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BACKGROUND:Dapagliflozin,an inhibitor of sodium-glucose cotransporter 2,can delay the progression of atherosclerosis by regulating glucose metabolism,inhibiting inflammation and improving endothelial cell function. OBJECTIVE:To study the effect of dapagliflozin on cell pyroptosis and endothelial dysfunction induced by oxidized low-density lipoprotein. METHODS:Human umbilical vein endothelial cells were divided into a control group(no intervention),a model group(treated with oxidized low-density lipoprotein for 24 hours),and a dapagliflozin group(treated with oxidized low-density lipoprotein + dapagliflozin for 24 hours).Endothelial cell proliferation activity was measured by cell counting kit-8 assay.The levels of intercellular adhesion molecule 1,vascular cell adhesion molecule 1,and monocyte chemotactic protein-1 in cell supernatant were detected using ELISA.Nitric oxide level in the cells was detected by nitrate reductase assay.The pyroptosis rate and characteristics of endothelial cells were detected by Hoechst 33342/PI fluorescence co-staining and lactate dehydrogenase release assay.The protein expression levels of NLRP3,caspase-1,GSDMD,interleukin-1β,and interleukin-18 were detected by western blot assay. RESULTS AND CONCLUSION:(1)Oxidized low-density lipoprotein could cause pyroptosis and dysfunction of endothelial cells.(2)Compared with the control group,the level of nitric oxide and cell activity were decreased(P<0.05),while lactate dehydrogenase,intercellular adhesion molecule 1,vascular cell adhesion molecule 1,and monocyte chemotactic protein-1 levels were significantly increased in the model group(P<0.05).Compared with the model group,cell activity and nitric oxide levels significantly increased(P<0.05),but lactate dehydrogenase,intercellular adhesion molecule 1,vascular cell adhesion molecule 1,and monocyte chemotactic protein-1 levels were significantly diminished in the dapagliflozin group(P<0.05).(3)Compared with the model group,cell pyroptosis rate and the protein expression of pyroptosis factor NLRP3,caspase-1,GSDMD,interleukin-18 and interleukin-1β significantly reduced in the dapagliflozin group(P<0.05).(4)The results indicate that dapagliflozin inhibits oxidized low-density lipoprotein-induced endothelial pyroptosis and ameliorates endothelial cell dysfunction.
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Objective:To analyze and explore the effect of dapagliflozin on cardiac function,mitogen activated protein ki-nase(MAPK),inducible nitric oxide synthase(iNOS)and extracellular regulated protein kinase 1/2(ERK1/2)in patients with severe heart failure(SHF).Methods:A total of 122 SHF patients treated in our hospital were selected,randomly and equally divided into routine treatment group(received diuretic vasodilation-dominant basic therapy)and dapagliflozin group(received dapagliflozin based on routine treatment group).After three-month treatment,therapeutic effect,cardi-ac function,coronary hemodynamic indexes and therapeutic safety were compared between two groups.Results:The total effective rate of dapagliflozin group was significantly higher than that of routine treatment group(91.80％vs.77.05％,P=0.025).Compared with routine treatment group after treatment,there were significant rise in left ventricular ejection fraction(LVEF),stroke volume(SV),diastolic peak velocity(DPV),systolic peak velocity(SPV)and coronary blood flow(CBF),and significant reductions in QT interval dispersion(QTd),left ventricular end-diastolic diameter(LVEDd),coronary resistance(CR)and levels of MAPK[(46.79±7.02)ng/L vs.(39.38±5.82)ng/L],iNOS[(88.93±10.02)μmol/L vs.(79.61±9.04)μmol/L]and ERK1/2[(27.03±5.83)ng/L vs.(21.62±4.18)ng/L]in dapagliflozin group,P=0.001 all.There was no significant difference in incidence rate of adverse reactions between two groups,P=0.408.Conclusion:Dapagliflozin combined with diuretic and vasodilator therapy has a significant therapeutic effect on patients with severe heart failure,which can improve cardiac function and coronary hemodynamics,reduce the levels of MAPK,iNOS,and ERK1/2 with good safety.
