This finding also shows that T2DM patients with differences in these factors may react differently to EMPA. A complete of 6 research were contained in the CANA group, with high heterogeneity among the scholarly research. 2 diabetes mellitus. Nevertheless, these outcomes had been heterogeneous extremely, so we executed a subgroup evaluation. The full total outcomes from the subgroup evaluation recommended that by dividing populations into different subgroups, the heterogeneity of every group could possibly be decreased. Conclusions: SGLT inhibitors acquired a good influence on the HbA1c level in sufferers with type 2 diabetes mellitus, but there could be distinctions in the efficiency of SGLT inhibitors in various populations. It really is hoped that even more research will be executed to judge the efficiency and basic safety of SGLT inhibitors in various populations. Registration Amount: CRD42020185025. = 0.05. 3.?Outcomes 3.1. Included sufferers and research Through data source queries, we retrieved a complete of 7657 research. Finally, 27 research[13C39] were included and selected. Zero greyish books was one of them scholarly research. The precise flow diagram is shown in Figure ?Figure1.1. Through data collation for the included studies, a complete of 14,074 patients were enrolled. In each scholarly study, the characteristics of patients in the combined groups were similar. 3.2. Features from the included quality and research evaluation All included research were RCTs. The essential features and quality evaluation from the scholarly research are provided in Desk ?Table11. Desk 1 Simple information and bias risk assessments from the scholarly research. thead Literature quality scoreNo.AuthorYearTrials No First. CountryBackgroundDuration of treatmentGroup-1Group-2Group-3Random series generationAllocation concealmentBlinding of Cyclopamine personnelBlinding and individuals of final result assessmentIncomplete final result dataSelective reportingOther bias /thead 1Bailey, C. J.2010″type”:”clinical-trial”,”attrs”:”text”:”NCT00528879″,”term_id”:”NCT00528879″NCT00528879UKMET24 wkDAPA 5 mgDAPA 10 mgPLAlow risklow risklow risklow risklow risklow risklow risk2Bailey, C. J.2012CUKDiet and Exercise24 wkDAPA 5mgPLAlow risklow risklow risklow risklow risklow riskunclear3Bode, Bruce2013″type”:”clinical-trial”,”attrs”:”text”:”NCT01106651″,”term_id”:”NCT01106651″NCT01106651USUnlimited26 wkCANA 100 mgCANA 300 mgPLAlow risklow risklow risklow risklow risklow riskunclear4Bolinder, J.2014″type”:”clinical-trial”,”attrs”:”text”:”NCT00855166″,”term_id”:”NCT00855166″NCT00855166SwedenMET24 wkDAPA 10 mgPLAlow risklow risklow risklow risklow risklow riskunclear5Dagogo-Jack, S.2018″type”:”clinical-trial”,”attrs”:”text”:”NCT02036515″,”term_id”:”NCT02036515″NCT02036515USMET and SITA24 wkERTU 5 mgERTU 15 mgPLAlow risklow risklow risklow risklow risklow riskunclear6Ferrannini, E.2010″type”:”clinical-trial”,”attrs”:”text”:”NCT00528372″,”term_id”:”NCT00528372″NCT00528372ItalyDiet and Exercise24 wkDAPA 5 mgDAPA 10 mgPLAlow risklow risklow risklow riskunclearlow riskunclear7Forst, T.2014″type”:”clinical-trial”,”attrs”:”text”:”NCT01106690″,”term_id”:”NCT01106690″NCT01106690GermanyMET and pioglitazone26 wk,CANA 100 mgCANA 300 mgPLAlow risklow risklow risklow risklow risklow riskunclear8Haering, Hans-Ulrich2014″type”:”clinical-trial”,”attrs”:”text”:”NCT01159600″,”term_id”:”NCT01159600″NCT01159600GermanyDiet and Exercise24 wkEMPA 10mgEMPA 25 mgPLAlow risklow risklow risklow risklow risklow riskunclear9Jabbour, Serge A.2018″type”:”clinical-trial”,”attrs”:”text”:”NCT00984867″,”term_id”:”NCT00984867″NCT00984867USSITA and/or MET24 wkDAPA 10 mgPLAlow risklow risklow risklow riskunclearlow riskunclear10Ji, L.2019″type”:”clinical-trial”,”attrs”:”text”:”NCT02630706″,”term_id”:”NCT02630706″NCT02630706ChinaMET26 wkERTU 5 mgERTU 15 mgPLAlow risklow risklow risklow risklow risklow riskunclear11Kadowaki, T.2017″type”:”clinical-trial”,”attrs”:”text”:”NCT02354235″,”term_id”:”NCT02354235″NCT02354235JapanTeneligliptin24 wkCANA 100 mgPLAlow risklow risklow risklow risklow risklow riskunclear12Kawamori, R.2018″type”:”clinical-trial”,”attrs”:”text”:”NCT02453555″,”term_id”:”NCT02453555″NCT02453555Japanlinagliptin24 wkDAPA 10 mgPLAlow risklow risklow risklow riskunclearlow riskunclear13Kovacs, C. S.2015″type”:”clinical-trial”,”attrs”:”text”:”NCT01210001″,”term_id”:”NCT01210001″NCT01210001CanadaMET24 wkEMPA 10 mgEMPA 25 mgPLAlow risklow risklow risklow riskunclearlow riskunclear14Mathieu, C.2015″type”:”clinical-trial”,”attrs”:”text”:”NCT01646320″,”term_id”:”NCT01646320″NCT01646320RomaniaMET and Saxagliptin24 wkDAPA 10 mgPLAlow risklow risklow risklow riskunclearlow riskunclear15Matthaei, S.2015″type”:”clinical-trial”,”attrs”:”text”:”NCT01392677″,”term_id”:”NCT01392677″NCT01392677GermanyMET