Effects Of Dapagliflozin Research Articles

Impact of Dapagliflozin on Hepatic Lipid Metabolism and a Dynamic Model of Ketone Body Levels.

The rising prevalence of metabolic-associated steatotic liver disease emphasizes the need to understand its lipid metabolism. Dapagliflozin may improve hepatic steatosis but could also increase the risk of ketoacidosis by elevating β-hydroxybutyrate (KB) levels. This study investigates dapagliflozin's effects on hepatic lipid metabolism and quantifies KB levels in vivo. Male Sprague-Dawley rats were fed either a normal diet or a high-fat diet (HFD) for 12 weeks. The HFD rats were then divided into four subgroups to receive vehicle, 0.5 mg/kg, 1 mg/kg, and 3 mg/kg of dapagliflozin for four weeks. Free fatty acids (FFA) and KB levels were monitored, while protein and gene expression were analyzed. And a dynamic model of KB was developed for humans based on preclinical data. Dapagliflozin decreased body weight and visceral fat in HFD rats, increasing KB by upregulating CPT1a, HMGCS2, and HMGCL, and downregulating ACC. These changes correlated with reduced liver/fat index, liver pathology score, and oil-red staining area. A pharmacokinetic/pharmacodynamic (PK/PD) model was created from preclinical data to quantify KB levels in rats and validated in humans. Dapagliflozin reduces hepatic steatosis by enhancing fatty acid β-oxidation and ketogenesis and inhibiting fat synthesis. A dynamic model accurately predicts ketone body levels in treated individuals.

Comprehensive treatment with dapagliflozin in elderly chronic kidney disease patients: Clinical efficacy and impact on body composition.

Dapagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, is widely used for treating heart failure and chronic kidney disease (CKD). While its renoprotective effects are well established, concerns remain regarding its impact on muscle mass and function, especially in elderly patients. To assess the effects of dapagliflozin on renal function, body composition, and muscle strength in elderly CKD patients. Twelve elderly CKD patients (75.6±1.4years) were treated with dapagliflozin for 12months. Body composition, serum parameters, and muscle function were evaluated at baseline, 6months, and 12months. Measurements included changes in eGFR, liver function, HbA1c, and muscle strength. Dapagliflozin treatment stabilized eGFR without significant improvement, but proteinuria was notably reduced in most patients, indicating a positive renal effect. AST and ALT levels showed significant reduction after 12months, suggesting improved liver function. No significant changes were observed in body weight, BMI, or muscle mass. Muscle function, as measured by the 5-sit-to-stand test, improved significantly, while grip strength remained stable. No serious adverse events were reported. Dapagliflozin is a safe and effective treatment for CKD in elderly patients, demonstrating renal protection and improved liver function without adversely affecting muscle mass or strength. The study supports the use of dapagliflozin as part of a comprehensive approach, combining pharmacotherapy, lifestyle modification, and exercise to optimize patient outcomes in CKD management.

The Effect of Dapagliflozin on Heart Function in Animal Models of Cardiac Ischemia, A Systematic Review and Meta-analysis.

In this study, a meta-analysis was conducted to investigate the therapeutic effect of Dapagliflozin (DAPA) on animals suffering from myocardial ischemia reperfusion compared to the group that did not receive treatment. According to the inclusion and exclusion criteria two researchers performed the primary and secondary screening based on the title abstract and full text. After data extraction, meta-analysis was performed using STATA software. Standardized mean differences were used to analyze the results of the reported studies. Subgroup analysis and quality control of articles were also conducted. A total of 21 separate experiments showed that DAPA increased mean fractional shortening (%FS) and ejection fraction (%EF) compared to the untreated animals. A significant reduction in the weight and size of the infarcted area and significant increases in dp/dt+, dp/dt-, left ventricular end-systolic internal dimensions (LVIDs), left ventricular end-diastolic internal dimensions (LVIDd), Volume systole and Volume diastole were observed in treated animals. DAPA has the potential to become a candidate for the treatment of post-ischemic heart damage, pending animal and human studies to validate this.