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Objective To investigate the short-term efficacy of dapagliflozin in the treatment of non-diabetic patients with severe aortic stenosis after transcatheter aortic valve replacement(TAVR).Methods A total of 84 non-diabetic patients with severe aortic stenosis after TAVR who were admitted to Zhengzhou Cardiovascular Hospital from March 2019 to September 2022 were selected as research subjects.According to the postoperative treatment,the patients were divided into control group and observation group,with 42 patients in each group.Patients in both groups underwent TAVR.The patients in the control group were given routine treatments such as antiplatelet drugs,cardiac remodeling improvement drugs,and diuretics after TAVR;patients in the observation group were given dapagliflozin 10 mg daily for 6 months in addition to treatment in the control group.The left ventricular ejection fraction(LVEF),left ventricular end-systolic diameter(LVESD),left ventricular end-diastolic diameter(LVEDD),aortic valve peak gradient(AVPG)and aortic valve peak velocity(AVPV)of patients in the two groups were measured by using an ultrasound diagnostic instrument before surgery,3 days and 6 months after TAVR;before surgery and 6 months after the TAVR,low-density lipoprotein cholesterol(LDL-C)in serum of patients in the two groups was detected by direct measurement method,lipoprotein a[Lp(a)]level in serum was detected by latex agglutination reaction method,hypersensitive C-reactive protein(hs-CRP)level in serum was detected by rate scattering turbidimetry;the levels of N-terminal pro B-type natriuretic peptide(NT-proBNP),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α)and interleukin-1 β(IL-1 β)in serum were detected by using enzyme-linked immunosorbent assay;the glycated hemoglobin level of patients in the two groups was measured by ion exchange chromatography.Results There was no statistically significant difference in LVEF,LVESD and LVEDD of patients in the two groups before and 3 days after surgery(P＞0.05);after 3 days of surgery,the AVPG and AVPV of patients in the two groups were significantly lower than those before surgery(P＜0.05).Six months after surgery,the LVEF of patients in the two groups was significantly higher than that before and 3 days after surgery,while LVESD,LVEDD,AVPG and AVPV were significantly lower than those before and 3 days after surgery(P＜0.05).There was no statistically significant difference in LVEF,LVESD,LVEDD,AVPG and AVPV between the control group and the observation group before and 3 days after surgery(P＞0.05).After 6 months of surgery,the LVEF of patients in the observation group was significantly higher than that in the control group,while LVESD and LVEDD were significantly lower than those in the control group(P＜0.05);there was no statistically significant difference in AVPG and AVPV of patients between the observation group and control group(P＞0.05).Before surgery,there was no statistically significant difference in body mass index(BMI),LDL-C and Lp(a)of patients between the two groups(P＞0.05).Six months after surgery,the BMI,LDL-C and Lp(a)of patients in the two groups were significantly lower than those before surgery,and the BMI,LDL-C and Lp(a)of patients in the observation group were significantly lower than those in the control group(P＜0.05).Before surgery,there was no statistically significant difference in the hs-CRP,NT-proBNP,IL-6,TNF-α and IL-1 β of patients between the two groups(P＞0.05);six months after surgery,the hs-CRP,NT-proBNP,IL-6,TNF-α and IL-1 β of patients in the two groups were significantly lower than those before surgery,and the hs-CRP,NT-proBNP,IL-6,TNF-α and IL-lβ of patients in the observation group were significantly lower than those in the control group(P＜0.05).There was no statistically significant difference in glycated hemoglobin of patients between the two groups before and six months after surgery(P＞0.05),and no statistically significant difference in glycated hemoglobin of patients in the two groups six months after surgery compared with that before surgery(P＞0.05).Conclusion Dapagliflozin can effectively improve cardiac structural remodeling,regulate lipid metabolism,reduce the expression of inflammatory factors and promote the recovery of heart function in non-diabetic patients with severe aortic stenosis after TAVR.
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Objective To investigate the effect of Dapagliflozin on high glucose-induced podocyte proliferation and apoptosis through p38 mitogen-activated protein kinase(p38 MAPK)pathway.Methods Human glomerular podocytes(HGPC)were divided into control(Con)group,low/medium/high D-glucose(Glu 10,Glu 20,Glu 30)group,high glucose(HG)group,low/medium/high concentration Dapagliflozin(HG+Dap 12.5,HG+Dap 25,HG+Dap 50)group,Dapagliflozin(HG+Dap)group,inhibitor(HG+ SB 203580)group,Dapagliflozin + inhibitor(HG+Dap+SB 203580)group and Dapagliflozin + activator(HG+Dap+C16-PAF)group.After 24 hours of intervention,the cell viability,proliferation rate,apoptosis rate and levels of related factors were tested.Results Compared with Con group,IL-1β,TNF-α,apoptosis rate,Caspase-3 mRNA and protein expression,p53,p-p38 MAPK protein expression were increased(P＜0.05),while cell proliferation rate,Cyclin D1 mRNA and protein expression were decreased in HG group(P＜0.05).Compared with HG group,the proliferation rate,Cyclin D1 mRNA and protein expression were increased(P＜0.05),while IL-1β,TNF-α,apoptosis rate,Caspase-3 mRNA and protein expression,p53,p-p38 MAPK protein expression were decreased in the HG+Dap and HG+SB 203580 groups(P＜0.05).Compared with HG+Dap group,cell proliferation rate,Cyclin D1 mRNA and protein expression were increased(P＜0.05),while IL-1β,TNF-α,apoptosis rate,Caspase-3 mRNA and protein expression,p53,p-p38 MAPK protein expression were decreased in HG+Dap+SB 203580 group(P＜0.05).In HG+Dap+C16-PAF group,IL-1β,TNF-α,apoptosis rate,Caspase-3 mRNA and protein expression,p53,p-p38 MAPK protein expression were increased(P＜0.05),while cell proliferation rate,Cyclin D1 mRNA and protein expression were decreased(P＜0.05).Conclusion Dagagliflozin can promote HGPC proliferation and inhibit apoptosis and inflammation in high D-glucose environment,and its mechanism may be related to the inhibition of p38 MAPK pathway signal transduction.