and SUL24 wkDAPA 10 mgPLAlow risklow risklow risklow riskunclearlow riskunclear16Neal, B.2015″type”:”clinical-trial”,”attrs”:”text”:”NCT01032629″,”term_id”:”NCT01032629″NCT01032629AustraliaInsulin24 wkCANA 100 mgCANA 300 mgPLAlow risklow risklow risklow riskunclearlow riskunclear17Romera, I.2016CSpainMET or SUL etc.24 wkEMPA 10 mgEMPA 25 mgPLAlow risklow risklow risklow riskunclearlow riskunclear18Rosenstock, J.2018″type”:”clinical-trial”,”attrs”:”text”:”NCT02033889″,”term_id”:”NCT02033889″NCT02033889USMET26 wkERTU 5 mgERTU 15 mgPLAlow risklow risklow risklow risklow risklow riskunclear19Rosenstock, J.2012″type”:”clinical-trial”,”attrs”:”text”:”NCT00683878″,”term_id”:”NCT00683878″NCT00683878USPioglitazone24 wkDAPA 5 mgDAPA 10 mgPLAlow risklow risklow risklow riskunclearlow riskunclear20Softeland, E.2017″type”:”clinical-trial”,”attrs”:”text”:”NCT01734785″,”term_id”:”NCT01734785″NCT01734785NorwayLinagliptin and MET24 wkEMPA 10 mgEMPA 25 mgPLAlow risklow risklow risklow risklow risklow riskunclear21Stenlof, K.2013″type”:”clinical-trial”,”attrs”:”text”:”NCT01081834″,”term_id”:”NCT01081834″NCT01081834SwedenDiet and Exercise26 wkCANA 100 mgCANA 300 mgPLAlow risklow risklow risklow risklow risklow riskunclear22Strojek, K.2011″type”:”clinical-trial”,”attrs”:”text”:”NCT00680745″,”term_id”:”NCT00680745″NCT00680745PolandGlimepiride24 wkDAPA 5 mgDAPA 10 mgPLAlow risklow risklow risklow risklow risklow riskunclear23Terra, S. G.2017″type”:”clinical-trial”,”attrs”:”text”:”NCT01958671″,”term_id”:”NCT01958671″NCT01958671.Exercise26 and USDiet wkERTU 5 mgERTU 15 mgPLAlow risklow risklow risklow riskunclearlow riskunclear24Wilding, J. P.2013″type”:”clinical-trial”,”attrs”:”text”:”NCT01106625″,”term_id”:”NCT01106625″NCT01106625UKMET and SUL24 wkCANA 100 mgCANA 300 mgPLAlow risklow risklow risklow risklow risklow riskunclear25Yang, W.2016″type”:”clinical-trial”,”attrs”:”text”:”NCT01095666″,”term_id”:”NCT01095666″NCT01095666ChinaMET24 wkDAPA 5 mgDAPA 10 mgPLAlow risklow risklow risklow risklow riskunclearunclear26Yang, W.2018″type”:”clinical-trial”,”attrs”:”text”:”NCT02096705″,”term_id”:”NCT02096705″NCT02096705ChinaInsulin with or without oral antihyperglycemic drugs24 wkDAPA 10 mgPLAlow risklow risklow risklow risklow riskunclearunclear27Roden, M.2013″type”:”clinical-trial”,”attrs”:”text”:”NCT01177813″,”term_id”:”NCT01177813″NCT01177813GermanyDiet and Exercise24 wkEMPA 10 mgEMPA 25 mglow risklow risklow risklow risklow risklow riskunclear Open in another window 3.3. Meta-analysis results 3.3.1. HbA1c Twenty-seven studies reported comparisons from the HbA1c level, including 11 articles on DAPA, 6 articles on EMPA, 4 articles on ERTU, 6 articles on CANA, and 0 articles on SOTA (Fig. ?(Fig.2,2, Table ?Table22). Open in another window Figure 2 Forest plot comparing the SGLT inhibitors versus the placebo on HbA1c. HbA1c = glycated hemoglobin A1c, SGLT = sodium-dependent glucose transporter. Table 2 The meta-analysis results of SGLT inhibitors versus PLA. thead ComparisionSizeTotal em I /em 2Model /thead DAPA 5?mg VS PLA11C0.5[C0.63, C0.38]22%Random effect modelDAPA 10?mg VS PLAC0.61[C0.72, C0.51]60%EMPA 10?mg VS PLA6C0.68[C0.84, C0.51]83%Random effect modelEMPA 25?mg VS PLAC0.67[C0.80, C0.54]68%ERTU 5?mg VS PLA4C0.71[C0.85, C0.56]64%Random effect modelERTU 15?mg VS PLAC0.80[C0.91, C0.70]25%CANA 100?mg VS PLA6C0.71[C0.82, C0.60]44%Random effect modelCANA 300?mg VS PLAC0.88[C1.03, C0.72]70% Open in another window A random-effects model was adopted, as well as the HbA1c level in the DAPA group was less than that in the placebo group: 5?mg DAPA group: em I /em 2?=?22% [MD?=?C0.50, 95% CI (C0.63, C0.38), em P /em ? ?.00001]; 10?mg DAPA group: em I /em 2?=?60% [MD?=?C0.61, 95% CI (C0.72, C0.51), em P /em ? ?.00001]. A random-effects model was adopted, as well as the HbA1c level in the EMPA group was less than that in the placebo group: 10?mg EMPA group: em I /em 2?=?83% [MD?=?C0.68, 95% CI (C0.84, C0.51), em P /em ? ?.0001]; 25?mg.Subgroup analysis according to region could decrease the heterogeneity, with a big change among the subgroups. that by dividing populations into different subgroups, the heterogeneity of every group could possibly be reduced. Conclusions: SGLT inhibitors had an excellent influence on the HbA1c level in patients with type 2 diabetes mellitus, but there could be differences in the efficacy of SGLT inhibitors in various populations. It really is hoped that more studies will end up being conducted to judge the protection and efficiency of SGLT inhibitors in various populations. Registration Number: CRD42020185025. = 0.05. 