EuroQol 5-Dimension Questionnaire in HeartFailure With Reduced, Mildly Reduced, and Preserved Ejection Fraction: A Patient-Level Analysis of DAPA-HF and DELIVER.

The value of generic quality of life (QoL) instruments in heart failure (HF) is uncertain. In this study, the authors sought to quantify individual dimension scores and the EuroQol 5-Dimension questionnaire (EQ-5D) Level Sum Score (LSS) in patients with HF with reduced, mildly reduced, or preserved ejection fraction, the association between those scores and outcomes, and the impact of treatment with dapagliflozin on the scores. Analyses were conducted using patient-level data from DAPA-HF and DELIVER trials. Cox proportional hazards regression models were used to assess the association between EQ-5D scores (each dimension and LSS) and clinical outcomes. Sankey diagrams were used to illustrate changes in individual patient EQ-5D dimensions from baseline to 8months' follow-up. Of the 11,007 patients randomized in DAPA-HF and DELIVER, 10,135 (92.1%) completed the instrument at baseline. Scores varied markedly by question with 37%, 30%, and 33% of patients reporting no, slight, or moderate or greater problem, respectively for mobility; 67%, 20%, and 13% for self-care; 40%, 33%, and 27% for usual activities; 45%, 32%, and 23% for pain/discomfort; and 57%, 27%, and 16% for anxiety/depression. Patients with higher (worse) EQ-5D-LSS were more frequently female, had more comorbidities, and had worse HF status. Compared with patients free from any problem across all dimensions (ie, an EQ-5D-LSS of 5), the HRs for the composite outcome of time to first cardiovascular death or worsening HF were 1.27 (95%CI: 1.10-1.47), 1.70 (95%CI: 1.46-1.98), and 2.31 (95%CI: 1.88-2.85) in patients with EQ-5D-LSS of 6-10, 11-15, and 16-25 points, respectively. Dapagliflozin led to greater improvement and less worsening in mobility (OR: 1.13 [95%CI: 1.04-1.23]; P = 0.004), self-care (OR: 1.13 [95%CI: 1.02-1.24]; P = 0.016), usual activities (OR:1.11 [95%CI: 1.02-1.21]; P = 0.015), and anxiety/depression (OR: 1.10 [95%CI: 1.01-1.21]; P = 0.034) after 8months. The number needed to treat for 1 patient to report improvement in EQ-5D-LSS was 31 (95%CI: 20-72). The EQ-5D revealed problems not often associated (eg, pain) with HF or commonly quantified in HF (eg, anxiety/depression). Dapagliflozin improved multiple QoL dimensions, and possibly anxiety/depression. (Study to Evaluate the Effect of Dapagliflozin on the Incidence of Worsening HeartFailure or Cardiovascular Death in Patients WithChronic HeartFailure [DAPA-HF]; NCT03036124; Dapagliflozin Evaluation to Improve the Lives of Patients WithPreserved Ejection Fraction HeartFailure [DELIVER]; NCT03619213).

Dapagliflozin alleviated seizures and cognition impairment in pilocarpine induced status epilepticus via suppressing microglia-mediated neuroinflammation and oxidative stress.

