{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T11:58:29Z","timestamp":1791979109182,"version":"4.4.0"},"reference-count":48,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2020,5,26]],"date-time":"2020-05-26T00:00:00Z","timestamp":1590451200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2016A030313521"],"award-info":[{"award-number":["2016A030313521"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Metabolism Res"],"published-print":{"date-parts":[[2020,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The incidence of type 1 diabetes mellitus (T1DM) is increasing among youth worldwide, translating to an increased risk ofearly\u2010onset cardiovascular disease (CVD). Mounting studies have shown that metformin may reduce maximal carotidintima\u2010media thickness (cIMT), improve insulin resistance and metabolic control in subjects with T1DM, and thus, may extend cardioprotective benefits. This systematic review and meta\u2010analysis was performed to assess the efficacy and safety of metformin added to insulin therapy on reducing CVD risks and improving metabolism in T1DM.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>PubMed, EMBASE, and the Cochrane Library were systematically searched for randomized controlled trials (RCTs) that compared metformin and insulin combination (duration \u22653\u2009months) to insulin treatment alone in T1DM. Data were expressed as weighted\/standardized mean differences (MDs\/SMDs) for continuous outcomes and risk ratios (RRs) for dichotomous outcomes, along with 95% confidence intervals (CIs). The Grading of Recommendations Assessment, Development and Evaluation (GRADE) was used to evaluate the overall certainty of the evidence.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Nineteen RCTs (n = 1540) met the eligibility criteria. Metformin treatment significantly reduced carotid artery intima\u2010media thickness (MD \u22120.06\u2009mm [95% CI \u22120.88, \u22120.28],<jats:italic>P<\/jats:italic>&lt;\u2009.001). Though no significant difference was found in insulin sensitivity (SMD 2.21 [95% CI \u22121.88, 6.29],<jats:italic>P<\/jats:italic>=\u2009.29), the total daily insulin dosage (SMD \u22120.81 [95% CI \u22121.25, \u22120.36],<jats:italic>P<\/jats:italic>&lt;\u2009.001) along with traditional CVD risk factors showed improvement by better glycaemic control, partial lipid profiles, diastolic blood pressure, and limited weight gain, with neutral effect on diabetic ketoacidosis, lactic acidosis, and hypoglycaemia. However, metformin therapy increased the incidence of gastrointestinal adverse events.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Metformin with insulin has the potential to retard the progression of atherosclerosis and provides better metabolic control in patients with T1DM, and thus, providing a potential therapeutic strategy for patients with T1DM on reducing CVD risks.<\/jats:p><\/jats:sec>","DOI":"10.1002\/dmrr.3334","type":"journal-article","created":{"date-parts":[[2020,5,11]],"date-time":"2020-05-11T06:09:48Z","timestamp":1589177388000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Vascular and metabolic effects of metformin added to insulin therapy in patients with type 1 diabetes: A systematic review and<scp>meta\u2010analysis<\/scp>"],"prefix":"10.1002","volume":"36","author":[{"given":"Ying\u2010Shan","family":"Liu","sequence":"first","affiliation":[{"name":"Shenzhen Hospital Southern Medical University Shenzhen China"},{"name":"The Third School of Clinical Medicine Southern Medical University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chu\u2010Na","family":"Chen","sequence":"additional","affiliation":[{"name":"Shenzhen Hospital Southern Medical University Shenzhen China"},{"name":"The Third School of Clinical Medicine Southern Medical University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen\u2010Guo","family":"Chen","sequence":"additional","affiliation":[{"name":"Shenzhen Hospital Southern Medical University Shenzhen China"},{"name":"The Third School of Clinical Medicine Southern Medical University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Peng","sequence":"additional","affiliation":[{"name":"Nanfang Hospital Southern Medical University Guangzhou China"},{"name":"The First School of Clinical Medicine Southern Medical University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao\u2010Pu","family":"Lin","sequence":"additional","affiliation":[{"name":"Nanfang Hospital Southern Medical University Guangzhou China"},{"name":"The First School of Clinical Medicine Southern Medical University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2731-4758","authenticated-orcid":false,"given":"Ling\u2010Ling","family":"Xu","sequence":"additional","affiliation":[{"name":"Shenzhen Hospital Southern Medical University Shenzhen China"},{"name":"The Third School of Clinical Medicine Southern Medical University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,5,26]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1608664"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.2337\/db10-0862"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000000094"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.0000102044.27905.B5"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCIMAGING.112.978114"},{"issue":"7","key":"e_1_2_7_7_1","doi-asserted-by":"crossref","first-page":"461","DOI":"10.20452\/pamw.3533","article-title":"Metformin in type 1 diabetes mellitus? 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