Background and Objectives: Diabetes mellitus (DM) is a complex disease affecting the whole metabolic balance of the body and resulting in multiple organ complications: cardiovascular, neuronal, renal, etc. Our study focuses on investigating the effect of zinc chloride (Zn) on certain blood parameters suggestive for assessing the metabolic disturbances, the liver and kidney function, the oxidative stress and the immune defense capacity in experimental-induced DM with streptozotocin (STZ) and cholesterol in rats. Materials and Methods: The animals were assigned to three groups, as follows: Group 1 (Control): buffer citrate solution 0.1 mL/100 g body; Group 2 (STZ): 20 mg/kg body STZ and fat diet (10 g cholesterol/100 g diet); Group 3 (STZ+Zn): 20 mg/kg body STZ + 5 mg/kg body Zn chloride and the same fat diet. DM was induced by administering STZ in a single take daily, for three consecutive days, Zn and citrate buffer were administered orally for a month. The protocol was approved by the Ethics Committee of the University ‘Grigore T Popa’ Iasi, in agreement with the International Regulations about the handling of laboratory animals. Results: The use of STZ in rats fed with cholesterol was correlated with important weight gain, hyperglycemia, the intensification of the transaminases activity and the increase in serum alkaline phosphatase, cholesterol, triglyceride, urea, creatinine and in malondialdehyde. Conclusions: The treatment with Zn resulted in weight loss and a decrease in blood sugar in diabetic rats. Supplementation with Zn notably reduced oxidative stress, preserved the pancreatic architecture and restored the liver and kidney function and structure in STZ-induced DM in rats.

Background: Diabetic kidney disease is a common and serious complication of type 2 diabetes mellitus (T2DM) and represents a major contributor to chronic kidney disease (CKD) globally. While sodium-glucose cotransporter-2 (SGLT2) inhibitors have demonstrated significant renoprotective effects, the potential advantages of combining these agents with micronutrients such as zinc (Zn), known for its antioxidant, anti-inflammatory, and metabolic regulatory properties, have not been fully investigated. This study aimed to assess the effects of dapagliflozin (DAPA) and empagliflozin (EMPA), administered either alone or alongside Zn, in an experimental diabetes model. Methods: T2DM was induced in Sprague-Dawley rats through a high-fat diet (HFD) followed by a low dose of streptozotocin (STZ). Seven experimental groups were established: a control group, an untreated diabetic group, and treatment groups receiving DAPA, EMPA, or their combinations with Zn. Metabolic parameters, renal function, and histopathological alterations were assessed, while immunohistochemistry was used to evaluate the expression of inflammatory and fibrotic markers. Results: Diabetic rats exhibited sustained hyperglycemia, metabolic imbalance, and significant renal damage, accompanied by elevated levels of inflammatory and fibrotic markers. Treatment with SGLT2 inhibitors improved metabolic status, mitigated kidney injury, and reduced inflammatory marker expression. Zn association further potentiated these effects, with the most pronounced benefits observed when combined with EMPA. Conclusions: These findings suggest that SGLT2 inhibitors exert strong renoprotective effects in experimental diabetic nephropathy. Zn supplementation may amplify these benefits through its antioxidant and anti-inflammatory actions. The combination of EMPA and Zn demonstrated the greatest protective effect, highlighting the potential of multi-target therapeutic strategies in diabetic kidney disease.

(1) Background. We aimed to assess long-term efficacy and safety in inadequately controlled type 2 diabetes (T2DM) of two SGLT-2 inhibitors: empagliflozin (Empa) and dapagliflozin (Dapa), combined with metformin, other oral antidiabetics or insulin, according to the protocols in Romania. (2) Methods. The data of 100 patients treated for T2DM with associated dyslipidemia and/or cardiovascular diseases at the University Hospital and Consultmed Medical Center in Iasi were retrospectively reviewed (2017–2021). In total, 48 patients had received dapagliflozin (10 mg with oral antidiabetics or insulin) and 52 patients received empagliflozin (10 mg /25 mg with oral antidiabetics). (3) Results. In both groups, the lowering of BMI was significant: Dapa group (32.04 ± 4.49 vs. 31.40 ± 4.18 kg/m²; p = 0.006), and Empa group (34.16 ± 5.08 vs. 33.17 ± 4.99 kg/m²; p = 0.002). Blood sugar average levels decreased significantly (170 vs. 136 mg/dL; p = 0.001 for Dapa; 163 vs. 140 mg/dL; p = 0.002 for Empa) and also average levels of HbA1c (7.90% vs. 7.51%; p = 0,01 for Dapa; 7.72% vs. 7.35%; p = 0.004 for Empa). (4) Conclusions. Better results in all variables were observed in younger male patients with a shorter duration of diabetes and threshold BMI levels of 34.1, treated with SGLT2, and more significantly with Empa.

Type 2 diabetes mellitus (T2DM) is associated with chronic hyperglycemia, inflammation, and progressive hepatic and pancreatic dysfunction. Although sodium-glucose cotransporter 2 (SGLT2) inhibitors exert metabolic and organ-protective effects, their ability to preserve pancreatic architecture and attenuate diabetes-associated hepatic injury, particularly combined with nutritional interventions, remains insufficiently explored. This study investigated the protective effects of dapagliflozin (DAPA) and empagliflozin (EMPA), alone or combined with zinc (Zn), on hepatic and pancreatic alterations in experimental diabetes. Methods: Diabetes was induced in male Sprague–Dawley rats using streptozotocin (STZ) and high fat diet (HFD). Diabetic animals received DAPA, EMPA, Zn, or SGLT2 inhibitor–Zn combinations for four weeks. Hepatic biochemical parameters, lipid profile, histopathology, pancreatic morphometry, and insulin immunoreactivity were evaluated. Diabetes induced hepatic and pancreatic alterations, including elevated liver injury markers, hepatocellular degeneration, reduced islet number and β-cell density, and diminished insulin immunoreactivity. DAPA and EMPA attenuated these changes, with greater improvements following Zn combination therapy. EMPA + Zn produced the most favorable response, improving hepatic architecture, reducing VCAM-1, ICAM-1, and NF-κB expression, preserving islet morphology, increasing β-cell density, and enhancing insulin immunoreactivity. SGLT2 inhibitors attenuated diabetes-associated hepatic and pancreatic alterations in this experimental model, while Zn supplementation was associated with additional tissue-preserving effects, particularly when combined with EMPA. These findings support further investigation of combined SGLT2 inhibition and Zn supplementation as an experimental approach to diabetes-associated organ injury; however, their clinical relevance remains to be established.