| Background and ObjectionWith the improvement of living standards,the incidence of two metabolic diseases,type 2 diabetes mellitus(T2DM)and hyperuricemia(HUA),has been increasing year by year.Moreover,T2DM and HUA are risk factors for each other,which seriously endangers human health.At present,although there are a variety of hypoglycemic drugs to choose from,some patients still cannot achieve ideal blood glucose control,and these drugs do not have a clear direct effect on lowering uric acid.The sodium-glucose cotransporter 2(SGLT2)inhibitor Dapagliflozin,is a well tolerated oral hypoglycemic agent that reduces glucose reabsorption by the kidney and increases urine glucose excretion by inhibiting SGLT2 in proximal tubule S1 of the kidney,and then reduce blood glucose.In addition,SGLT2 inhibitors can also reduce serum uric acid and increase the excretion rate of uric acid,which may be caused by the increased glucose level in urine,and D-glucose in urine inhibits the glucose transporter 9(GLUT9)in renal tubular epithelial cells to reduce the reabsorption of uric acid,thus increasing the excretion of uric acid and thereby reducing the level of serum uric acid.Benzbromarone is a commonly used uric acid excretion drug.By inhibiting the functions of urate-anion transporter 1(URAT1)and GLUT9 in proximal renal tubules,it increases the excretion of uric acid and reduces the serum uric acid in patients.At present,there are few related studies on the treatment of patients with T2DM and HUA by SGLT2 inhibitors.In this study,we evaluated the effect of Dapagliflozin on blood glucose and uric acid in patients with type 2 diabetes mellitus complicated with hyperuricemia,compared with Benzbromarone and conventional hypoglycemic treatment,and evaluated the safety of Dapaglifolzin in clinical application,so as to provide a reference for clinical treatment.Methods1.Participants and study design1.1 Participants Subjects were selected in our hospital endocrinology department from August 2017 to June 2019.Total 75 patients with type 2 diabetes and hyperuricemia were enrolled in our study which including 67 males(89.3%)and 8 females(10.7%).The subjects were randomly divided into three groups:original protocol maintenance group(Con group),Benzbromarone group(Ben group),and Dapagliflozin group(Dap group).Among them,there were 25 patients in Con group,with an average age of(55.2±12.0)years.24 patients were in Ben group,and 1 patient fell off due to the loss of follow-up,finally 23 patients completed the experiment with an average age of(51.5±11.5)years.26 patients were in Dap group,and 2 patients fell off due to adverse drug reactions,finally 24 patients completed the trial with an average age of(52.4±12.2)years.1.2 Study design All subjects were given a low-purine and diabetic diet.The Con group maintained the original hypoglycemic regimen,the Ben group was added with Benzbromarone capsule 50mg orally per day on the basis of the original hypoglycemic regimen,the Dap group was added with Dapagliflozin tablet 10mg orally per day on the basis of the original hypoglycemic regimen.All patients were followed up by telephone once a week.If gout attack was treated with colchicine and/or Non-steroidal Anti-inflammatory drugs,the dosage of drugs should be reduced or stopped if other intolerable adverse reactions occurred.2.Experimental Methods2.1 Test indicators Subjects were tested for body weight,fasting plasma glucose(FPG),2-hour plasma glucose(2hPG),glycosylated hemoglobin(HbAlc),serum creatinine(SCr),serum uric acid(SUA),24-hour urine creatinine(24hUcr),and 24-hour urine uric acid(24hUUA)before treatment and after 12 weeks of treatment.Body mass index(BMI),urinary uric acid excretion(UEua)and fraction excretion of uric acid(FEua)were calculated.Adverse reactions were also recorded.2.2 Judging adverse reactions Hypoglycemia,liver and kidney dysfunction,hypotension,genital infection,bladder cancer,gout attack,gastrointestinal discomfort,allergy and other adverse reactions occurred during medication were recorded according to the drug instructions.2.3 Statistical methods SPSS20.0 software was used for statistical analysis.Descriptive characteristics were expressed as mean±SD,One-way ANOVA were performed to assess three groups difference,and Paired Sample T Test was used for comparison between groups before and after treatment.The counting data were presented as number and percentage(%),and the comparison between groups was conducted using chi-square test.Spearman method was used to analyze the correlation between SUA reduction value and other indicators.P<0.05 was considered statistically significant.Results1.The characteristics between three groupsThe ratio of male