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As a new hypoglycemic drug,Dapagliflozin has attracted much attention because of its unique hypoglycemic mechanism. It has been used in many studies on type 2 diabetes mellitus,but the application of type 1 diabetes mellitus(T1DM)in the eastern population is rare. This article uses Dapagliflozin through a case of obese T1DM to provide new ideas for the treatment of T1DM.
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Objective To investigate the effect of dapagliflozin on myocardial work and energy metabolism in patients with heart failure with reduced ejection fraction(HFrEF)without type 2 diabetes mellitus(T2DM).Methods Patients with HFrEF without T2DM who visited Wuzhou People's Hospital from January 2021 to January 2022 were randomly divided into conventional group and dapagliflozin group(conventional treatment+dapagliflozin).After treatment(12 months),myocardial work[global work index(GWI),global constructed work(GCW),global wasted work(GW),and global work efficiency(GWE)],energy metabolism[(free fatty acids(FFA)and β-hydroxybutyric acid(β-HB)],traditional cardiac function[left ventricular end-diastolic diameter(LVEDD),left ventricular end-systolic diameter(LVESD),and left ventricular ejection fraction(LVEF)],clinical efficacy,prognosis[mortality,rehospitalization,and incidence of major adverse cardiovascular events(MACE)]and adverse reactions were compared between the two groups.Results A total of 128 patients with HFrEF without T2DM were enrolled,including 63 patients in the dapagliflozin group and 65 patients in the conventional group.After treatment,the LVEDD,LVESD,GWW,NT-pro BNP in the dapagliflozin group was significantly lower than that in the conventional group(P＜0.05),while the LVEF,GWI,GCW,GWE,β-HB acid and FFA were significantly higher than those in the conventional group(P＜0.05).The total effective rate and hypoglycemia rates in the dapagliflozin group were significantly higher than those in the conventional group(P＜0.05),and the rehospitalization rate and MACE rate were significantly lower than those in the conventional group(P＜0.05).There were no significant differences in mortality,renal adverse events,urinary tract infections and gastrointestinal symptoms between the two groups(P＞0.05).Conclusion Dapagliflozin has significant clinical efficacy in patients with HFrEF without T2DM,which can increase the serum levels of FFA and ketones,improve effective work,and reduce ineffective work,but it is necessary to be vigilant against hypoglycemia.
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@#Objective To investigate the protective effect of dapagliflozin on kidney and the expression of AMP-activated protein kinase(AMPK)/mammalian target of rapamycin(mTOR)signaling pathway in diabetic nephropathy(DN)rats.Methods A total of 40 SPF Wistar male rats were randomly divided into normal group,model group,low-dose group and high-dose group,with 10 rats in each group.After the DN model was successfully prepared,the rats in normal group were given normal diet + normal saline by gavage,the rats in model group was given high sugar and high fat feed + normal saline by gavage,the rats in low-dose group was given high sugar and high fat feed+1mg/(kg·d)of dapagliflozin by gavage,the rats in high-dose group was given high sugar and high fat feed+10mg/(kg·d)of dapagliflozin by gavage.Rats in each group were continuously gavaged for 12 weeks.Renal function indexes,renal pathological changes,p-AMPK and p-mTOR protein expression,collagen type Ⅰ(COL Ⅰ),collagen type Ⅳ(COL Ⅳ)and fibronectin(FN)of all groups were compared.Results Blood urea nitrogen(BUN),serum creatinine(SCr),24h urinary protein quantity,p-mTOR protein expression,COL Ⅰ,COL Ⅳ and FN levels of rats in model group,low-dose group and high-dose group were significantly higher than those in normal group,and p-AMPK protein expression was significantly lower than that of normal group(P<0.05).BUN,SCr,24h urinary protein quantity,p-mTOR protein expression,COL Ⅰ,COL Ⅳ and FN levels of rats in low-dose group and high-dose group were significantly lower than those in model group,while p-AMPK protein expression was significantly higher than that in model group(P<0.05).BUN,SCr,24h urinary protein quantity,p-mTOR protein expression,COL Ⅰ,COL Ⅳ and FN levels in high-dose group were significantly lower than those in low-dose group,and p-AMPK protein expression was significantly higher than that in low-dose group(P<0.05).Conclusion Dapagliflozin has a good kidney protection effect on DN rats,and its mechanism may be related to the regulation of AMPK/mTOR signaling pathway.
