{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T10:44:30Z","timestamp":1792320270763,"version":"4.4.0"},"reference-count":59,"publisher":"The Endocrine Society","issue":"7","license":[{"start":{"date-parts":[[2023,2,17]],"date-time":"2023-02-17T00:00:00Z","timestamp":1676592000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,6,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Context<\/jats:title>\n                  <jats:p>The effect of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on ischemic\/hemorrhagic stroke and transient ischemic attacks (TIA) in type 2 diabetes mellitus (T2DM) remains undetermined.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>To pool effects of GLP-1RAs on adverse cerebrovascular outcomes and investigate impact of baseline variables on these effects.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>PubMed, Embase, Web of Science, Cochrane Library, and clinical trial registry websites were searched for randomized controlled trials (RCTs) \u226524 weeks duration in adults with T2DM (PROSPERO: CRD42022331547). Adjudicated cerebrovascular events in GLP-1RA treatment vs control arms were pooled together to calculate risk ratios (RR) using fixed-effects model. Subgroup analysis was performed based on individual drugs, treatment duration, and baseline patient characteristics. Quality of evidence was assessed using GRADE framework.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We identified 28 RCTs involving 74 148 patients (57% male; median [range], age 58 [52-67] years, BMI 32 [25.4-37.2] kg\/m2, T2DM duration 9 [3.5-15.4] years, treatment duration 52 [24-259] weeks). GLP-1RA use in T2DM was associated with significantly decreased risk of adverse cerebrovascular outcomes vs placebo\/active comparator (RR, 0.83; 95% CI, 0.76-0.91; I2 = 0%). Pooling data from cardiovascular outcome trials (n = 8), GLP-1RA treatment vs placebo was associated with reduced risk of nonfatal stroke (RR, 0.85; 95% CI, 0.76-0.94; I2 = 0%) but not fatal stroke (RR, 0.80; 95% CI, 0.61-1.05; I2 = 0%). GLP-1RA use was associated with reduced risk of ischemic stroke (RCTs = 12; RR, 0.73; 95% CI, 0.60-0.89; I2 = 0%), composite of ischemic stroke\/TIA (RCTs = 16; RR, 0.76; 95% CI, 0.65-0.90; I2 = 0%), but not hemorrhagic stroke (RCTs = 3; RR, 0.92; 95% CI, 0.51-1.64; I2 = 0%). Treatment benefits differed according to baseline eGFR and diabetes duration (P interaction &amp;lt; .1). Benefits were statistically significant for dulaglutide, subcutaneous\/oral semaglutide (P &amp;lt; .05). Sensitivity analysis, excluding shorter-acting lixisenatide, eliminated the heterogeneity between individual GLP-1RA effects.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>GLP-1RAs, particularly longer-acting formulations, reduced ischemic cerebrovascular events in T2DM. Observed benefits were significantly higher in patients with shorter T2DM duration and higher eGFR.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/clinem\/dgad076","type":"journal-article","created":{"date-parts":[[2023,2,17]],"date-time":"2023-02-17T17:29:22Z","timestamp":1676654962000},"page":"1806-1812","source":"Crossref","is-referenced-by-count":41,"title":["GLP-1 Receptor Agonists and Risk of Adverse Cerebrovascular Outcomes in Type 2 Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials"],"prefix":"10.1210","volume":"108","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6656-8569","authenticated-orcid":false,"given":"Mainak","family":"Banerjee","sequence":"first","affiliation":[{"name":"Department of Endocrinology, Institute of Post Graduate Medical Education and Research , Kolkata 700020 , India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rimesh","family":"Pal","sequence":"additional","affiliation":[{"name":"Department 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