3.?Results 3.1. Included studies and patients Through database searches, we retrieved a complete of 7657 studies. Finally, 27 studies[13C39] were selected and included. No grey literature was one of them study. The precise flow diagram is shown in Figure ?Figure1.1. Through data collation for the included studies, a complete of 14,074 patients were enrolled. In each study, the characteristics of patients in the groups were similar. 3.2. Characteristics from the included studies and quality assessment All included studies were RCTs. The essential characteristics and quality assessment from the studies are presented in Table ?Table11. Table 1 Basic information and bias risk assessments from the studies. thead Literature quality scoreNo.First authorYearTrials No.CountryBackgroundDuration of treatmentGroup-1Group-2Group-3Random sequence generationAllocation concealmentBlinding of participants and personnelBlinding of outcome assessmentIncomplete outcome dataSelective reportingOther bias /thead 1Bailey, C. J.2010″type”:”clinical-trial”,”attrs”:”text”:”NCT00528879″,”term_id”:”NCT00528879″NCT00528879UKMET24 wkDAPA 5 mgDAPA 10 mgPLAlow risklow risklow risklow risklow risklow risklow risk2Bailey, C. J.2012CUKDiet and Exercise24 wkDAPA 5mgPLAlow risklow risklow risklow risklow risklow riskunclear3Bode, Bruce2013″type”:”clinical-trial”,”attrs”:”text”:”NCT01106651″,”term_id”:”NCT01106651″NCT01106651USUnlimited26 wkCANA 100 mgCANA 300 mgPLAlow risklow risklow risklow risklow risklow riskunclear4Bolinder, J.2014″type”:”clinical-trial”,”attrs”:”text”:”NCT00855166″,”term_id”:”NCT00855166″NCT00855166SwedenMET24 wkDAPA 10 mgPLAlow risklow risklow risklow risklow risklow riskunclear5Dagogo-Jack, S.2018″type”:”clinical-trial”,”attrs”:”text”:”NCT02036515″,”term_id”:”NCT02036515″NCT02036515USMET and SITA24 wkERTU 5 mgERTU 15 mgPLAlow risklow risklow risklow risklow risklow riskunclear6Ferrannini, E.2010″type”:”clinical-trial”,”attrs”:”text”:”NCT00528372″,”term_id”:”NCT00528372″NCT00528372ItalyDiet and Exercise24 wkDAPA 5 mgDAPA 10 mgPLAlow risklow risklow risklow riskunclearlow riskunclear7Forst, T.2014″type”:”clinical-trial”,”attrs”:”text”:”NCT01106690″,”term_id”:”NCT01106690″NCT01106690GermanyMET and pioglitazone26 wk,CANA 100 mgCANA 300 mgPLAlow risklow risklow risklow risklow risklow riskunclear8Haering, Hans-Ulrich2014″type”:”clinical-trial”,”attrs”:”text”:”NCT01159600″,”term_id”:”NCT01159600″NCT01159600GermanyDiet and Exercise24 wkEMPA 10mgEMPA 25 mgPLAlow risklow risklow risklow risklow risklow riskunclear9Jabbour, Serge A.2018″type”:”clinical-trial”,”attrs”:”text”:”NCT00984867″,”term_id”:”NCT00984867″NCT00984867USSITA and/or MET24 wkDAPA 10 mgPLAlow risklow risklow risklow riskunclearlow riskunclear10Ji, L.2019″type”:”clinical-trial”,”attrs”:”text”:”NCT02630706″,”term_id”:”NCT02630706″NCT02630706ChinaMET26 wkERTU 5 mgERTU 15 mgPLAlow risklow risklow risklow risklow risklow riskunclear11Kadowaki, T.2017″type”:”clinical-trial”,”attrs”:”text”:”NCT02354235″,”term_id”:”NCT02354235″NCT02354235JapanTeneligliptin24 wkCANA 100 mgPLAlow risklow risklow risklow risklow risklow riskunclear12Kawamori, R.2018″type”:”clinical-trial”,”attrs”:”text”:”NCT02453555″,”term_id”:”NCT02453555″NCT02453555Japanlinagliptin24 wkDAPA 10 mgPLAlow risklow risklow risklow riskunclearlow riskunclear13Kovacs, C. S.2015″type”:”clinical-trial”,”attrs”:”text”:”NCT01210001″,”term_id”:”NCT01210001″NCT01210001CanadaMET24 wkEMPA 10 mgEMPA 25 mgPLAlow risklow risklow risklow riskunclearlow riskunclear14Mathieu, C.2015″type”:”clinical-trial”,”attrs”:”text”:”NCT01646320″,”term_id”:”NCT01646320″NCT01646320RomaniaMET and Saxagliptin24 wkDAPA 10 mgPLAlow risklow risklow risklow riskunclearlow riskunclear15Matthaei, S.2015″type”:”clinical-trial”,”attrs”:”text”:”NCT01392677″,”term_id”:”NCT01392677″NCT01392677GermanyMET and SUL24 wkDAPA 10 mgPLAlow risklow risklow risklow riskunclearlow riskunclear16Neal, B.2015″type”:”clinical-trial”,”attrs”:”text”:”NCT01032629″,”term_id”:”NCT01032629″NCT01032629AustraliaInsulin24 wkCANA 100 mgCANA 300 mgPLAlow risklow risklow risklow riskunclearlow riskunclear17Romera, I.2016CSpainMET or SUL etc.24 wkEMPA 10 mgEMPA 25 mgPLAlow risklow risklow risklow riskunclearlow riskunclear18Rosenstock, J.2018″type”:”clinical-trial”,”attrs”:”text”:”NCT02033889″,”term_id”:”NCT02033889″NCT02033889USMET26 wkERTU 5 mgERTU 15 mgPLAlow risklow risklow risklow risklow risklow riskunclear19Rosenstock, J.2012″type”:”clinical-trial”,”attrs”:”text”:”NCT00683878″,”term_id”:”NCT00683878″NCT00683878USPioglitazone24 wkDAPA 5 mgDAPA 10 mgPLAlow risklow risklow risklow riskunclearlow riskunclear20Softeland, E.2017″type”:”clinical-trial”,”attrs”:”text”:”NCT01734785″,”term_id”:”NCT01734785″NCT01734785NorwayLinagliptin and MET24 wkEMPA 10 mgEMPA 25 mgPLAlow risklow risklow risklow risklow risklow riskunclear21Stenlof, K.2013″type”:”clinical-trial”,”attrs”:”text”:”NCT01081834″,”term_id”:”NCT01081834″NCT01081834SwedenDiet and Exercise26 wkCANA 100 mgCANA 300 mgPLAlow risklow