i (dapagliflozin, empagliflozin, canagliflozin, sotagliflozin) with placebo in adults with HF, regardless of ejection fraction or diabetes status. We searched PubMed/MEDLINE, Embase, Cochrane CENTRAL, and Web of Science through 1 February 2025. Outcomes were grouped into four domains: (1) clinical events, (2) symptoms/health status (Kansas City Cardiomyopathy Questionnaire, KCCQ), (3) functional capacity (6 min walk distance, peak VO₂), and (4) cardiac remodeling/energetics (cardiac MRI, 31P-MRS). We used random-effects models with Hartung–Knapp adjustment and assessed heterogeneity by I² and prediction intervals. Results: Eleven RCTs with 23,812 patients (HFrEF, HFmrEF, HFpEF, and acute or recently decompensated HF) were included. SGLT2i lowered the risk of cardiovascular death or first HF hospitalization by 23% (HR 0.77, 95% CI 0.72–0.82; p < 0.0001; I² = 28%; prediction interval 0.68–0.87), with similar effects across ejection fraction, diabetes status, and presentation type. All-cause and cardiovascular mortality dropped by 12% (HR 0.88, 95% CI 0.81–0.96) and 14% (HR 0.86, 95% CI 0.78–0.95), respectively. SGLT2i improved KCCQ—Clinical Summary Score by 4.6 points (95% CI 3.4–5.8; p < 0.0001) and increased the odds of a ≥5-point improvement (OR 1.49, 95% CI 1.32–1.68; NNT = 12). Six-minute walk distance increased by 21.8 m (95% CI 9.4–34.2; p = 0.001), and mechanistic trials showed significant reverse remodeling (ΔLVEDV −19.8 mL, ΔLVEF +6.1%; both p < 0.001). No improvement was observed in myocardial PCr/ATP ratio. Safety was favorable, with no excess ketoacidosis or severe hypoglycemia. Conclusions: This multidomain synthesis demonstrates that SGLT2 inhibitors provide consistent, robust reductions in mortality and hospitalizations, while also delivering early, clinically meaningful improvements across multiple patient-centered domains. These results establish SGLT2i as a foundational component of contemporary HF management. Full article

The kidneys have a high-energy demand, relying on great rates of mitochondrial oxidative phosphorylation. Excessive glucose in the tubules leads to defective fatty acid oxidation, playing a key role in tubular injury and diabetic kidney disease progression. Besides its glucose-lowering action, canagliflozin (CANA) promotes kidney protective effects. We aimed to investigate whether the demonstrated kidney protective effects are extended to mitochondrial function and remodeling in proximal tubular cells from hypertensive–diabetic mice. Four weeks after streptozocin (STZ) induction of type 1 diabetes in genetic hypertensive (Lin) mice, they were fed either CANA-infused chow or a regular diet for 1 week. CANA treatment reverted the albuminuric state in LinSTZ mice. In PTECs from male mice, CANA promoted a complex mitochondrial network with less spherical and more branched organelles, with evidence of increased fusion. Those improvements reflected on the mitochondria bioenergetics, where CANA treatment induced an augmented baseline and maximum respiration rate, ATP production, and mitochondria membrane potential in PTECs, compared to LinSTZ. In females, CANA produced a milder response, increasing the mitochondrial network without affecting bioenergetics. In conclusion, in vivo CANA treatment positively affects proximal tubular cells’ mitochondria in male hypertensive–diabetic mice with a minor impact in females. The improvement in mitochondrial function and structure might be key to the kidney-protective effects of CANA. Full article

Recent clinical trials have shown significant cardioprotective effects of antidiabetic sodium-glucose cotransporter 2 inhibitors (SGLT2i), including canagliflozin, empagliflozin, and dapagliflozin. These drugs significantly reduce hospitalizations for heart failure with reduced and preserved ejection fraction in both diabetic and non-diabetic patients. Yet, the mechanisms underlying their protective effects, beyond their glucose-lowering properties, remain poorly understood. This study aimed to elucidate the direct effects of SGLT2i on cardiac fibroblasts, key mediators of myocardial fibrosis, ventricular remodeling, and heart failure. Using primary human cardiac fibroblast cultures, we compared the impact of canagliflozin, empagliflozin, and dapagliflozin on fibroblast properties. All three inhibitors significantly prevented myofibroblast differentiation. Notably, only canagliflozin significantly reduced fibroblast proliferation and migration. While all SGLT2i increased AMP-activated protein kinase (AMPK) phosphorylation, their effects on myodifferentiation were AMPK-independent. In contrast, the effect of canagliflozin on migration was partially dependent on AMPK, as demonstrated using the AMPK inhibitor BAY-3827. These findings reveal distinct cellular effects of individual SGLT2i on cardiac fibroblasts, suggesting heterogeneous potential to modulate extracellular matrix remodeling. Among them, canagliflozin may be more potent in preventing myocardial fibrosis in the context of heart failure. Full article