to female in the three groups respectively was 22/3,22/1 and 21/3.There was no significant difference in age,height,weight,BMI,SUA,24hUUA,24hUcr,UEua,FEua,FPG,2hPG and HbAlc among the three groups(P>0.05).the difference of SCr among the three groups was statistically significant(P<0.05),SCr in the Ben group was higher than that in the Con group and the Dap group(P<0.05),and there was no statistically significant difference between the Con group and the Dap group(P>0.05).2.Comparison of weight-related indicators before and after treatment between three groupsCompared with before treatment,the body weight and BMI in Con group respectively decreased(0.3±4.3)kg and(0.1±1.4)kg/m2(P>0.05).Body weight and BMI in the Ben group respectively decreased(0.3±2.8)kg and(0.1±0.9)kg/m2(P>0.05).Body weight and BMI in the Dap group,respectively decreased(3.3±4.0)kg and(1.1±1.3)kg/m2(P<0.05).After treatment,there was no significant difference in body weight and BMI among the three groups(P>0.05).3.Comparison of uric acid related indicators before and after treatment between three groupsCompared with before treatment,Con group SUA decreased(49.33±89.32)umol/1(P<0.05),24hUUA decreased(264.51±2378.91)umol/d,UEua decreased(206.79±2081.95)umol d-1(1.73m2)-1,and FEua increased(1.15±2.65)%(P>0.05).Ben group SUA decreased(170.70±110.07)umol/1(P<0.05),while 24hUUA,UEua and FEua respectively increased(713.02±1284.88)umol/d,(617.76±1095.65)umol·d-1·(1.73m2)-1 and(8.09±6.31)%(P<0.05).Dap group SUA decreased(138.79±94.99)umol/1(it accounted for 28%of the baseline value and 81%of the reduction in SUA in the Ben group),and FEua increased(3.15±3.04)%(P<0.05),while 24hUUA and UEua respectively decreased(188.53±1379.99)umol/d and(174.42±1117.87)umol·d-1·(1.73m2)-1(P>0.05).After treatment,there was no significant difference in 24hUUA and UEua among the three groups(P>0.05).Compared with Con group,the difference of SUA between Ben group and Dap group was statistically significant(P<0.05),while the Ben group and Dap group was not statistically significant difference in SUA(P>0.05).Compared with the Ben group,the difference of FEua between Con group and Dap group was statistically significant(P<0.05),while the Con group and Dap group was not statistically significant difference in FEua(P>0.05).4.Comparison of blood glucose related indicators before and after treatment between three groupsCompared with before treatment,Con group FPG,2hPG and HbAlc respectively increased(0.01±2.41)mmol/l,(0.02±4.58)mmol/l and(0.27±0.69)%(P>0.05),Ben group FPG and HbAlc respectively decreased(0.76±2.86)mmol/l and(0.11±1.31)%(P>0.05),while 2hPG increased(2.08±3.15)(P<0.05).FPG,2hPG and HbAlc in Dap group respectively decreased(1.83±2.76)mmol/1,(3.84±2.89)mmol/1 and(1.06±1.65)%(P<0.05).After treatment,there was no significant difference in FPG and HbAlc among the three groups(P>0.05).Compared with Con group and Ben group,2hPG in Dap group was statistically significant difference(P<0.05),while the difference of 2hPG between Con group and Ben group was not statistically significant(P>0.05).5.Correlation analysisThe decrease value of SUA was negatively correlated with the decrease value of FEua,and the difference was statistically significant(r=-0.699,P<0.05).In addition,the decrease value of SUA was negatively correlated with the decrease value of 24hUUA and UEua,and positively correlated with the decrease value of body weight,BMI,FPG,2hPG and HbAlc(r=-0.241,-0.252,0.085,0.090,0.178,0.124,0.196,P>0.05),the differences were not statistically significant.6.Safety evaluationThere were two patients had nausea in Con group.In Ben group,there was One patient had gout attack.In Dap group,one patient had hematuria and one patient had itchy skin.And the difference between the three groups was no significant(χ2=0.31,P>0.05).Conclusion1.Under the condition that the original hypoglycemic drugs remained unchanged,the addition of Dapagliflozin could effectively reduce fasting plasma glucose,2-hour plasma glucose,glycosylated hemoglobin and body weight in patients with type 2 diabetes mellitus and hyperuricemia,the hypoglycemic and weight loss effects were better than those in the Benzbromarone group and the original protocol maintenance group.2.Dapagliflozin can reduce the serum uric acid level by 28%in patients with type 2 diabetes mellitus and hyperuricemia,with an effect equivalent to 81%of that of Benzbromarone,and its mechanism may be related to promoting uric acid excretion.3.Among the evaluation indexes of renal uric acid excretion,fraction excretion of uric acid is more reliable and accurate than 24-hour urine uric acid and urinary uric acid excretion. |
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