{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T10:13:12Z","timestamp":1784887992563,"version":"3.55.0"},"reference-count":35,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2019,1,31]],"date-time":"2019-01-31T00:00:00Z","timestamp":1548892800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Diabetes"],"published-print":{"date-parts":[[2019,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The safety and efficacy of sodium glucose co\u2010transporter 2 (SGLT2) inhibitors in a dose\u2010dependent manner for type 1 diabetes mellitus (T1DM) are unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Randomized clinical trials (RCT) were searched from PubMed, EMBASE, the Cochrane Library, Web of Science and ClinicalTrials until August 2018.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Thirteen RCT with 5397 participants were included. SGLT2 inhibitors were proved to be effective in glycemic control and weight loss in T1DM. In the subgroups of different doses, SGLT2 inhibitors exhibited reductions in glycated haemoglobin, bodyweight, fasting plasma glucose, mean daily glucose, basal insulin dose, bolus insulin dose, estimated glomerular filtration rate and systolic blood pressure, and elevations in the mean amplitude of glucose excursions, and percentage of time in target glucose range in a dose\u2010dependent manner. Reductions in total insulin dose and urinary glucose excretion were dose\u2010independent. SGLT2 inhibitors did not induce hypoglycemia, severe hypoglycemia, cardiovascular events, bone fracture and all\u2010cause mortality, but increased the risk of adverse events (AE), adverse events related to the drug treatment, infections, diabetic ketoacidosis (DKA) and renal disease correlated with dosage.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>SGLT2 inhibitors in high and moderate doses can achieve a better outcome on efficacy, but may induce a higher risk of adverse events, especially DKA.<\/jats:p><\/jats:sec>","DOI":"10.1111\/1753-0407.12890","type":"journal-article","created":{"date-parts":[[2018,12,19]],"date-time":"2018-12-19T06:39:44Z","timestamp":1545201584000},"page":"645-655","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Safety and efficacy of sodium glucose co\u2010transporter 2 inhibitors combined with insulin in adults with type 1 diabetes: A meta\u2010analysis of randomized controlled trials"],"prefix":"10.1111","volume":"11","author":[{"given":"Kexin","family":"Li","sequence":"first","affiliation":[{"name":"Department of Nephrology The Second Affiliated Hospital of Nanchang University  Jiangxi China"},{"name":"Grade 2015 Joint Programme of Nanchang University and Queen Mary University of London, Nanchang University  Jiangxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaosi","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Nephrology The Second Affiliated Hospital of Nanchang University  Jiangxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,1,31]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2017.139"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(16)00039-5"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMe1711296"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-018-4671-6"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2018.01.004"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.13260"},{"key":"e_1_2_6_8_1","article-title":"The efficacy and safety of SGLT2 inhibitors for adjunctive treatment of type 1 diabetes: a systematic review and meta\u2010analysis","volume":"7","author":"Chen J","year":"2017","journal-title":"Sci Rep"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000006944"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.24920\/J1001-9242.2007.003"},{"key":"e_1_2_6_11_1","volume-title":"Cochrane Handbook for Systemic Reviews of Interventions Version 5.1.0","author":"Higgins JPT","year":"2011"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.327.7414.557"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.2307\/2533446"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.315.7109.629"},{"key":"e_1_2_6_15_1","first-page":"529","article-title":"Inclusion of zero total event trials in meta\u2010analysis maintains analytic consistency and incorporates all available data","volume":"7","author":"Firedrich JO","year":"2007","journal-title":"BMC Med Res Methodol."},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc15-1730"},{"key":"e_1_2_6_17_1","first-page":"A76","article-title":"Canagliflozin (CANA) improves glycemic control and reduces glycemic variability in patients with type 1 diabetes mellitus (T1DM) inadequately controlled with insulin","volume":"65","author":"Rodbard HW","year":"2016","journal-title":"Diabetes"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc13-2955"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2016-1451"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(17)30308-X"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc18-0623"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.12494"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1089\/dia.2016.0261"},{"key":"e_1_2_6_24_1","first-page":"A321","article-title":"Empagliflozin (EMPA) decreases glucose exposure and variability in patients with type 1 diabetes (T1DM): continuous glucose monitoring (CGM) data (EASE\u20101)","volume":"64","author":"Famulla S","year":"2015","journal-title":"Diabetes"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.13351"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc14-2806"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1708337"},{"key":"e_1_2_6_28_1","first-page":"87","article-title":"12\u2010week dose\u2010ranging study of sotagliflozin, a dual SGLT1 and SGLT2 inhibitor, as adjunct therapy to insulin in type 1 diabetes, (inTandem4; NCT02459899)","volume":"18","author":"Baker C","year":"2017","journal-title":"Pediatr Diabetes"},{"key":"e_1_2_6_29_1","first-page":"25","article-title":"Efficacy and safety of sotagliflozin, a dual SGLT1 and SGLT2 inhibitor, as adjunct to insulin in young adults with poorly controlled type 1 diabetes (JDRF Study; NCT02383940)","volume":"18","author":"Bode B","year":"2017","journal-title":"Pediatr Diabetes"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc18-0343"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc18-0342"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.28.5.1245"},{"key":"e_1_2_6_33_1","unstructured":"NCT. Empagliflozin and ACEi effects on hyperfiltration in Type 1 diabetes (BETWEEN study).https:\/\/clinicaltrials.gov\/show\/nct02632747.2015. Accessed October 15 2018."},{"key":"e_1_2_6_34_1","unstructured":"NCT. The PK and PD of dapagliflozin therapy in combination with insulin in Japanese subjects with T1DM.https:\/\/clinicaltrials.gov\/show\/nct02582840.2015. Accessed October 15 2018."},{"key":"e_1_2_6_35_1","unstructured":"NCT. Effect of canagliflozin in T1DM (Type 1 diabetes melitus) after interruption of continuous subcutaneous insulin infusion.https:\/\/clinicaltrials.gov\/show\/nct02673138.2016. Accessed October 15 2018."},{"key":"e_1_2_6_36_1","unstructured":"NCT. An investigation into the effect of dapagliflozin on ketogenesis in type 1 diabetes.https:\/\/clinicaltrials.gov\/show\/nct02962492.2016. 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