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Aim: To provide a pooled effect of sodium-glucose cotransporter-2 inhibitors (SGLT2i) on cardiovascular outcomes in patients with heart failure with preserved ejection fraction (HFpEF: _x0001_50%) or/and mildly reduced EF (HFmrEF: 41e49%) regardless of baseline diabetes. Methods: We systemically searched PubMed/MEDLINE, Embase, Web of Science databases and clinical trial registries using appropriate keywords till August 28, 2022, to identify randomized controlled trials (RCTs) or post-hoc analysis of RCTs, reporting cardiovascular death (CVD) and/or urgent visits/hospitalization for heart failure(HHF) in patients with HFmrEF/HFpEF receiving SGLTi vs. placebo. Hazard ratios (HR) with 95% confidence intervals (CI) for outcomes were pooled together using generic inverse variance method with fixed-effects model. Results: We identified six RCTs, pooling data retrieved from 15,769 patients with HFmrEF/HFpEF. Pooled analysis showed that compared to placebo, SGLT2i use was significantly associated with improved CVD/ HHF outcomes in HFmrEF/HFpEF (pooled HR 0.80, 95% CI: 0.74, 0.86, p < 0.001, I 2 ¼ 0%). When separately analyzed, benefits of SGLT2i remained significant across HFpEF (N ¼ 8891, HR 0.79, 95% CI: 0.71, 0.87, p < 0.001, I 2 ¼ 0%) and HFmrEF (N ¼ 4555, HR 0.77, 95% CI: 0.67, 0.89, p < 0.001, I 2 ¼ 40%). Consistent benefits were observed also in HFmrEF/HFpEF subgroup without baseline diabetes (N ¼ 6507, HR 0.80, 95% CI: 0.70, 0.91, p < 0.001, I 2 ¼ 0%). Sensitivity analysis including the DELIVER and EMPEROR-Preserved trials found a trend towards significant beneficial effects on CV deaths with no heterogeneity (HR 0.90, 95% CI: 0.79, 1.02, p ¼ 0.08, I 2 ¼ 0%). Conclusions: This meta-analysis established the place of SGLT2i as a foundational therapy among patients with HF with preserved and mildly reduced EF regardless of diabetes.
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Objective To investigate the effect of dapagliflozin on cardiac function and major adverse cardiac events(MACE)in elderly patients with heart failure after acute myocardial infarction.Methods The clinical data of 59 elderly patients with heart failure after acute myocardial infarction,treated in Liyuan Hospital,Tongji Medical College,Huazhong University of Science and Technology from May 2021 to February 2022,were collected and retrospectively analyzed.The objects were divided into control group(n=29)and dapagliflozin group(n=30)according to whether they took dapagliflozin during routine treatment.The cardiac function indexes[left vetricular ejection fraction(LVEF),left ventricular end-diastolic diameter(LVEDD),left ventricular end-systolic diameter(LVESD)]and the level of N-terminal pro-brain natriuretic peptide(NT-proBNP);as well as clinical total effective rate,Killip grading and MACE occurrence were detected and compared at discharge and within 6 months after discharge.Results At discharge and within 6 months'treatment,the levels of LVEF increased(P<0.05),and of LVEDD,LVESD and NT-proBNP decreased(P<0.05)in the two groups than those before treatment.The level of LVEF in the dapagliflozin group was higher(P<0.05),and the levels of LVEDD,LVESD and NT-proBNP were lower in dapagliflozin group(P<0.05)than those in control group.There was no statistical difference in the clinical total effective rate between the two groups(86.7%vs.65.5%,P>0.05)at discharge;The clinical total effective rate of dapagliflozin group was 93.3%,which was higher than control group of 62.1%within 6 months'treatment(P<0.05).Before treatment,at discharge and within 6 months'treatment,there was no statistical difference in the Killip classification between the two groups(P≥0.05).The incidence of MACE in dapagliflozin group was lower than that in control group within 6 months'treatment(P<0.05).Conclusion Compared with conventional anti heart failure therapy,combined with dapagliflozin can improve the cardiac function and prognosis,reduce the incidence of MACE of patients with heart failure after acute myocardial infarction.
