| Objectives:Polycystic ovary syndrome(PCOS)is a common reproductive endocrine disease associated with obesity and insulin resistance.Canagliflozin(CANA),a kind of sodium-glucose cotransporter-2(SGLT-2)inhibition,which can effectively reduce fat mass,improve glucose homeostasis,relieve oxidative damage and inflammation,a study in which the role of CANA monotherapy in PCOS has been investigated,and it could become a novel option in the PCOS treatment.Nevertheless,trials focused on SGLT-2 combination therapy’s efficacy,and safety in PCOS patients is limited.Hence,the randomized controlled trial compared the efficacy and safety of CANA and metformin(MET)combination therapy and MET monotherapy in endocrine and metabolic profiles of overweight and obese women with PCOS.Methods:Sixty-six patients in this open-label randomized controlled trial were selected from the outpatient clinics of Shengjing Hospital of China Medical University Endocrinology Department,Shenyang,Liaoning,China,from April 2021 to March 2022.Patients were randomly allocated to receive either CANA/MET or MET treatment.The CANA/MET group received CANA 100 mg once daily plus MET 1000 mg twice daily,while the MET group received MET 1000 mg twice daily for three months.All eligible patients were instructed to maintain their habitual diet,exercise level,and contraceptive use throughout the study period.All subjects returned to the hospital at baseline and after 12 weeks of treatment to assess their menstrual cycle,and undergo standard anthropometric measurements:height,weight,body mass index(BMI),blood drawn on an empty stomach for measuring follicle-stimulating hormone(FSH),luteinizing hormone(LH),total testosterone(TT),free androgen index(FAI),and sex hormone binding globulin(SHBG),triglycerides(TG),cholesterol(TC),low-density lipoprotein(LDL-C),apolipoprotein A1(ApoAl),and apolipoprotein B(Apo B).Besides,after baseline and 12-weeks randomization,glucose tolerance and insulin sensitivity were assessed at baseline and 12 weeks post-randomization using the oral glucose tolerance test(OGTT).Blood samples were taken at 0,60,and 120 min after a sugar meal and the area under the glucose curve(AUCGlu)and insulin(AUCIns)were obtained by calculating the sum of the trapezoidal areas between 0,60,and 120 min.We frequently contacted PCOS patients through weekly phone calls,asking about their medication adverse events(AEs).Paired t-test(normal distribution)or Wilcoxon signed-rank test(non-normal distribution)was used for intragroup comparisons for continuous data.In contrast,an independent sample t-test(normal distribution)or Mann-Whitney U test(non-normal distribution)was performed for intergroup comparisons.For categorical variables,the chi-square test was used.Results were obtained using GraphPad Prism(Version 7.0)and SPSS(Version 23.0).Results:After 12 weeks of randomization,within-group comparisons showed a significant decrease in the primary outcome-body weight,but no significant differences were found between the two groups[CANA/MET:-6.66±4.24 vs.MET:-5.85±3.32;(P=0.5386)].In addition,after 12 weeks of treatment,an improvement in menstrual cycle irregularity was detected in CANA/MET group(80.95%,17/21)and MET(80.00%;16/20).There was no significant difference between the two interventions(P=0.6228).There was a clinically significant decrease in TT from baseline both in two groups.Compared to the MET group,the TT in the CANA/MET group showed a more pronounced drop[CANA/MET:-2.49±1.55 vs.MET:-2.20±1.30;(P=0.0223)].No differences were noted in FSH,LH,FAI,and SHBG between the two groups.For glucose homeostasis-related parameters,participants in the CANA/MET group had a significant decrease in AUCGlu[CANA/MET:-158±225.4 vs.MET:2.63±180.7;(P=0.0182)]and the AUCIns/AUCGlu ratio[CANA/MET:-2.86±5.71 vs.MET:0.51±0.61;(P=0.0164)]compared with MET.Decreased AUCGlu and the AUCIns/AUCGlu ratio were observed in the CANA/MET group.However,these differences were not observed in the MET group.There were no significant differences in BMI,FBG,FINS,AUCIns,TG,TC,LDL-C,Apo A1,Apo B,and Apo B/A1 ratio between the two interventions(P>0.05).AEs were seen in 57.70%(15/26)and 68.00%(17/25)of patients in the CANA/MET and MET groups,respectively.Conclusions:In overweight and obese women with PCOS,CANA and MET combination therapy may be similar to MET monotherapy in improving menstrual frequency,weight control,and relieving insulin resistance.CANA/MET may have more benefits in ameliorating hyperandrogenism and glucose homeostasis than MET monotherapy. |