risklow risklow risklow risklow riskunclear22Strojek, K.2011″type”:”clinical-trial”,”attrs”:”text”:”NCT00680745″,”term_id”:”NCT00680745″NCT00680745PolandGlimepiride24 wkDAPA 5 mgDAPA 10 mgPLAlow risklow risklow risklow risklow risklow riskunclear23Terra, S. G.2017″type”:”clinical-trial”,”attrs”:”text”:”NCT01958671″,”term_id”:”NCT01958671″NCT01958671.USDiet and Exercise26 wkERTU 5 mgERTU 15 mgPLAlow risklow risklow risklow riskunclearlow riskunclear24Wilding, J. P.2013″type”:”clinical-trial”,”attrs”:”text”:”NCT01106625″,”term_id”:”NCT01106625″NCT01106625UKMET and SUL24 wkCANA 100 mgCANA 300 mgPLAlow risklow risklow risklow risklow risklow riskunclear25Yang, W.2016″type”:”clinical-trial”,”attrs”:”text”:”NCT01095666″,”term_id”:”NCT01095666″NCT01095666ChinaMET24 wkDAPA 5 mgDAPA 10 mgPLAlow risklow risklow risklow risklow riskunclearunclear26Yang, W.2018″type”:”clinical-trial”,”attrs”:”text”:”NCT02096705″,”term_id”:”NCT02096705″NCT02096705ChinaInsulin with or without oral antihyperglycemic drugs24 wkDAPA 10 mgPLAlow risklow risklow risklow risklow riskunclearunclear27Roden, M.2013″type”:”clinical-trial”,”attrs”:”text”:”NCT01177813″,”term_id”:”NCT01177813″NCT01177813GermanyDiet and Exercise24 wkEMPA 10 mgEMPA 25 mglow risklow risklow risklow risklow risklow riskunclear Open in another window 3.3. Meta-analysis results 3.3.1. HbA1c Twenty-seven studies reported comparisons from the HbA1c level, including 11 articles on DAPA, 6 articles on EMPA,.However, there is significant heterogeneity for every SGLT inhibitor, so a random-effects were chosen by us model and performed a subgroup analysis to analyze the possible sources of heterogeneity. A complete of 11 research were contained in the DAPA group, with high heterogeneity among the research. in the efficiency of SGLT inhibitors Cyclopamine in different populations. It is hoped that more studies will be conducted to evaluate the efficacy and safety of SGLT inhibitors in different populations. Registration Number: CRD42020185025. = 0.05. 3.?Results 3.1. Included studies and patients Through database searches, we retrieved a total of 7657 studies. Finally, 27 studies[13C39] were selected and included. No grey literature was included in this study. The specific flow diagram is shown in Figure ?Figure1.1. Through data collation for the included studies, a total of 14,074 patients were enrolled. In each study, the characteristics of patients in the groups were similar. 3.2. Characteristics of the included studies and quality assessment All included studies were RCTs. The basic characteristics and quality assessment of the studies are presented in Table ?Table11. Table 1 Basic information and bias risk assessments of the studies. thead Literature quality scoreNo.First authorYearTrials No.CountryBackgroundDuration of treatmentGroup-1Group-2Group-3Random sequence generationAllocation concealmentBlinding of participants and personnelBlinding of outcome assessmentIncomplete outcome dataSelective reportingOther bias /thead 1Bailey, C. J.2010″type”:”clinical-trial”,”attrs”:”text”:”NCT00528879″,”term_id”:”NCT00528879″NCT00528879UKMET24 wkDAPA 5 mgDAPA 10 mgPLAlow risklow risklow risklow risklow risklow risklow risk2Bailey, C. J.2012CUKDiet and Exercise24 wkDAPA 5mgPLAlow risklow risklow risklow risklow risklow riskunclear3Bode, Bruce2013″type”:”clinical-trial”,”attrs”:”text”:”NCT01106651″,”term_id”:”NCT01106651″NCT01106651USUnlimited26 wkCANA 100 mgCANA 300 mgPLAlow risklow risklow risklow risklow risklow riskunclear4Bolinder, J.2014″type”:”clinical-trial”,”attrs”:”text”:”NCT00855166″,”term_id”:”NCT00855166″NCT00855166SwedenMET24 wkDAPA 10 mgPLAlow risklow risklow risklow risklow risklow riskunclear5Dagogo-Jack, S.2018″type”:”clinical-trial”,”attrs”:”text”:”NCT02036515″,”term_id”:”NCT02036515″NCT02036515USMET and SITA24 wkERTU 5 mgERTU 15 mgPLAlow risklow risklow risklow risklow risklow riskunclear6Ferrannini, E.2010″type”:”clinical-trial”,”attrs”:”text”:”NCT00528372″,”term_id”:”NCT00528372″NCT00528372ItalyDiet and Exercise24 wkDAPA 5 mgDAPA 10 mgPLAlow risklow risklow risklow riskunclearlow riskunclear7Forst, T.2014″type”:”clinical-trial”,”attrs”:”text”:”NCT01106690″,”term_id”:”NCT01106690″NCT01106690GermanyMET and pioglitazone26 wk,CANA 100 mgCANA 300 mgPLAlow risklow risklow risklow risklow risklow riskunclear8Haering, Hans-Ulrich2014″type”:”clinical-trial”,”attrs”:”text”:”NCT01159600″,”term_id”:”NCT01159600″NCT01159600GermanyDiet and Exercise24 wkEMPA 10mgEMPA 25 mgPLAlow risklow risklow risklow risklow risklow riskunclear9Jabbour, Serge A.2018″type”:”clinical-trial”,”attrs”:”text”:”NCT00984867″,”term_id”:”NCT00984867″NCT00984867USSITA and/or MET24 wkDAPA 10 mgPLAlow risklow risklow risklow riskunclearlow riskunclear10Ji, L.2019″type”:”clinical-trial”,”attrs”:”text”:”NCT02630706″,”term_id”:”NCT02630706″NCT02630706ChinaMET26 