{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T20:37:20Z","timestamp":1793824640117,"version":"4.6.1"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T00:00:00Z","timestamp":1765324800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study assesses the efficacy and safety of the novel oral small molecule glucagon-like peptide-1 receptor agonists (GLP-1 RAs) danuglipron and orforglipron in the treatment of type 2 diabetes (T2DM) and obesity through systematic review and meta-analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Electronic databases (PubMed, Web of Science, Cochrane Library and Embase) were systematically searched up to 20 May 2025 to include randomised controlled trials evaluating danuglipron\/orforglipron in patients with T2DM and\/or obesity. Changes in glycated haemoglobin (HbA1c), fasting plasma glucose (FPG), fasting plasma insulin (FPI), weight and body mass index (BMI) compared with baseline post-treatment were evaluated using random-\/fixed-effects models, alongside safety outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Eight studies with low bias risk involving 1,454 participants were analysed. Meta-analysis results demonstrated that danuglipron significantly decreased HbA1c (mean difference [MD]: \u22120.90; 95% CI: \u22121.06, \u22120.74), FPG (MD: \u221224.66; 95% CI: \u221230.45, \u221218.86) and weight (MD: \u22122.17; 95% CI: \u22123.10,\u00a0\u22121.23) and improved FPI (MD: 2.94; 95% CI: 1.50, 4.38). Orforglipron also showed significant positive effects on HbA1c (MD: \u22121.02; 95% CI: \u22121.18,\u00a0\u22120.86), FPG (MD: \u221226.91; 95% CI: \u221231.05, \u221222.78), weight (MD: \u22126.28; 95% CI: \u22128.45, \u22124.11) and BMI (MD: \u22122.64; 95% CI: \u22123.38, \u22121.89). However, both danuglipron and orforglipron were associated with the occurrence of treatment-related adverse events and gastrointestinal adverse events (AEs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The oral GLP-1 RAs danuglipron and orforglipron are capable of improving blood glucose levels and reducing weight; however, they also pose an increased risk of gastrointestinal AEs. Further longitudinal studies are warranted to gain a deeper understanding of their efficacy, safety and tolerability.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2025.1646956","type":"journal-article","created":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T05:26:17Z","timestamp":1765344377000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["The efficacy and safety of danuglipron and orforglipron in patients with type 2 diabetes and obesity: a systematic review and 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