Status epilepticus (SE) is a neurological emergency with prolonged seizures leading to chronic epilepsy, cognitive impairment, and neuronal damage. Microglial activation, subsequent neuroinflammation and oxidative stress contribute to SE-induced neuronal injury. Single-cell sequencing has delineated the pro-inflammatory microenvironment in epileptic lesions, characterized by widespread microglial activation. Dapagliflozin, an inhibitor of sodium-glucose cotransporter 2 (SGLT2), has shown potential in modulating neuroinflammatory responses. This study aimed to investigate the effects of Dapagliflozin on seizure and cognitive impairment by alleviating microglia-mediated neuroinflammation, oxidative stress. Single-Cell Transcriptomic Analysis were used to reveal SLC5A2 cellular heterogeneity and subtype-specific signatures of Temporal lobe Epilepsy. Male C57BL/6 mice were administered pilocarpine. Dapagliflozin were injected immediately after the termination of SE and at 24-hour intervals after SE until sacrifice. The latency and seizure score were recorded. Morris water maze were used to evaluate cognitive function of mouse. The neuroinflammation cell model was induced by lipopolysaccharide(LPS) in BV2 cell. Immunofluorescent staining, immunohistochemistry, flow cytometry, western blot, RT-qPCR, ELISA etc were used to examine the activation of microglia, evaluate neuroinflammation and oxidative stress. The expression of SLC5A2 is up-regulated in microglia of epileptic patients. Administration of Dapagliflozin significantly reduced seizure activity and improved cognitive performance in SE mouse. Dapagliflozin reduced microglial activation, as indicated by downregulation of CD86, iNOS expression and increased CD206, Arg-1 level. Dapagliflozin decreased oxidative stress, as evidenced by reduced levels of malondialdehyde (MDA), reactive oxygen species (ROS), increased superoxide dismutase (SOD) and Glutathione (GSH) activity. In addition, Dapagliflozin treatment can rescured the neuronal damage and suppressed the release of inflammatory cytokines such as IL-6, IL-18 and IL-1β. Our findings suggest that Dapagliflozin exerts neuroprotective effects by modulating microglia-mediated neuroinflammation and oxidative stress. The inhibition of SGLT2 may represent a novel therapeutic strategy for the treatment of SE and associated cognitive impairments.

Protective effect of dapagliflozin on lipopolysaccharide-induced acute lung injury via the SIRT-1/PGC-1α pathway.

Acute systemic inflammation affects many organs and it occurs in a wide range of conditions such as acute lung injury (ALI). Inflammation-triggered oxidative pathways together with the caspase activation seen in ALI, result in apoptosis. Dapagliflozin (DPG) is an agent that is known to have oxidative stress-reducing and anti-inflammatory effects in many tissues. Thirty-two Wistar albino rats were divided into four groups: control, lipopolysaccharide (LPS) (5mg/kg), LPS + DPG (10mg/kg) and DPG. DPG was orally administered for five consecutive days LPS was intraperitoneally applied in a single dose on the fifth day and the animals were euthanized six hours after the last drug administration. Lung tissues were harvested. In addition to hematoxylin-eosin staining, caspase-3 (Cas-3) and tumor necrosis factor alpha (TNF-α) immunostainings were conducted. While total oxidant status (TOS), total antioxidant status (TAS), and oxidative stress index (OSI) were examined biochemically, Sirtuin-1 (SIRT-1), Peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (PGC-1α), B-cell lymphoma 2 (Bcl-2), and Bcl-2 associated X protein (Bax) were examined by PCR. Histopathological analysis revealed hyperemia, edema, inflammatory cell infiltration, and epithelial cell loss. In LPS group, Cas-3, TNF-α, TOS, OSI, and Bax values increased whereas SIRT-1, PGC-1α, and Bcl-2 values decreased. All these changes were restored with DPG treatment. DPG exhibited protective effects against inflammation, oxidative stress, and subsequent apoptosis observed in systemic inflammation-induced ALI likely through SIRT-1/ PGC-1α pathway.

Dapagliflozin plus calorie restriction for remission of type 2 diabetes: multicentre, double blind, randomised, placebo controlled trial

ObjectiveTo assess the effect of dapagliflozin plus calorie restriction on remission of type 2 diabetes.DesignMulticentre, double blind, randomised, placebo controlled trial.Setting16 centres in mainland China from 12 June 2020 to...

Impact of dapagliflozin on metabolic phenotype, hormone levels, and fertility in female mice after prolonged high-fat diet.