wkERTU 5 mgERTU 15 mgPLAlow risklow risklow risklow risklow risklow riskunclear11Kadowaki, T.2017″type”:”clinical-trial”,”attrs”:”text”:”NCT02354235″,”term_id”:”NCT02354235″NCT02354235JapanTeneligliptin24 wkCANA 100 mgPLAlow risklow risklow risklow risklow risklow riskunclear12Kawamori, R.2018″type”:”clinical-trial”,”attrs”:”text”:”NCT02453555″,”term_id”:”NCT02453555″NCT02453555Japanlinagliptin24 wkDAPA 10 mgPLAlow risklow risklow risklow riskunclearlow riskunclear13Kovacs, C. S.2015″type”:”clinical-trial”,”attrs”:”text”:”NCT01210001″,”term_id”:”NCT01210001″NCT01210001CanadaMET24 wkEMPA 10 mgEMPA 25 mgPLAlow risklow risklow risklow riskunclearlow riskunclear14Mathieu, C.2015″type”:”clinical-trial”,”attrs”:”text”:”NCT01646320″,”term_id”:”NCT01646320″NCT01646320RomaniaMET and Saxagliptin24 wkDAPA 10 mgPLAlow risklow risklow risklow riskunclearlow riskunclear15Matthaei, S.2015″type”:”clinical-trial”,”attrs”:”text”:”NCT01392677″,”term_id”:”NCT01392677″NCT01392677GermanyMET and SUL24 wkDAPA 10 mgPLAlow risklow risklow risklow riskunclearlow riskunclear16Neal, B.2015″type”:”clinical-trial”,”attrs”:”text”:”NCT01032629″,”term_id”:”NCT01032629″NCT01032629AustraliaInsulin24 Cyclopamine wkCANA 100 mgCANA 300 mgPLAlow risklow risklow risklow riskunclearlow riskunclear17Romera, I.2016CSpainMET or SUL and so on.24 wkEMPA 10 mgEMPA 25 mgPLAlow risklow risklow risklow riskunclearlow riskunclear18Rosenstock, J.2018″type”:”clinical-trial”,”attrs”:”text”:”NCT02033889″,”term_id”:”NCT02033889″NCT02033889USMET26 wkERTU 5 mgERTU 15 mgPLAlow risklow risklow risklow risklow risklow riskunclear19Rosenstock, J.2012″type”:”clinical-trial”,”attrs”:”text”:”NCT00683878″,”term_id”:”NCT00683878″NCT00683878USPioglitazone24 wkDAPA 5 mgDAPA 10 mgPLAlow risklow risklow risklow riskunclearlow riskunclear20Softeland, E.2017″type”:”clinical-trial”,”attrs”:”text”:”NCT01734785″,”term_id”:”NCT01734785″NCT01734785NorwayLinagliptin and MET24 wkEMPA 10 mgEMPA 25 mgPLAlow risklow risklow Cyclopamine risklow risklow risklow riskunclear21Stenlof, K.2013″type”:”clinical-trial”,”attrs”:”text”:”NCT01081834″,”term_id”:”NCT01081834″NCT01081834SwedenDiet and Exercise26 wkCANA 100 mgCANA 300 mgPLAlow risklow risklow risklow risklow risklow riskunclear22Strojek, K.2011″type”:”clinical-trial”,”attrs”:”text”:”NCT00680745″,”term_id”:”NCT00680745″NCT00680745PolandGlimepiride24 wkDAPA 5 mgDAPA 10 mgPLAlow risklow risklow risklow risklow risklow riskunclear23Terra, S. G.2017″type”:”clinical-trial”,”attrs”:”text”:”NCT01958671″,”term_id”:”NCT01958671″NCT01958671.USDiet and Exercise26 wkERTU 5 mgERTU 15 mgPLAlow risklow risklow risklow riskunclearlow riskunclear24Wilding, J. P.2013″type”:”clinical-trial”,”attrs”:”text”:”NCT01106625″,”term_id”:”NCT01106625″NCT01106625UKMET and SUL24 wkCANA 100 mgCANA 300 mgPLAlow risklow risklow risklow risklow risklow riskunclear25Yang, W.2016″type”:”clinical-trial”,”attrs”:”text”:”NCT01095666″,”term_id”:”NCT01095666″NCT01095666ChinaMET24 wkDAPA 5 mgDAPA 10 mgPLAlow risklow risklow risklow risklow riskunclearunclear26Yang, W.2018″type”:”clinical-trial”,”attrs”:”text”:”NCT02096705″,”term_id”:”NCT02096705″NCT02096705ChinaInsulin with or without oral antihyperglycemic drugs24 wkDAPA 10 mgPLAlow risklow risklow risklow risklow riskunclearunclear27Roden, M.2013″type”:”clinical-trial”,”attrs”:”text”:”NCT01177813″,”term_id”:”NCT01177813″NCT01177813GermanyDiet and Exercise24 wkEMPA 10 mgEMPA 25 mglow risklow risklow risklow risklow risklow riskunclear Open in a separate window 3.3. Meta-analysis results 3.3.1. HbA1c Twenty-seven studies reported comparisons of the HbA1c level, including 11 articles on DAPA, 6 articles on EMPA, 4 articles on ERTU, 6 articles on CANA, and 0 articles on SOTA (Fig. ?(Fig.2,2, Table ?Table22). Open in.We used two methods to establish subgroup analysis. the heterogeneity of each group could be reduced. Conclusions: SGLT inhibitors had a good effect on the HbA1c level in patients with type 2 diabetes mellitus, but there might be differences in the efficacy of SGLT inhibitors in different populations. It is hoped that more studies will be conducted to evaluate the efficacy and safety of SGLT inhibitors in different populations. Registration Number: CRD42020185025. = 0.05. 3.?Results 3.1. Included studies and patients Through database searches, we retrieved a total of 7657 studies. Finally, 27 studies[13C39] were selected and included. No grey literature was included in this study. The precise flow diagram is shown in Figure ?Figure1.1. Through data collation for the included studies, a complete of 14,074 patients were enrolled. In each study, the characteristics of patients in the groups were similar. 