{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T04:56:22Z","timestamp":1793336182204,"version":"4.5.0"},"reference-count":74,"publisher":"American Medical Association (AMA)","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Intern Med"],"published-print":{"date-parts":[[2026,5,1]]},"abstract":"<jats:sec id=\"ab-ioi250101-4\">\n                    <jats:title>Importance<\/jats:title>\n                    <jats:p>\n                      Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are a novel class of therapeutics approved to treat chronic conditions such as cardiovascular disease, diabetes, and\/or obesity. However, whether GLP-1 RAs\u2019 efficacy varies by age, sex, race and ethnicity, baseline body mass index (BMI), and baseline hemoglobin A\n                      <jats:sub>1c<\/jats:sub>\n                      (HbA\n                      <jats:sub>1c<\/jats:sub>\n                      ) is unclear.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-ioi250101-5\">\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To quantify the heterogeneity of treatment effects (HTE) of GLP-1 RAs, including semaglutide, liraglutide, exenatide, lixisenatide, and dulaglutide, by patient characteristics.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-ioi250101-6\">\n                    <jats:title>Data Sources<\/jats:title>\n                    <jats:p>MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials, from inception through July 26, 2024.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-ioi250101-7\">\n                    <jats:title>Study Selection<\/jats:title>\n                    <jats:p>Pairs of investigators independently screened titles and abstracts and then reviewed eligible full-text articles reporting on randomized clinical trials (RCTs) that compared GLP-1 RAs to placebo or other medications.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-ioi250101-8\">\n                    <jats:title>Data Extraction and Synthesis<\/jats:title>\n                    <jats:p>\n                      Study design, interventions, and comparators, and patient baseline weight and weight change over time (overall and by age, sex, race and ethnicity, BMI, and HbA\n                      <jats:sub>1c<\/jats:sub>\n                      level) were extracted from the data. Risk of bias was assessed using the Cochrane risk of bias tool and meta-analyses were conducted using random-effects models. For each subgroup, RCTs were meta-analyzed where quantitative synthesis was possible, while additional relevant studies were narratively incorporated in the analysis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-ioi250101-9\">\n                    <jats:title>Main Outcomes and Measures<\/jats:title>\n                    <jats:p>\n                      Change in body weight measured in kg (by age, baseline BMI, baseline HbA\n                      <jats:sub>1c<\/jats:sub>\n                      ) or percentage change from baseline (by sex, race and ethnicity).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-ioi250101-10\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Of 7705 unique records, 41 articles representing 64 RCTs were included in the meta-analysis. Of these, 48 RCTs could be individually characterized: they had a mean (SD) study population of 1181 (2513) participants; 51 trials were parallel (98.1%); 51 multicenter (98.1%); and 21 evaluated semaglutide (43.8%) and 9, dulaglutide (18.8%). HTE was most commonly evaluated using baseline BMI (36 RCTs [75.0%]), HbA\n                      <jats:sub>1c<\/jats:sub>\n                      (24 [50.0%]), and age (21 [43.8%]), and less commonly, ethnicity (12 [25.0%]), race (11 [22.9%]), and sex (10 [20.8%]). Among 6 trials (19\u202f906 patients) analyzed by sex, weight loss was greater among women (10.9%; 95% CI, 7.0%-14.8%) than men (6.8%; 95% CI, 4.6%-9.0%). We found no significant HTE by age (7 trials with 4314 patients), race (9 trials, 25\u202f229 patients), ethnicity (7 trials, 8328 patients), baseline BMI (15 trials, 9473 patients across 3 analyses), or baseline HbA\n                      <jats:sub>1c<\/jats:sub>\n                      (4 trials, 1886 patients).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-ioi250101-11\">\n                    <jats:title>Conclusions and Relevance<\/jats:title>\n                    <jats:p>In this systematic review and meta-analysis, GLP-1 RAs produced greater weight loss among women than men; however, their efficacy was consistent across other important subpopulations. These findings may inform clinical decision-making.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1001\/jamainternmed.2025.8222","type":"journal-article","created":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T16:00:39Z","timestamp":1772467239000},"page":"567","source":"Crossref","is-referenced-by-count":26,"title":["Heterogeneity of Treatment Effects of Glucagon-Like Peptide-1 Receptor Agonists for Weight Loss in Adults"],"prefix":"10.1001","volume":"186","author":[{"given":"G. Caleb","family":"Alexander","sequence":"first","affiliation":[{"name":"Center for Drug Safety and Effectiveness, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland"},{"name":"Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland"},{"name":"Division of General Internal Medicine, Johns Hopkins Medicine, Baltimore, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuya","family":"Xiao","sequence":"additional","affiliation":[{"name":"Center for Drug Safety and Effectiveness, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland"},{"name":"Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Dilek","sequence":"additional","affiliation":[{"name":"Center for Drug Safety and Effectiveness, Johns Hopkins Bloomberg School of Public Health, Baltimore, 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