A long-term high-fat diet (HFD) cause obesity and infertility through hypothalamic inflammation and insulin resistance, leading to metabolic abnormalities and ovulation dysfunction. The sodium-glucose cotransporter 2 inhibitors (SGLT2i) have emerged as a treatment for type 2 diabetic patients, regulating adipose tissue metabolism, hypothalamic inflammation, and ovulation in women with polycystic ovary syndrome (PCOS). The study aimed to investigate the pharmacological effects of dapagliflozin on improving insulin resistance, energy metabolism, sex hormones, and fertility in female mice following prolonged consumption of HFD. At 6 weeks of age, female mice were fed a HFD and treated with dapagliflozin. Serum hormone concentrations and inflammatory factors in mice aged 28 weeks or 38 weeks were quantified using ultrasensitive enzyme-linked immunosorbent assays (ELISAs). Metabolic parameters were also assessed and documented at different stages of the experiment. At 34 weeks of age, half of the experimental mice in each of the four groups fed with standard chow were mated with male mice. Pregnancy rate, abortion rate, pregnancy-related deaths, and perinatal outcomes were systematically recorded. After 16 weeks of HFD feeding, dapagliflozin significantly attenuated visceral fat deposition, weight gain, glucose intolerance, and insulin resistance induced by the diet. However, these effects diminished after 32 weeks. Unexpectedly, neither HFD nor dapagliflozin treatment elicited any significant changes in serum IL-6 and TNFα levels. Throughout the experiment period, dapagliflozin exhibited favorable effects on reproductive function along with insulin sensitivity and luteinizing hormone (LH) release from the pituitary gland. In conclusion, this study demonstrates that dapagliflozin alleviated HFD-induced reproductive dysfunction independently of obesity, peripheral tissue insulin resistance, and systemic inflammation, suggesting its potential as a promising treatment for diet-related ovulation disorders.

Dapagliflozin increased pancreatic beta cell proliferation and insulinogenic index in mice fed a high-fat and high-sodium chloride diet.

People in Eastern Asia, including Japan, traditionally consume higher amounts of sodium chloride than in the United States and Western Europe, and it is common knowledge that impaired insulin secretion-rather than insulin resistance-is highly prevalent in Asian people who have diabetes mellitus. We previously reported that mice fed a high-fat and high-sodium chloride (HFHS) diet had a relatively lower degree of obesity than mice fed a high-fat diet, but had a comparatively impaired insulin secretion. Sodium-glucose cotransporter-2 (SGLT2) inhibitors have been shown to dampen down the sympathetic nervous system, which reportedly is activated by a high-sodium chloride diet. In this study, we examined the effects of dapagliflozin, a SGLT2 inhibitor, on glucose metabolism and insulin secretion in mice fed a HFHS diet. C57BL6/J mice were fed a HFHS diet for 6 weeks and subsequently divided into two treatment groups fed: (1) a HFHS diet mixed with dapagliflozin for up to 3 weeks (HFHS+Da) and (2) a HFHS diet without dapagliflozin (HFHS). Dapagliflozin improved glucose tolerance and the insulinogenic index accompanied by increased pancreatic beta cell proliferation. Furthermore, dapagliflozin decreased both the tyrosine hydroxylase-positive area in pancreatic islets and catecholamine excretion in urine. Our results suggest that dapagliflozin improved insulin secretion by suppressing sympathetic nerve activation in mice fed a HFHS diet.

Dapagliflozin attenuates skeletal muscle atrophy in diabetic nephropathy mice through suppressing Gasdermin D-mediated pyroptosis.

