The Effect Of Dapagliflozin Combined With Metformin On Insulin Resistance And Sex Hormone Levels In T2DM Patients With PCOS

Objective:To observe the changes of glucolipid metabolism,insulin resistance and sex hormone levels in patients with type 2 diabetes mellitus（T2DM）complicated with polycystic ovary syndrome（PCOS）treated with dapagliflozin or pioglitazone combined with metformin,to further reveal the effect of dapagliflozin on insulin resistance and sex hormone in T2DM patients with PCOS in addition to hypoglycemia.Methods:A total of 120 patients with T2DM complicated with PCOS who were admitted to the First Hospital of Lanzhou University from January 2018 to December2021 were enrolled in this study.On the basis of diabetes health education,diet and exercise,metformin alone was treated as metformin group,pioglitazone combined with metformin as pioglitazone group,and dapagliflozin combined with metformin as dapagliflozin group,and there were 40 cases in each group.General clinical data,glucose and lipid metabolism indexes,insulin resistance indexes of all patients were collected in detail:fasting insulin（FINS）,insulin resistance index（HOMA-IR）,isletβcell function index（HOMA-β）,insulin sensitivity index（HOMA-ISI）,fasting blood glucose/fasting insulin（G₀/I₀）and sex hormone:Testosterone（T）,androstenedione（A）and dehydroepiandrosterone（DHEA）.Spearman correlation analysis and multiple linear regression analysis were used to explore the related factors affecting insulin resistance and sex hormone levels in T2DM patients with PCOS.Results:1.Comparison of baseline data among three groups:there were no significant differences in age,course of diabetes,height,weight,BMI,SBP,DBP,FBG,2h BG,Hb A1c,FINS,TC,TG,LDL-C,HDL-C,T,A and DHEA among three groups（P>0.05）.2.Comparison of clinical data in the three groups before and after treatment:after treatment,the body weight,BMI,SBP and DBP were significantly reduced in three groups（P<0.01）,but there was no significant difference in DBP among the three groups（P>0.05）.Compared with metformin group,body weight and BMI of pioglitazone group after treatment had no significant difference（P>0.05）,SBP was significantly decreased（P<0.01）.After treatment,the body weight,BMI and SBP of dapagliflozin group were lower than those of metformin group and pioglitazone group（P<0.05）.3.Comparison of glucolipid metabolism indexes in three groups before and after treatment:FBG,2h BG and Hb A1c in three groups were significantly decreased after treatment（P<0.01）;FBG,2h BG and Hb A1c in pioglitazone group and dapagliflozin group were lower than those in metformin group（P<0.05）,and the decrease in dapagliflozin group was more significant（P<0.05）.In metformin group,TG and LDL-C decreased（P<0.05）,while TC and HDL-C did not change significantly（P>0.05）.TC,TG and LDL-C were significantly decreased and HDL-C was increased in both pioglitazone and dapagliflozin groups（P<0.01）,and the changes in dapagliflozin group were more significant（P<0.05）.In addition,the decrease in TC,TG,LDL-C and the increase in HDL-C in the pioglitazone and dapagliflozin group were more significant than those in the metformin group（P<0.05）.4.Comparison of sex hormone levels among the three groups before and after treatment:after treatment,the levels of T and A in metformin group decreased compared with those before（P<0.05）,while there was no significant difference in DHEA（P>0.05）;After treatment,T,A and DHEA in pioglitazone group and dapagliflozin group were significantly decreased（P<0.01）,but only T level was lower than metformin group（P<0.05）,and other indexes had no significant differences among the three groups（P>0.05）.5.Comparison of insulin resistance indexes among the three groups before and after treatment:after treatment,FINS and HOMA-IR in three groups were significantly decreased,while HOMA-ISI and G₀/I₀were significantly increased（P<0.01）.There was no statistical difference in HOMA-βin metformin group（P>0.05）,and HOMA-βin pioglitazone group and dapagliflozin group was higher than before（P<0.05）,but there was no statistical difference between groups（P>0.05）.After treatment,FINS and HOMA-IR in pioglitazone and dapagliflozin groups were lower than those in metformin group（P<0.05）,and the changes in dapagliflozin group were more significant（P<0.01）.In the combined treatment group HOMA-ISI and G₀/I₀were higher than those in metformin group after treatment,but there was no statistical significance between the two groups（P>0.05）.6.Univariate correlation analysis of insulin resistance index in T2DM patients with PCOS:HOMA-IR was positively correlated with BMI,FBG,2h BG,Hb A1c,T,A and DHEA,and was negatively correlated with HDL-C and dapagliflozin;HOMA-βwas negatively correlated with FBG,2h BG and Hb A1c;FINS were positively correlated with 2h BG,Hb A1c,TC,T,A and DHEA,and was negatively correlated with HDL-C and dapagliflozin;HOMA-ISI was positively correlated with HDL-C and dapagliflozin and negatively correlated with FBG,2h BG,Hb A1c,LDL-C,T,A and DHEA;G₀/I₀was positively correlated with FBG and HDL-C.7.Univariate correlation analysis of sex hormone index in T2DM patients with PCOS:T was positively correlated with 2h BG,FINS and HOMA-IR,and was negatively correlated with HDL-C,HOMA-ISI,G₀/I₀and dapagliflozin;A was positively correlated with 2h BG,Hb A1c,FINS,LDL-C and HOMA-IR,and was negatively correlated with HOMA-ISI and dapagliflozin;DHEA was positively correlated with Hb A1c,FINS and HOMA-IR,and negatively correlated with HDL-C and HOMA-IS.8.Multiple linear regression analysis showed that dapagliflozin was a protective factor for HOMA-IR;2h BG was a risk factor for HOMA-β;pioglitazone and dapagliflozin were protective factors for FINS;2h BG was a risk factor for HOMA-ISI,dapagliflozin was a protective factor for HOMA-ISI;2h BG was a risk factor for G₀/I₀,while pioglitazone and dapagliflozin were protective factors for G₀/I₀.In addition,we found that G₀/I₀was a protective factor for T and LDL-C was a risk factor for A.Conclusions:1.Dapagliflozin combined with metformin in the treatment of T2DM patients with PCOS have better efficacy in terms of weight loss,blood pressure reduction,improvement of glucolipid metabolism and IR than metformin alone.2.Metformin alone,pioglitazone and dapagliflozin combined with metformin can significantly reduce the level of high androgen in T2DM patients with PCOS,and the reduction of testosterone is more significant in the combined treatment group.3.Compared with pioglitazone group,dapagliflozin combined with metformin showed more significant improvement in weight loss,blood pressure reduction,glucolipid metabolism and IR in T2DM patients with PCOS.4.Dapagliflozin is a protective factor for IR in patients with T2DM complicated with PCOS,and no serious adverse reactions occur in the course of medication.Therefore,dapagliflozin is a safe and effective treatment option for patients with T2DM complicated with PCOS.