3.2. Characteristics from the included studies and quality assessment All included studies were RCTs. The essential characteristics and quality assessment from the studies are presented in Table ?Table11. Table 1 Basic information and bias risk assessments from the studies. thead Literature quality scoreNo.First authorYearTrials No.CountryBackgroundDuration of treatmentGroup-1Group-2Group-3Random sequence generationAllocation concealmentBlinding of participants and personnelBlinding of outcome assessmentIncomplete outcome dataSelective reportingOther bias /thead 1Bailey, C. J.2010″type”:”clinical-trial”,”attrs”:”text”:”NCT00528879″,”term_id”:”NCT00528879″NCT00528879UKMET24 wkDAPA 5 mgDAPA 10 mgPLAlow risklow risklow risklow risklow risklow risklow risk2Bailey, C. J.2012CUKDiet and Exercise24 wkDAPA 5mgPLAlow risklow risklow risklow risklow risklow riskunclear3Bode, Bruce2013″type”:”clinical-trial”,”attrs”:”text”:”NCT01106651″,”term_id”:”NCT01106651″NCT01106651USUnlimited26 wkCANA 100 mgCANA 300 mgPLAlow risklow risklow risklow risklow risklow riskunclear4Bolinder, J.2014″type”:”clinical-trial”,”attrs”:”text”:”NCT00855166″,”term_id”:”NCT00855166″NCT00855166SwedenMET24 wkDAPA 10 mgPLAlow risklow risklow risklow risklow risklow riskunclear5Dagogo-Jack, S.2018″type”:”clinical-trial”,”attrs”:”text”:”NCT02036515″,”term_id”:”NCT02036515″NCT02036515USMET and SITA24 wkERTU 5 mgERTU 15 mgPLAlow risklow risklow risklow risklow risklow riskunclear6Ferrannini, E.2010″type”:”clinical-trial”,”attrs”:”text”:”NCT00528372″,”term_id”:”NCT00528372″NCT00528372ItalyDiet and Exercise24 wkDAPA 5 mgDAPA 10 mgPLAlow risklow risklow risklow riskunclearlow riskunclear7Forst, T.2014″type”:”clinical-trial”,”attrs”:”text”:”NCT01106690″,”term_id”:”NCT01106690″NCT01106690GermanyMET and pioglitazone26 wk,CANA 100 mgCANA 300 mgPLAlow risklow risklow risklow risklow risklow riskunclear8Haering, Hans-Ulrich2014″type”:”clinical-trial”,”attrs”:”text”:”NCT01159600″,”term_id”:”NCT01159600″NCT01159600GermanyDiet and Exercise24 wkEMPA 10mgEMPA 25 mgPLAlow risklow risklow risklow risklow risklow riskunclear9Jabbour, Serge A.2018″type”:”clinical-trial”,”attrs”:”text”:”NCT00984867″,”term_id”:”NCT00984867″NCT00984867USSITA and/or MET24 wkDAPA 10 mgPLAlow risklow risklow risklow riskunclearlow riskunclear10Ji, L.2019″type”:”clinical-trial”,”attrs”:”text”:”NCT02630706″,”term_id”:”NCT02630706″NCT02630706ChinaMET26 wkERTU 5 mgERTU 15 mgPLAlow risklow risklow risklow risklow risklow riskunclear11Kadowaki, T.2017″type”:”clinical-trial”,”attrs”:”text”:”NCT02354235″,”term_id”:”NCT02354235″NCT02354235JapanTeneligliptin24 wkCANA 100 mgPLAlow risklow risklow risklow risklow risklow riskunclear12Kawamori, R.2018″type”:”clinical-trial”,”attrs”:”text”:”NCT02453555″,”term_id”:”NCT02453555″NCT02453555Japanlinagliptin24 wkDAPA 10 mgPLAlow risklow risklow risklow riskunclearlow riskunclear13Kovacs, C. S.2015″type”:”clinical-trial”,”attrs”:”text”:”NCT01210001″,”term_id”:”NCT01210001″NCT01210001CanadaMET24 wkEMPA 10 mgEMPA 25 mgPLAlow risklow risklow risklow riskunclearlow riskunclear14Mathieu, C.2015″type”:”clinical-trial”,”attrs”:”text”:”NCT01646320″,”term_id”:”NCT01646320″NCT01646320RomaniaMET and Saxagliptin24 wkDAPA 10 mgPLAlow risklow risklow risklow riskunclearlow riskunclear15Matthaei, S.2015″type”:”clinical-trial”,”attrs”:”text”:”NCT01392677″,”term_id”:”NCT01392677″NCT01392677GermanyMET and SUL24 wkDAPA 10 mgPLAlow risklow risklow risklow riskunclearlow riskunclear16Neal, B.2015″type”:”clinical-trial”,”attrs”:”text”:”NCT01032629″,”term_id”:”NCT01032629″NCT01032629AustraliaInsulin24 wkCANA 100 mgCANA 300 mgPLAlow risklow risklow risklow riskunclearlow riskunclear17Romera, I.2016CSpainMET or SUL etc.24 wkEMPA 10 mgEMPA 25 mgPLAlow risklow risklow risklow riskunclearlow riskunclear18Rosenstock, J.2018″type”:”clinical-trial”,”attrs”:”text”:”NCT02033889″,”term_id”:”NCT02033889″NCT02033889USMET26 wkERTU 5 mgERTU 15 mgPLAlow risklow risklow risklow risklow risklow riskunclear19Rosenstock, J.2012″type”:”clinical-trial”,”attrs”:”text”:”NCT00683878″,”term_id”:”NCT00683878″NCT00683878USPioglitazone24 wkDAPA 5 mgDAPA 10 mgPLAlow risklow risklow risklow riskunclearlow riskunclear20Softeland, E.2017″type”:”clinical-trial”,”attrs”:”text”:”NCT01734785″,”term_id”:”NCT01734785″NCT01734785NorwayLinagliptin and MET24 wkEMPA 10 mgEMPA 25 mgPLAlow risklow risklow risklow risklow risklow riskunclear21Stenlof, K.2013″type”:”clinical-trial”,”attrs”:”text”:”NCT01081834″,”term_id”:”NCT01081834″NCT01081834SwedenDiet and Exercise26 wkCANA 100 mgCANA 300 mgPLAlow risklow risklow risklow risklow risklow riskunclear22Strojek, K.2011″type”:”clinical-trial”,”attrs”:”text”:”NCT00680745″,”term_id”:”NCT00680745″NCT00680745PolandGlimepiride24 wkDAPA 5 mgDAPA 10 mgPLAlow risklow risklow risklow risklow risklow riskunclear23Terra, S. G.2017″type”:”clinical-trial”,”attrs”:”text”:”NCT01958671″,”term_id”:”NCT01958671″NCT01958671.USDiet