Skeletal muscle atrophy is a clinical concern in diabetic nephropathy, and without effective therapeutic approaches. Massive evidence has demonstrated that dapagliflozin, a sodium-glucose co-transporter 2 inhibitor can relieve diabetic nephropathy by inhibiting glucose re-absorption or podocyte pyroptosis. Nevertheless, whether dapagliflozin could treat skeletal muscle atrophy or the potential protection mechanism in diabetic nephropathy mice is unclear. The variety of approaches were used to assess the particular histology-associated characteristics, mRNA, and protein expression. These included examing the morphology of renal and skeletal muscle tissues through H&E staining, detecting mRNA and protein expression through real-time PCR and Western blot analysis, and monitoring fasting blood glucose levels by using Blood Glucose Monitor Test Kits. Dapagliflozin mitigated renal tissue injury with podocyte protein-nephrin and skeletal muscle atrophy effectively with mitochondrial-related proteins. Meanwhile, our research revealed that Casp3 was the target gene and dapagliflozin could decrease the expressions. Subsequently, we verified that dapagliflozin can effectively decrease canonical pyroptosis pathway proteins, which include Gasdermin D, NLRP3, Casp1, and ASC. Meanwhile, Palmitic acid (PA) induced Gasdermin E-N fragment (non-canonical pyroptosis protein) in C2C12 cells, and then released the inflammatory molecules such as IL-1β, IL-18, and NF-kappaB, which were suppressed by dapagliflozin treatment. Aside from that, dapagliflozin demonstrated a good binding affinity to the Casp3 and Gasdermin D protein, whereas it had a less binding affinity with NLRP3, Casp1, ASC, and Gasdermin E. At last, the Gasdermin D inhibitor can reverse the therapeutic effect of dapagliflozin. Dapagliflozin alleviates skeletal muscle atrophy in diabetic nephropathy mice, which is through the Gasdermin D-mediated canonical pyroptosis pathway.

Effects of dapagliflozin on heart rate variability, cardiac function, and short-term prognosis in early-onset post-myocardial infarction heart failure.

To investigate the effects of dapagliflozin, in addition to standard therapy, on heart rate variability (HRV), soluble growth stimulation expressed gene 2 protein (sST2), N-terminal pro B-type natriuretic peptide (NT-proBNP), and echocardiographic parameters in patients with early-onset post-myocardial infarction heart failure (HF). A total of 98 patients with early-onset post-myocardial infarction HF were enrolled and randomly divided into a control group (n = 48, receiving standard therapy) and an observation group (n = 50, receiving standard therapy plus dapagliflozin 10 mg daily). HRV, cardiac function, and echocardiographic parameters were measured at baseline and after 24 weeks of treatment. Short-term prognosis and adverse events were also monitored. Compared with the control group, the observation group showed significantly greater improvements in SDNN and SDANN (P < 0.05). Significant improvements were also observed in sST2 and NT-proBNP levels in the observation group compared to the control group (P < 0.05). Additionally, echocardiographic parameters, including EF, LVESD, LVEDD, IVST, LVMI, and E/e', showed greater improvement in the observation group (P < 0.05). The incidence of major adverse cardiovascular events was lower in the observation group (P < 0.05). Multivariate logistic regression model revealed that dapagliflozin use was independently associated with a reduced risk of MACE (OR = 0.265, 95% CI: 0.097-0.724, P = 0.010). Early administration of dapagliflozin 10 mg, in addition to standard therapy, can improve autonomic function, cardiac function, and short-term prognosis in patients with early-onset post-myocardial infarction heart failure.

Open-Label, Randomized, Controlled, Crossover Trial on the Effect of Dapagliflozin in Patients With ADPKD Receiving Tolvaptan

Open-Label, Randomized, Controlled, Crossover Trial on the Effect of Dapagliflozin in Patients With ADPKD Receiving Tolvaptan

Radiomics features of CMR LGE images may detect early myocardial effects of SGLT2 Inhibitor Dapagliflozin in diabetic patients without heart disease

Radiomics features of CMR LGE images may detect early myocardial effects of SGLT2 Inhibitor Dapagliflozin in diabetic patients without heart disease

Dapagliflozin treatment decreases visceral and subcutaneous adipose tissue: a systematic review and meta-analysis.