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Objective:To analyze the efficacy and safety of dapagliflozin combined with metformin in the treatment of type 2 diabetes.Methods:A prospective research method was adopted. A total of 60 patients with type 2 diabetes who were treated in Huainan Chaoyang Hospital from January 2019 to December 2021 were collected as research objects, and the above patients were divided into the observation group (30 cases) and the control group (30 cases) according to the random number table method. After admission, they were treated with oral metformin sustained-release tablets combined with exercise and diet control. On this basis, the observation group was treated with dapagliflozin, while the control group was treated with glimepiride. The blood glucose-related indexes after 3 months of treatment, blood lipid indexes after 1 month of treatment, and adverse reactions were compared between the two groups of patients.Results:After 3 months of treatment, the fasting blood glucose (FBG), 2 h postprandial blood glucose (2 h PBG) and glycosylated hemoglobin (HbA 1c) of the two groups were significantly lower than those before treatment, observation group: (6.60 ± 1.01) mmol/L vs. (7.76 ± 1.82) mmol/L, (10.43 ± 2.74) mmol/L vs. (14.05 ± 3.84) mmol/L, (5.90 ± 1.56)% vs. (8.46 ± 2.07)%; control group: (6.77 ± 0.95) mmol/L vs. (7.82 ± 1.38) mmol/L, (10.17 ± 2.23) mmol/L vs. (14.01 ± 2.63) mmol/L, (6.14 ± 1.51)% vs. (8.73 ± 1.58)% ( P<0.05), but there was no difference in FBG, 2 h PBG and HbA 1c between the two groups ( P>0.05). The total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) in the observation group were significantly lower than those in the control group: (5.02 ± 0.98) mmol/L vs. (5.71 ± 0.77) mmol/L, (2.81 ± 0.69) mmol/L vs. (3.39 ± 0.87) mmol/L ( P<0.05). There was no difference in adverse reactions ( P>0.05). Conclusions:For patients with type 2 diabetes mellitus, on the basis of metformin sustained-release therapy, whether combined with dapagliflozin or glimepiride therapy has good hypoglycemic effect, but dapagliflozin has more advantages in improving blood lipids.
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Objective:To investigate the clinical effect of dapagliflozin combined with metformin on type 2 diabetes mellitus (T2DM).Methods:A total of 100 patients with T2DM who received treatment in The Second People's Hospital of Hefei from June 2019 to May 2021 were included in this study. They were randomly divided into a control group ( n = 50) and an experimental group ( n = 50). The control group was treated with metformin, and the experimental group was treated with dagglitazin combined with metformin. All patients were treated for 3 months. Blood glucose index, blood lipid level, and the incidence of adverse reactions were compared between the two groups. Results:After treatment, fasting blood glucose, 2-hour post-prandial blood glucose, and glycosylated hemoglobin in the experimental group were (5.56 ± 0.37) mmol/L, (8.32 ± 0.23) mmol/L, and (6.17 ± 0.26)% respectively, which were significantly lower than (6.96 ± 0.48) mmol/L, (9.58 ± 0.39) mmol/L, and (7.27 ± 0.26)% respectively in the control group ( t = 3.59, 6.92, 5.03, all P < 0.05). The total cholesterol and triglyceride in the experimental group were (3.58 ± 0.53) mmol/L and (1.25±0.26) mmol/L, respectively, which were significantly lower than (4.94 ± 0.58) mmol/L and (1.93 ± 0.18) mmol/L in the control group ( t = 3.16, 4.25, both P < 0.05). There was no significant difference in the incidence of adverse reactions between the two groups ( P > 0.05). Conclusion:Dapagliflozin combined with metformin can effectively control blood glucose and blood lipid in T2DM patients without increasing adverse reactions.
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【Objective】 To investigate the role and mechanism of dapagliflozin (Dapa), a sodium glucose co-transporter 2 inhibitor, in acute liver injury. 【Methods】 Eight-week-old C57BL6/J mice were given a single intraperitoneal injection of CCl4 to induce acute liver injury. The mice were preventively given 5 mg/kg Dapa by gavage 24 h and 2 h before CCl4 injection, while those in the control group were given an equal volume of solvent gavage. After 24 h, the mice were anesthetized and sacrificed. H&E staining, plasma biochemistry, RT-qPCR, and Western blotting were used to detect the severity of liver injury and the expressions of macrophage-related genes. 【Results】 In the CCl4 group, hepatic infiltration of inflammatory cells increased, and liver and renal functions significantly deteriorated, which was further aggravated by Dapa. CCl4 could promote the expressions of M1 macrophages and fibrosis-related genes in the liver, but reduce those of M2 and antioxidant-related genes, and the latter was further inhibited by Dapa. In addition, the protein expression of arginase 1 decreased and that of SGLT2 increased after Dapa intervention, while NF-κB pathway did not change significantly, suggesting that Dapa might directly affect the energy metabolism homeostasis in the liver and aggravate acute liver injury induced by CCl4. 【Conclusion】 Dapa can exacerbate hepatic and renal damage in acute stage of liver injury, inhibit macrophages M2 polarization, and aggravate oxidative stress and inflammatory injury induced by CCl4.