and Exercise26 wkERTU 5 mgERTU 15 mgPLAlow risklow risklow risklow riskunclearlow riskunclear24Wilding, J. P.2013″type”:”clinical-trial”,”attrs”:”text”:”NCT01106625″,”term_id”:”NCT01106625″NCT01106625UKMET and SUL24 wkCANA 100 mgCANA 300 mgPLAlow risklow risklow risklow risklow risklow riskunclear25Yang, W.2016″type”:”clinical-trial”,”attrs”:”text”:”NCT01095666″,”term_id”:”NCT01095666″NCT01095666ChinaMET24 wkDAPA 5 mgDAPA 10 mgPLAlow risklow risklow risklow risklow riskunclearunclear26Yang, W.2018″type”:”clinical-trial”,”attrs”:”text”:”NCT02096705″,”term_id”:”NCT02096705″NCT02096705ChinaInsulin with or without oral antihyperglycemic drugs24 wkDAPA 10 mgPLAlow risklow risklow risklow risklow riskunclearunclear27Roden, M.2013″type”:”clinical-trial”,”attrs”:”text”:”NCT01177813″,”term_id”:”NCT01177813″NCT01177813GermanyDiet and Exercise24 wkEMPA 10 mgEMPA 25 mglow risklow risklow risklow risklow risklow riskunclear Open in another window 3.3. Meta-analysis results 3.3.1. HbA1c Twenty-seven studies reported comparisons from the HbA1c level, including 11 articles on DAPA, 6 articles on EMPA, 4 articles on ERTU, 6 articles on CANA, and 0 articles on SOTA (Fig. ?(Fig.2,2, Table ?Table22). Open in another window Figure 2 Forest plot comparing the SGLT inhibitors versus the placebo on HbA1c. HbA1c = glycated hemoglobin A1c, SGLT = sodium-dependent glucose transporter. Table 2 The meta-analysis results of SGLT inhibitors versus PLA. thead ComparisionSizeTotal em I /em 2Model /thead DAPA 5?mg VS PLA11C0.5[C0.63, C0.38]22%Random effect modelDAPA 10?mg VS PLAC0.61[C0.72, C0.51]60%EMPA 10?mg VS PLA6C0.68[C0.84, C0.51]83%Random effect modelEMPA 25?mg VS PLAC0.67[C0.80, C0.54]68%ERTU 5?mg VS PLA4C0.71[C0.85, C0.56]64%Random effect modelERTU 15?mg VS PLAC0.80[C0.91, C0.70]25%CANA 100?mg VS PLA6C0.71[C0.82, C0.60]44%Random effect modelCANA 300?mg VS PLAC0.88[C1.03, C0.72]70% Open in another window A random-effects model was adopted, and the HbA1c level in the DAPA group was less than that in the placebo group: 5?mg DAPA group: em I /em 2?=?22% [MD?=?C0.50, 95% CI (C0.63, C0.38), em P /em ? ?.00001]; 10?mg DAPA group: em I /em 2?=?60% [MD?=?C0.61, 95% CI (C0.72, C0.51), em P /em ? ?.00001]. A random-effects model was adopted, and the HbA1c level in the EMPA group was less than that in the placebo group: 10?mg EMPA group: em I /em 2?=?83%.The total results of each study were all positive; that’s, SGLT inhibitors were effective for patients with T2DM, independent of region. be conducted to judge the efficacy and safety of SGLT inhibitors in various populations. Registration Number: CRD42020185025. = 0.05. 3.?Results 3.1. Included studies and patients Through database searches, we retrieved a complete of 7657 studies. Finally, 27 studies[13C39] were selected and included. No grey literature was one of them study. The precise flow diagram is shown in Figure ?Figure1.1. Through data collation for the included studies, a complete of 14,074 patients were enrolled. In each study, the characteristics of patients in the groups were similar. 3.2. Characteristics of the included studies and quality assessment All included studies were RCTs. The essential characteristics and quality assessment of the studies are presented in Table ?Table11. Table 1 Basic information and bias risk assessments of the studies. thead Literature quality scoreNo.First authorYearTrials No.CountryBackgroundDuration of treatmentGroup-1Group-2Group-3Random sequence generationAllocation concealmentBlinding of participants and personnelBlinding of outcome assessmentIncomplete outcome dataSelective reportingOther bias /thead 1Bailey, C. J.2010″type”:”clinical-trial”,”attrs”:”text”:”NCT00528879″,”term_id”:”NCT00528879″NCT00528879UKMET24 wkDAPA 5 mgDAPA 10 mgPLAlow risklow risklow risklow risklow risklow risklow risk2Bailey, C. J.2012CUKDiet and Exercise24 wkDAPA 5mgPLAlow risklow risklow risklow risklow risklow riskunclear3Bode, Bruce2013″type”:”clinical-trial”,”attrs”:”text”:”NCT01106651″,”term_id”:”NCT01106651″NCT01106651USUnlimited26 wkCANA 100 mgCANA 300 mgPLAlow risklow risklow risklow risklow risklow riskunclear4Bolinder, J.2014″type”:”clinical-trial”,”attrs”:”text”:”NCT00855166″,”term_id”:”NCT00855166″NCT00855166SwedenMET24 wkDAPA 10 mgPLAlow risklow risklow risklow risklow risklow riskunclear5Dagogo-Jack, S.2018″type”:”clinical-trial”,”attrs”:”text”:”NCT02036515″,”term_id”:”NCT02036515″NCT02036515USMET and SITA24 wkERTU 5 mgERTU 15 mgPLAlow risklow risklow risklow risklow risklow riskunclear6Ferrannini, E.2010″type”:”clinical-trial”,”attrs”:”text”:”NCT00528372″,”term_id”:”NCT00528372″NCT00528372ItalyDiet and Exercise24 wkDAPA 5 mgDAPA 10 mgPLAlow risklow risklow risklow riskunclearlow