Sodium-glucose co-transporter-2 inhibitors (SGLT2i) have been shown to reduce visceral (VAT) and subcutaneous (SAT) adipose tissue. Although many systematic reviews have examined SGLT2i's effect on VAT and SAT, a focus analysis of dapagliflozin, one of the more commonly prescribe SGLT2i, has yet to been done. This study aims to determine the effect of dapagliflozin on reducing VAT and SAT in patients with chronic disease. SCOPUS, PubMed, EBSCO, and LILACS databases were searched until December 26, 2023. Heterogeneity was determined using Cochran's Q test and quantified using the inconsistency index. The random-effects model was used to calculate the pooled standardize difference in means (SDM) and 95% confidence intervals (95% CI). Duval and Tweedie trim and fill (DT), Egger's test, and Beggs-Muzamar's test were used to assess publication bias. PROSPERO: CRD42023426208. Twelve reports were included (treated = 299 and controls = 301). Overall, dapagliflozin treatment reduced VAT (SDM = -0.406, 95% CI: -0.526 to -0.286, p < 0.001) and SAT (SDM = -0.439, 95% CI: -0.601 to -0.278, p < 0.001). These results were stable as determined with a sensitivity analysis; however, there was potential publication bias. Two and three imputed studies were determined by the DT method for VAT and SAT, respectively. When stratified by pathology (obesity, T2D, and T2D/NAFLD), dapagliflozin treatment decreased VAT and SAT for all conditions. However, for specifically SAT, only when compared between T2D and T2D/NAFLD, T2D/NAFLD was associated with a twofold decrease (p = 0.003). Treatment with dapagliflozin resulted in a significant reduction in VAT and SAT in patients with obesity, T2D, or T2D/NAFLD. The online version contains supplementary material available at 10.1007/s13340-024-00765-y.

Dapagliflozin inhibits ferroptosis to improve chronic heart failure by regulating Nrf2/HO-1/GPX4 signaling pathway.

To study the effect of Dapagliflozin on ferroptosis in rabbits with chronic heart failure and to reveal its possible mechanism. Nine healthy adult male New Zealand white rabbits were randomly divided into Sham group (only thorax opening was performed in Sham group, no ascending aorta circumferential ligation was performed), Heart failure group (HF group, ascending aorta circumferential ligation was performed in HF group to establish the animal model of heart failure), and Dapagliflozin group (DAPA group, after the rabbit chronic heart failure model was successfully made in DAPA group). Dapagliflozin was given by force-feeding method. Echocardiography was used to assess cardiac function, HE staining to evaluate pathological changes in the heart, Prussia blue staining to observe iron ions in myocardial tissue, and enzyme-linked immunosorbent assay (ELISA) to determine serum levels of the inflammatory factors interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) at the end of week 12 and/or the end of week 16. The oxidative stress related indexes of malondialdehyde (MDA), superoxide dismutase (SOD) and superoxide dismutase (GSH-Px) in serum were quantitatively analyzed by colorimetry. Protein expression levels of nuclear factor E2-related factor 2(Nrf2), heme oxygenase-1(HO-1), glutathione peroxidase 4(Gpx4) were detected by Western blot. In animals with chronic heart failure, Dapagliflozin improved cardiomyocyte hypertrophy, degeneration and necrosis. Dapagliflozin increased serum GSH-Px and SOD levels and decreased IL-1β, IL-6, TNF-α and MDA levels (P < 0.05) in a rabbit model of heart failure. Dapagliflozin also decreased cardiac iron ion levels and increased Nrf2, HO-1 and GPX4 protein expression. Dapagliflozin can improve heart failure by inhibiting oxidative stress and ferroptosis, and its mechanism may be related to the regulation of Nrf2/HO-1/GPX4 signaling pathway.