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【Objective】 To observe the clinical effect of combination therapy of sacubitril valsartan and dapagliflozin in heart failure with reduced ejection fraction (HFrEF) and non-diabetes patients. 【Methods】 This study involved 96 patients with HFrEF and non-diabetes. The patients were randomly divided into control group (50 cases) and observation group (46 cases). On the basis of routine treatment, the control group was treated with sacubitril valsartan, while the observation group was treated with sacubitril valsartan and dapagliflozin. After 1-month and 6-month treatment, we monitored blood pressure, N-terminal pro brain natriuretic peptide (NT-proBNP), high sensitivity troponin T (cTnT), fasting blood glucose (FBG), glycosylated hemoglobin (HbA1c), left ventricular ejection fraction (LVEF), left ventricular end diastolic diameter (LVEDd), left atrial diameter (LAD), left ventricular posterior wall thickness (LVPW), Minnesota soda heart failure life quality score (MLHFQ), the incidence of rehospitalization and death, and major adverse cardiovascular events (MACE) in the two groups. 【Results】 After 6 months, systolic blood pressure, cTnT, NT-proBNP, LVEDd, LVPW, and LAD of the observation group were significantly decreased compared with the control group (P0.05). 【Conclusion】 The combination treatment of sacubitril valsartan and dapagliflozin on HFrEF and non-diabetes patients can significantly improve cardiac function, inhibit myocardial remodeling, reduce the incidence of MACE, and improve the prognosis.
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Aim To investigate the effect of dapagliflozin on the small conductance calcium-activated potassium channel 2 (SK2 channel) protein in the myocardium of diabetic rats and its possible mechanism of action. Methods In vivo: type 2 diabetes model was established by high-glucose and high-fat diet combined with intraperitoneal injection of low-dose streptozotocin (35 mg
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AIM: To explore the pharmacokinetic interactions between sorafenib and dapagliflozin in rats and to provide some theoretical basis for the rational clinical use of the two drugs. METHODS: An ultra -performance liquid chromatography-tandem mass spectrometry (UPLC / MS / MS) method was developed for the simultaneous determination of sorafenib and dapagliflozin. Male SD rats were randomly divided into 5 groups (6 rats in each group), including 100 mg / kg sorafenib group, 0.5 mg / kg dapagliflozin group, 1 mg / kg dapagliflozin group, and 100 mg/kg sorafenib combined with 0.5 mg/kg dapagliflozin group and 100 mg/kg sorafenib combined with 1 mg / kg dapagliflozin group, for sorafenib and dapagliflozin drug interaction study. All samples were analyzed using a validated UPLC/ MS/MS method, and the main pharmacokinetic parameters were calculated by compartment model. RESULTS: 1 mg/kg dapagliflozin increased the C
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AIM: To investigate the effect of dapagliflozin on myocardial injury in type 1 diabetes mice and its mechanism. METHODS: Normal C57BL / 6J male mice were randomly divided into normal control group (Control), diabetes cardiomyopathy group (DCM) and dapagliflozin group (DAPA). The model of diabetes was induced by streptozotocin (STZ) and given maintenance feed. DAPA group was given 10 mg · kg
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Objective:To investigate the effect of dapagliflozin on cognitive function in middle-aged and elderly type 2 diabetes mellitus patients and related factors.Methods:This was a retrospective study. A total of 200 patients who were hospitalized in the Department of Endocrinology, the Second Affiliated Hospital of Anhui Medical University from August 2021 to August 2022 were recruited randomly. They were divided into the dapagliflozin group and control group. Clinical data were collected; plasma levels of β-amyloid protein(Aβ) 40 and Aβ42 were measured. The Montreal cognitive assessment(MoCA) and the mini-mental state examination(MMSE) were employed to assess cognitive function in both groups. Based on MoCA scores, patients in the dapagliflozin group were further categorized into mild cognitive impairment(MCI) and non-MCI subgroups. Differences among groups were analyzed and compared using t-test, χ2 test, and Mann-Whitney U test, and multivariable logistic regression was used to identify relevant factors associated with cognitive impairment in diabetes patients. Results:Compared to the control group, the dapagliflozin group exhibited significant increases in MMSE and MoCA scores, estimated glomerular filtration rate, and plasma concentration Aβ40(all P<0.05); And the incidence of MCI, homeostasis model assessment for insulin resistance(HOMA-IR), total cholesterol, triglycerides, urine albumin creatine ratio, plasma Aβ42, and Aβ42/Aβ40 ratio were significantly decreased(all P<0.05). Compared with the MCI subgroup, duration of dapagliflozin treatment in the non-MCI subgroup were significantly increased( P<0.05); There were statistically significant decreased in the non-MCI subgroup in age, systolic blood pressure, fasting plasma C-peptide, and HOMA-IR(all P<0.05). Multivariable logistic regression analysis showed that duration of dapagliflozin treatment was a protective factor for cognitive dysfunction( OR=0.322, 95% CI 0.150-0.692, P=0.004) and the age and HOMA-IR were risk factors( OR=1.109, 95% CI 1.014-1.212, P=0.023; OR=3.376, 95% CI 1.276-8.931, P=0.014). Conclusion:Dapagliflozin may improve cognitive function and significantly reduce the incidence of MCI in middle-aged and elderly patients with type 2 diabetes mellitus, possibly associated with the improvement of insulin resistance.