riskunclear7Forst, T.2014″type”:”clinical-trial”,”attrs”:”text”:”NCT01106690″,”term_id”:”NCT01106690″NCT01106690GermanyMET and pioglitazone26 wk,CANA 100 mgCANA 300 mgPLAlow risklow risklow risklow risklow risklow Mouse monoclonal to SIRT1 riskunclear8Haering, Hans-Ulrich2014″type”:”clinical-trial”,”attrs”:”text”:”NCT01159600″,”term_id”:”NCT01159600″NCT01159600GermanyDiet and Exercise24 wkEMPA 10mgEMPA 25 mgPLAlow risklow risklow risklow risklow risklow riskunclear9Jabbour, Serge A.2018″type”:”clinical-trial”,”attrs”:”text”:”NCT00984867″,”term_id”:”NCT00984867″NCT00984867USSITA and/or MET24 wkDAPA 10 mgPLAlow risklow risklow risklow riskunclearlow riskunclear10Ji, L.2019″type”:”clinical-trial”,”attrs”:”text”:”NCT02630706″,”term_id”:”NCT02630706″NCT02630706ChinaMET26 wkERTU 5 mgERTU 15 mgPLAlow risklow risklow risklow risklow risklow riskunclear11Kadowaki, T.2017″type”:”clinical-trial”,”attrs”:”text”:”NCT02354235″,”term_id”:”NCT02354235″NCT02354235JapanTeneligliptin24 wkCANA 100 mgPLAlow risklow risklow risklow risklow risklow riskunclear12Kawamori, R.2018″type”:”clinical-trial”,”attrs”:”text”:”NCT02453555″,”term_id”:”NCT02453555″NCT02453555Japanlinagliptin24 wkDAPA 10 mgPLAlow risklow risklow risklow riskunclearlow riskunclear13Kovacs, C. S.2015″type”:”clinical-trial”,”attrs”:”text”:”NCT01210001″,”term_id”:”NCT01210001″NCT01210001CanadaMET24 wkEMPA 10 mgEMPA 25 mgPLAlow risklow risklow risklow riskunclearlow riskunclear14Mathieu, C.2015″type”:”clinical-trial”,”attrs”:”text”:”NCT01646320″,”term_id”:”NCT01646320″NCT01646320RomaniaMET and Saxagliptin24 wkDAPA 10 mgPLAlow risklow risklow risklow riskunclearlow riskunclear15Matthaei, S.2015″type”:”clinical-trial”,”attrs”:”text”:”NCT01392677″,”term_id”:”NCT01392677″NCT01392677GermanyMET and SUL24 wkDAPA 10 mgPLAlow risklow risklow risklow riskunclearlow riskunclear16Neal, B.2015″type”:”clinical-trial”,”attrs”:”text”:”NCT01032629″,”term_id”:”NCT01032629″NCT01032629AustraliaInsulin24 wkCANA 100 mgCANA 300 mgPLAlow risklow risklow risklow riskunclearlow riskunclear17Romera, I.2016CSpainMET or SUL etc.24 wkEMPA 10 mgEMPA 25 mgPLAlow risklow risklow risklow riskunclearlow riskunclear18Rosenstock, J.2018″type”:”clinical-trial”,”attrs”:”text”:”NCT02033889″,”term_id”:”NCT02033889″NCT02033889USMET26 wkERTU 5 mgERTU 15 mgPLAlow risklow risklow risklow risklow risklow riskunclear19Rosenstock, J.2012″type”:”clinical-trial”,”attrs”:”text”:”NCT00683878″,”term_id”:”NCT00683878″NCT00683878USPioglitazone24 wkDAPA 5 mgDAPA 10 mgPLAlow risklow risklow risklow riskunclearlow riskunclear20Softeland, E.2017″type”:”clinical-trial”,”attrs”:”text”:”NCT01734785″,”term_id”:”NCT01734785″NCT01734785NorwayLinagliptin and MET24 wkEMPA 10 mgEMPA 25 mgPLAlow risklow risklow risklow risklow risklow riskunclear21Stenlof, K.2013″type”:”clinical-trial”,”attrs”:”text”:”NCT01081834″,”term_id”:”NCT01081834″NCT01081834SwedenDiet and Exercise26 wkCANA 100 mgCANA 300 mgPLAlow risklow risklow risklow risklow risklow riskunclear22Strojek, K.2011″type”:”clinical-trial”,”attrs”:”text”:”NCT00680745″,”term_id”:”NCT00680745″NCT00680745PolandGlimepiride24 wkDAPA 5 mgDAPA 10 mgPLAlow risklow risklow risklow risklow risklow riskunclear23Terra, S. G.2017″type”:”clinical-trial”,”attrs”:”text”:”NCT01958671″,”term_id”:”NCT01958671″NCT01958671.USDiet and Exercise26 wkERTU 5 mgERTU 15 mgPLAlow risklow risklow risklow riskunclearlow riskunclear24Wilding, J. P.2013″type”:”clinical-trial”,”attrs”:”text”:”NCT01106625″,”term_id”:”NCT01106625″NCT01106625UKMET and SUL24 wkCANA 100 mgCANA 300 mgPLAlow risklow risklow risklow risklow risklow riskunclear25Yang, W.2016″type”:”clinical-trial”,”attrs”:”text”:”NCT01095666″,”term_id”:”NCT01095666″NCT01095666ChinaMET24 wkDAPA 5 mgDAPA 10 mgPLAlow risklow risklow risklow risklow riskunclearunclear26Yang, W.2018″type”:”clinical-trial”,”attrs”:”text”:”NCT02096705″,”term_id”:”NCT02096705″NCT02096705ChinaInsulin with or without oral antihyperglycemic drugs24 wkDAPA 10 mgPLAlow risklow risklow risklow risklow riskunclearunclear27Roden, M.2013″type”:”clinical-trial”,”attrs”:”text”:”NCT01177813″,”term_id”:”NCT01177813″NCT01177813GermanyDiet and Exercise24 wkEMPA 10 mgEMPA 25 mglow risklow risklow risklow risklow risklow riskunclear Open in a separate window 3.3. Meta-analysis results 3.3.1. HbA1c Twenty-seven studies reported comparisons of the HbA1c level, including 11 articles on DAPA, 6 articles on EMPA, 4 articles on ERTU, 6 articles on CANA, and 0 articles on SOTA (Fig. ?(Fig.2,2, Table ?Table22). Open in a separate window Figure 2 Forest plot comparing the SGLT inhibitors versus the placebo on HbA1c. HbA1c = glycated hemoglobin A1c, SGLT = sodium-dependent glucose transporter. Table 2 The meta-analysis results of SGLT inhibitors versus PLA. thead ComparisionSizeTotal em I /em 2Model /thead DAPA 5?mg VS PLA11C0.5[C0.63, C0.38]22%Random effect modelDAPA 10?mg.