Efficacy and Safety of Dapagliflozin Compared to Pioglitazone in Diabetic and Non-Diabetic Patients with Non-alcoholic Steatohepatitis: A Randomized Clinical Trial.

Non-alcoholic steatohepatitis (NASH) is a serious end-stage spectrum of non-alcoholic fatty liver disease (NAFLD) with associated high risk of hepatic and extrahepatic complications. Several studies showed the significant beneficial effect of dapagliflozin on body composition, hepatic and metabolic parameters on NAFLD/NASH patients. The study aimed to investigate the efficacy and safety of dapagliflozin in both diabetic and non-diabetic biopsy-proven NASH patients; compared to pioglitazone. This was a four-group, prospective, randomized, parallel, open label study in which 100 biopsy-proven NASH patients were selected, stratified to diabetics and non-diabetics and randomized with 1:1 allocation to either 30 mg pioglitazone or 10 mg dapagliflozin, once daily for 24 weeks. Histological evaluation, anthropometric measures, hepatic, metabolic biochemical markers, fibrosis non-invasive markers, quality of life (QOL) and medications adverse events were examined. Dapagliflozin showed a comparable histological effect to pioglitazone in both diabetic and non-diabetic patients (P>0.05). As assessed by transient elastography, it also showed a comparable effect on liver fibrosis grade improvement from baseline in diabetics (P=0.287) versus a significant superiority in non-diabetics (P=0.018). Dapagliflozin showed a significant superiority in all anthropometric measures (P<0.001) and QOL (P<0.05) among both diabetics and non-diabetics. There was a significant interaction between interventions and diabetes status on change from baseline of hepatic and metabolic panel collectively (P=0.023) in favor to dapagliflozin among diabetics. Compared to pioglitazone, dapagliflozin had a comparable effect histologically, superior effect biochemically among diabetics and superior effect on liver fibrosis, steatosis and insulin resistance among non-diabetics. The study was registered on clinicaltrials.gov, identifier number NCT05254626.

Effects of Empagliflozin and Dapagliflozin in alleviating cardiac fibrosis through SIRT6-mediated oxidative stress reduction

Sodium-glucose co-transport protein 2 (SGLT2) inhibitors, a novel category of oral hypoglycemic agents, offer a promising outlook for individuals experiencing heart failure with reduced ejection fraction. Evidence is emerging that highlights their potential in alleviating myocardial fibrosis and oxidative stress. However, the precise mechanisms through which SGLT2 inhibitors influence myocardial fibrosis induced by angiotensin II (Ang II) or transforming growth factor-β1 (TGF-β1) are not fully understood. This study aims to explore the intricate mechanisms by which SGLT2 inhibitors ameliorate myocardial fibrosis, particularly focusing on the nuanced interplay within the SIRT6 signaling pathway. Primary cardiac fibroblasts were isolated from the hearts of 1-3-day-old neonatal KM mice, were stimulated with Ang II or TGF-β1 to establish an in vitro model of myocardial fibrosis. Treatment with 10 µM Empagliflozin (EMPA) and Dapagliflozin (DAPA) significantly curtailed the proliferation of cardiac fibroblasts, substantially reduced collagen expression induced by Ang II/TGF-β1, and mitigated the phenotypic transformation and oxidative stress response. SIRT6, which is closely associated with myocardial fibrosis, demonstrated that the suppression its expression attenuated the protective effects of EMPA and DAPA against myocardial fibrosis and oxidative stress. Our findings suggest that SGLT2 inhibitors markedly decrease the Ang II/TGF-β1-induced transformation of cardiac fibroblasts to a myofibroblast phenotype by upregulating SIRT6 protein expression, thereby inhibiting oxidative stress and ameliorating myocardial fibrosis.