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Objective:To investigate the efficacy of dapagliflozin combined with tirofiban in patients with type 2 diabetes mellitus complicated with coronary heart disease.Methods:A total of 120 patients with type 2 diabetes mellitus and coronary heart disease treated in Fuyang People′s Hospital from January to August 2022 were prospectively selected as subjects. According to different treatment methods, they were divided into control group and experimental group. The control group was treated with tirofiban, and the experimental group was treated with dapagliflozin combined with tirofiban. The efficacy and safety of treatments between the two groups were compared.Results:After 3 months of treatment, fasting plasma glucose (FPG), 2 h postprandional blood glucose (2 h PG), glycated hemoglobin (HbA 1c), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), D-dimer (D-D) and fibrinogen (FIB) levels in 2 groups were decreased compared with before treatment:experimental group: (7.33 ± 1.77) mmol/L vs. (9.45 ± 2.05) mmol/L, (10.33 ± 2.07) mmol/L vs. (13.57 ± 2.88) mmol/L, (7.22 ± 1.28) % vs. (9.25 ± 1.78) %, (1.98 ± 0.29) mmol/L vs. (6.05 ± 1.24) mmol/L, (2.95 ± 0.37) mmol/L vs. (4.35 ± 0.76) mmol/L, (0.78 ± 0.23) mg/L vs. (1.85 ± 0.79) mg/L, (2.57 ± 0.37) g/L vs. (7.15 ± 1.36) g/L, control group: (8.21 ± 1.85) mmol/L vs. (9.68 ± 2.17) mmol/L, (11.78 ± 2.26) mmol/L vs. (13.89 ± 3.02) mmol/L, (8.25 ± 1.36) % vs. (9.37 ± 1.86) %, (2.77 ± 0.42) mmol/L vs. (6.08 ± 1.22) mmol/L, (3.84 ± 0.44) mmol/L vs. (4.27 ± 0.72) mmol/L, (1.34 ± 0.52) mg/L vs. (1.81 ± 0.72) mg/L, (5.25 ± 0.84 ) g/L vs. (7.11 ± 1.28) g/L, the differences were statistically significant ( P< 0.05). The levels of FPG, 2 h PG, HbA 1c, TC, LDL-C, D-D and FIB between the two groups were statistically significant ( P<0.05). High density lipoprotein cholesterol (HDL-C) level, left ventricular ejection fraction (LVEF), cardiac blood transfusion volume (CO), stroke output (SV), thrombin time (TT) and partially activated prothrombin time (APTT) were all increased: experimental group: (1.76 ± 0.30) mmol/L vs. (1.07 ± 0.28) mmol/L, (68.64 ± 12.91) % vs. (45.05 ± 12.24) %, (4.88 ± 0.91) L/min vs. (3.95 ± 1.12) L/min, (53.66 ± 5.43) ml/min vs. (43.27 ± 4.88) ml/min, (31.83 ± 4.39) s vs. (23.25 ± 3.44) s, (13.85 ± 2.17) s vs. (10.75 ± 1.56) s, control group: (1.43 ± 0.26) mmol/L vs. (1.06 ± 0.24) mmol/L, (60.37 ± 11.86) % vs. (45.42 ± 12.41) %, (4.37 ± 0.84) L/min vs. (4.17 ± 1.16) L/min, (47.86 ± 5.27) ml/min vs. (43.36 ± 4.94) ml/min, (27.24 ± 3.91) s vs. (23.78 ± 3.62) s, (12.74 ± 1.94) s vs. (10.89 ± 1.78) s, the differences were statistically significant ( P<0.05). There were significant differences in HDL-C, LVEF, CO, SV, TT and APTT between the two groups ( P<0.05). The incidence of adverse reactions in experimental group was lower than that in control group during treatment: 5.00% (3/60) vs. 16.67% (10/60), and the difference was statistically significant ( P<0.05). Conclusions:Dapagliflozin combined with tirofiban in the treatment of patients with type 2 diabetes mellitus complicated with coronary heart disease has obvious curative effect, and can improve blood glucose and blood lipid levels, coagulation function and cardiac function, with high safety.