Objectives: The objective of this study was to enhance the solubility and bioavailability of canagliflozin (CFZ) using a spray drying technique with a Quality-by-Design (QbD) approach. Methods: The formulation of CFZ-loaded solid dispersions (CFZ-SDs) was optimized using a Box–Behnken design (BBD) with three factors at three levels, resulting in a total of fifteen experiments, including three central point replicates. The design space was determined using the BBD, and the optimized CFZ-SD was evaluated for reproducibility, morphology, and physical properties and subjected to in vitro and in vivo tests. Results: The optimal values for each X factor were identified using a response optimization tool, achieving a yield (Y1) of 62.8%, a solubility (Y2) of 9941 μg/mL, and a particle size (Y3) of 5.89 μm, all of which were within the 95% prediction interval (PI). Additionally, amorphization induced by spray drying was confirmed for the optimized CFZ-SD using scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and powder X-ray diffraction (PXRD) analyses. In in vitro dissolution tests, the final dissolution rate of the CFZ-SD increased 3.58-fold at pH 1.2 and 3.84-fold at pH 6.8 compared to an Invokana^® tablet. In addition, relative to CFZ, it showed an 8.67-fold and 8.85-fold increase at pH 1.2 and pH 6.8, respectively. The in vivo pharmacokinetic behavior of CFZ and the CFZ-SD was evaluated in Sprague–Dawley rats following oral administration at a dose of 5 mg/kg. The AUC of the CFZ-SD increased 1.9-fold compared to that of CFZ. Conclusions: In this study, a solid dispersion (SD) formulation of CFZ, a BCS class IV SGLT2 inhibitor, was developed and optimized using a QbD approach to enhance solubility and oral bioavailability. Full article

Background: The United Arab Emirates (UAE) faces a high burden of type 2 diabetes mellitus (T2DM) and its complications. While sodium-glucose cotransporter-2 inhibitors (SGLT2i) have demonstrated cardiorenal benefits in clinical trials, real-world evidence on their association with calculated cardiovascular risk in Middle Eastern populations remains limited. This study evaluated the long-term real-world outcomes associated with SGLT2i use in Emirati patients with T2DM. Methods: We conducted a retrospective observational study of patients with T2DM initiated on SGLT2i (empagliflozin, dapagliflozin, or canagliflozin) at Tawam Hospital, UAE, between 1 January 2018 and 31 December 2018. Patients were followed for up to 5 years. Primary outcomes included changes in glycated hemoglobin (HbA1c), estimated glomerular filtration rate (eGFR), and body mass index (BMI). A key secondary outcome was the change in 10-year atherosclerotic cardiovascular disease (ASCVD) risk, calculated using the ACC/AHA Pooled Cohort Equations. Results: We included 185 patients (mean age 57 ± 12 years, 56.2% female), with 107 (57.8%) receiving empagliflozin, 54 (29.2%) dapagliflozin, 11 (5.9%) canagliflozin, and 13 (7.0%) who switched between agents. Significant improvements were observed in HbA1c (8.7 ± 1.8% to 8.2 ± 1.9%, p < 0.001), while eGFR showed preservation of renal function with an annual decline of 1.1 mL/min/1.73 m². Among 120 patients eligible for ASCVD risk assessment (excluding 65 with established cardiovascular disease), the mean 10-year ASCVD risk decreased from 22.3 ± 5.3% at baseline to 19.3 ± 4.9% at 5 years (absolute reduction −3.0%, 95% CI −2.4 to −3.6%, p < 0.001). Serious adverse events were rare, including acute kidney injury (1.1%) and fractures (1.6%). No episodes of diabetic ketoacidosis or severe hypoglycemia were observed. Conclusions: In this real-world cohort from the UAE, SGLT2 inhibitor use was associated with sustained glycemic control, preserved renal function, and lower calculated 10-year cardiovascular risk over 5 years. These observational findings, noted in the context of comprehensive risk factor management, support the potential benefits of SGLT2i in high-risk Middle Eastern patients with T2DM, though prospective controlled studies are needed to confirm causality. Full article

Patients with active cancer and cancer survivors are at a markedly increased risk for developing cardiovascular comorbidities, including heart failure, coronary artery disease, and renal dysfunction, which are often compounded by the cardiotoxic effects of cancer therapies. This heightened cardiovascular vulnerability underscores the urgent need for effective, safe, and evidence-based cardioprotective strategies to reduce both cardiovascular morbidity and mortality. Sodium-glucose cotransporter 2 inhibitors (SGLT2is), a class of drugs originally developed for the treatment of type 2 diabetes, have demonstrated significant cardiovascular and renal benefits in high-risk populations, independent of glycemic control. Among the currently available SGLT2i, such as empagliflozin, canagliflozin, dapagliflozin, and sotagliflozin, there is growing evidence supporting their role in reducing major adverse cardiovascular events (MACEs), hospitalization for heart failure, and the progression of chronic kidney disease. Recent preclinical and clinical data suggest that SGLT2is exert cardioprotective effects through multiple mechanisms, including the modulation of inflammasome activity, specifically by reducing NLRP3 inflammasome activation and MyD88-dependent signaling, which are critical drivers of cardiac inflammation and fibrosis. Moreover, SGLT2is have been shown to enhance mitochondrial viability in cardiac cells, promoting improved cellular energy metabolism and function, thus mitigating cardiotoxicity. This narrative review critically evaluates the emerging evidence on the cardiorenal protective mechanisms of SGLT2is, with a particular focus on their potential role in cardio-oncology. We explore the common pathophysiological pathways between cardiovascular dysfunction and cancer, the molecular rationale for the use of SGLT2is in cancer patients, and the potential benefits in both primary and secondary prevention of cardiovascular toxicity related to oncological treatments. The aim is to propose a therapeutic paradigm utilizing SGLT2is to reduce cardiovascular mortality, MACE, and the burden of cardiotoxicity in high-risk oncology patients, fostering an integrated approach to cardio-oncology care. Full article