Type 2 diabetes mellitus (T2DM) is a progressive metabolic disease that necessitates individualized therapeutic strategies focusing on both glycemic control and the mitigation of comorbidities. In recent years, sodium-glucose cotransporter-2 (SGLT2) inhibitors have emerged as a cornerstone of modern treatment due to their unique renal mechanism of action. This review summarizes the metabolic mechanisms, pleiotropic effects, and clinical significance of SGLT2 inhibitors in the management of T2DM. This review provides an updated overview of the metabolic and systemic effects of SGLT2 inhibition. By promoting glycosuria, SGLT2 inhibitors induce a negative energy balance that contributes to modest weight loss, improved body composition, and beneficial alterations in lipid metabolism. Beyond their metabolic effects, accumulating preclinical evidence suggests that SGLT2 inhibitors exert anti-inflammatory and antifibrotic actions, partly through modulation of macrophage polarization and attenuation of oxidative stress. The clinical utility of SGLT2 inhibitors is highlighted through the review of major cardiovascular and renal outcome trials, which confirm significant benefits in reducing heart failure hospitalizations and slowing the progression of chronic kidney disease. Finally, we integrate these findings into the context of the latest international guidelines while addressing safety profiles, the rationale for combination therapies, and the transition toward a personalized, risk-based management approach in T2DM.

Background: Although endothelial mesenchymal transition (EndMT) has been characterized as a basic process in embryogenesis, EndMT is the mechanism that accelerates the development of cardiovascular diseases, including heart failure, aging, and complications of diabetes or hypertension as well. Endothelial cells lose their distinct markers and take on a mesenchymal phenotype during EndMT, expressing distinct products. Methods: In this study, type 1 Diabetes mellitus (T1DM) was induced in rats with streptozotocin (STZ) by intraperitoneal injection at a 60 mg/kg dose. Diabetic rats were randomly divided into two groups, namely, control and diabetic rats, for 4 weeks. Heart, aorta, and plasma samples were collected at the end of 4 weeks. Sequentially, biochemical parameters, cytokines, reactive oxygen species (ROS), protein expression of EndMT markers (Chemokine C-X-C motif ligand-1 (CXCL-1), vimentin, citrullinated histone H3 (H3Cit), α-smooth muscle actin (α-SMA), and transforming growth factor beta (TGF-β) and versican), components of the extracellular matrix (matrix metalloproteinase 2 (MMP-2), tissue inhibitor of metalloproteinase-1(TIMP-1), and discoidin domain tyrosine kinase receptor 2 (DDR-2)) were detected by ELISA or Western blot, respectively. Results: Cytokines and ROS were increased in diabetic hearts, which induced partial EndMT. Among EndMT markers, histone citrullination, α-SMA, and CXCL-1 were increased; vimentin was decreased in DM. The endothelial marker endothelin-1 was significantly higher in the aortas of DM rats. Interestingly, TGF-β showed a significant decrease in the diabetic heart, plasma, and aorta. Additionally, MMP-2/TIMP-1 levels also decreased in DM. Conclusions: To sum up, the identification of molecules and regulatory pathways involved in EndMT provided novel therapeutic approaches for cardiac pathophysiological conditions.

The present study was conducted in type 1 diabetic (T1DM) patients to evaluate the metabolic and glycemic control as well as the manifestations of neuropathy. The impact of continuous glucose monitoring (CGM) on the measured parameters was also analyzed. A total of 61 T1DM patients (age: 42.5 ± 1.8 years, DM duration: 22.8 ± 1.6 years, mean ± SE) participated in the study. In total, 24 patients had CGM sensors and 37 did not. Cardiovascular autonomic neuropathy was assessed using cardiovascular reflex tests. Peripheral sensory function was evaluated by a Neurometer and calibrated tuning fork on the upper and lower limbs. Metabolic status was characterized by the determination of triglycerides, high-density lipoprotein (HDL), low-density lipoprotein (LDL), total cholesterol, and glycated haemoglobin (HbA_1c). A positive correlation was found between HbA_1c and triglyceride levels (r = 0.28, p < 0.05). CGM users and non-users differed in triglyceride (0.9 ± 0.1 vs. 1.24 ± 0.12 mmol/L, p < 0.05), HDL cholesterol (1.7 ± 0.1 vs. 1.4 ± 0.1 p < 0.05 mmol/L), and HbA_1c (7.5 ± 0.2 vs. 8.3 ± 0.3%, p < 0.05) levels as well. Significant differences were found for the Valsalva ratio, Neurometer, and calibrated tuning fork results between CGM users and non-users. This study found a significant correlation between HbA_1c and triglyceride levels in T1DM. CGM use resulted in improved metabolic parameters and less autonomic and sensory nerve damage. As a novel finding, CGM is presumed to prevent both micro-, and macrovascular complications and, by this way, potentially reducing mortality rates.

Exercise training has demonstrated potential benefits in addressing the adverse effects of cardiovascular diseases, particularly myocardial infarction (MI). This study analyzed the cardioprotective effects of moderate exercise before and after MI in rats subjected to isoproterenol (ISO)-induced heart damage. Wistar rats were assigned to five groups: controls (CTRL), isoproterenol-treated (ISO), swimming before ISO (PRE + ISO), swimming after ISO (ISO + POST), and swimming both before and after ISO (PRE + ISO + POST). Cardiac function was assessed through echocardiography, while oxidative stress markers, Heme Oxygenase-1 (HO-1) and Myeloperoxidase (MPO), were quantified using biochemical assays and enzyme-linked immunosorbent assay (ELISA). Statistical analyses were conducted by one-way analysis of variance (ANOVA), accompanied by Tukey’s post hoc test. Exercise performed post-MI and both pre- and post-MI significantly reduced ISO-induced infarct size and improved left ventricular function (stroke volume (SV), ejection fraction (EF), and Tei index). HO-1 protein concentration and HO enzyme activity were restored, while swim training reduced the activity of MPO compared to the ISO group. Moderate exercise training, when appropriately timed, provides cardioprotection against ISO-induced myocardial damage by reducing oxidative stress and cardiac dysfunction.