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Objective:To investigate the efficacy of dapagliflozin in patients with diabetic nephropathy.Methods:A total of 82 patients with early diabetic nephropathy who were treated in Wuhu No.1 People′s Hospital from January 2020 to December 2021 were selected as the research objects, and they were divided into the conventional group (41 cases) and the dapagliflozin group (41 cases) according to the random number table method. The patients in the conventional group were given original hypoglycemic treatment and the patients in the dapagliflozin group were given dapagliflozin treatment on the former basis, the patients in the two groups were treated for 12 weeks. The levels renal function index, blood glucose index, glomerular filtration index and the occurrence of adverse reactions during the treatment period were compared between the two groups.Results:After treatment, the total clinical effective rate in the dapagliflozin group was higher than that in the conventional group: 95.12%(39/41) vs. 78.05%(32/41), there was statistical difference ( χ2 = 4.96, P<0.05). The levels of urine albumin/creatinine (UACR), blood urea nitrogen (BUN) , serum creatinine (SCr), fasting blood glucose (FPG), 2 h postprandial blood glucose (2 h PG), glycosylated hemoglobin (HbA 1c), cystatin C (Cys-C) in the dapagliflozin group were lower than those in the conventional group: (49.73 ± 11.65) mg/g vs. (67.26 ± 10.04) mg/g, (6.96 ± 0.54) mmol/L vs. (7.25 ± 0.48) mmol/L, (76.82 ± 2.86) μmol/L vs. (78.59 ± 3.06) μmol/L, (8.58 ± 0.18) mmol/L vs. (8.80 ± 0.32) mmol/L, (8.03 ± 0.42) mmol/L vs. (8.56 ± 0.44) mmol/L, (7.06 ± 0.57)% vs. (7.52 ± 1.06)%, (1.47 ± 0.50) mg/L vs. (1.84 ± 0.55) mg/L, there were statistical differences ( P<0.05). The level of glomerular filtration rate (GFR) between the two groups had no significant differences ( P>0.05). The incidence of total adverse reactions in dapagliflozin group was lower than that in control group: 7.32%(3/41) vs. 24.39%(10/41), there was statistical difference ( P<0.05). Conclusions:Dapagliflozin has a good effect in the treatment of patients with early diabetic nephropathy. It can lower glucose, improve Cys-C, reduce urinary microalbumin and protect renal function.
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Objective To investigate the effect of dapagliflozin on blood pressure variability(BPV)and left ventricular mass index(LVMI)in patients with type 2 diabetes mellitus(T2DM)and hypertension.Methods Patients with T2DM complicated with hypertension admitted to Lishui Central Hospital from August 2021 to August 2022 were selected as the study subjects,and were treated with conventional treatment(control group)and dapagliflozin treatment(test group),respectively.The changes of BPV index,LVMI,blood glucose level and the incidence of adverse reactions were compared between the two groups.Results A total of 94 patients with T2DM and hypertension were included in the study,including 47 patients in the test group and 47 in the control group.The 24-hour diastolic blood pressure(DBP),24-hour systolic blood pressure(SBP),24-hour systolic standard deviation(SSD),24-hour diastolic standard deviation(DSD),fasting blood glucose(FBG),2-hour blood glucose(PG),glycated hemoglobin glycosylated hemoglobin(HbA1c),body mass index(BMI)and LVMI of the patients with T2DM and hypertension were significantly decreased in the two groups(P<0.05),and the 24-hour SBP,24-hour DBP,24-hour SSD,24-hour DSD,FPG,2-hour PG,HbA1c,BMI and LVMI in the test group were lower than those in the control group(P<0.05).The total incidence of adverse reactions between the test group and the control group was 10.64% and 4.26% ,respectively,and the difference was not statistically significant(P>0.05).Conclusion Dapagliflozin can reduce LVMI and improve BPV and blood glucose levels in patients with T2DM and hypertension,and has a good safety profile.