Possible Beneficial Effect of Dapagliflozin in Improvement of Dyspnea Scale (VAS and SA-NYHA Class) in Patients with Acute Decompensated Heart Failure (ADHF)

Heart failure (HF) is a condition in which the heart is unable to pump enough blood to meet the body's needs. Diuretics are the mainstay of acute heart failure therapy, especially intravenous loop diuretics. In this study, IV.furosemide (120mg/day) plus 10mg dapagliflozin tablet were used daily. The aim of the present study is to observe the Possible beneficial effect of dapagliflozin in the improvement of dyspnea scale (VAS and SA-NYHA Class) in patients with ADHF. Between October 2023 and April 2024, a study was conducted at AL- Nasiriyah Heart Center, in the coronary care unit (CCU), in , southern of Iraq. One hundred subjects, both male and female were enrolled in the study after describing the study's goals, gauging patient satisfaction, and getting informed consent from the subjects. 100 enrolled patients were divided into two groups: The control group (Group A) involved (50 patients), given IV.furosemide (120mg/day) and the studied group (Group B) involved (50 patients), given IV. furosemide (120 mg/day) plus 10mg dapagliflozin tablet daily. Then, it was the assessment of symptoms of dyspnea by Visual Analog Scale and SA-NYHA class. It was found that dyspnea scales (VAS and SA-NYHA Class ) for patients in both groups (A and B) at hospital admission were significantly improved after subsequent days of admission.

Advancing cardiovascular outcomes with dapagliflozin and sacubitril in post-acute myocardial infarction heart failure and type 2 diabetes mellitus.

Coronary heart disease and type 2 diabetes mellitus (T2DM) often co-occur, presenting substantial health risks, particularly following acute myocardial infarction (AMI). While percutaneous coronary intervention (PCI) is a prevalent treatment, complications such as microvascular dysfunction may lead to heart failure, necessitating additional therapies. This editorial examines the emerging roles of sacubitril/valsartan and sodium-glucose co-transporter 2 inhibitors in managing post-PCI. Recent research investigates the combined effects of dapagliflozin and telmisartan on myocardial microperfusion in post-AMI heart failure patients with T2DM. The findings suggest that this combination enhances myocardial microcirculation, improves cardiac function, and achieves better glycemic control, with a reduced incidence of major adverse cardiovascular events. Despite ongoing challenges, the integration of dapagliflozin and sacubitril/valsartan represents a significant advancement in post-AMI care. Further investigation in larger cohorts and more diverse patient populations is required to confirm its long-term clinical outcomes.

The Role of Dapagliflozin in the Modulation of Hypothermia and Renal Injury Caused by Septic Shock in Euglycemic and Hyperglycemic Rat Models.

Recent research has validated the efficacy of sodium-glucose cotransporter-2 inhibitors (SGLT2i) in reducing glucose levels and exerting a nephroprotective role. This study aimed to examine the impact of dapagliflozin in preventing sepsis-induced acute kidney injury (AKI) and related consequences. The study used both normal and diabetic rat models to investigate whether the effectiveness of dapagliflozin is influenced by glycemia levels. Normal and diabetic Wistar albino rats were treated with dapagliflozin for two weeks and then received a single dose of lipopolysaccharide (LPS). After sepsis induction, skin and deep body temperatures were recorded every two hours. Blood and kidneys were collected for analysis using histological examination and biochemical assays. Dapagliflozin attenuated the consequences of sepsis through mitigation of LPS-induced hypothermia and AKI in the normal and diabetic septic groups. Dapagliflozin regulated the serum levels of AKI markers, including creatinine and blood urea nitrogen, as well as ion levels. Dapagliflozin attenuated LPS-induced AKI through modulation of renal inflammation and oxidative stress, which showed well-abundant glomeruli. These results indicated the protective effect of dapagliflozin against LPS-induced hypothermia and AKI, which was likely unrelated to its glucose-lowering properties, as evidenced in the non-diabetic septic group. The outcomes suggest that dapagliflozin has a potential impact in preventing sepsis-induced hypothermia and AKI via modulation of inflammation and oxidative stress, irrespective of glycemic levels.