From Glycemic Control to Obesity Management: A 20-year Systematic Evidence Map of GLP-1 Trials and Their Relevance to Metabolic and Bariatric Surgery

Abstract Glucagon-like peptide-1 (GLP-1)-based therapeutics have evolved from glucose-lowering agents into a major component of obesity care, with increasing relevance to metabolic and bariatric surgery (MBS). However, the long-term evolution of the randomized trial ecosystem across the full incretin-agonist spectrum has not been systematically mapped. We conducted a PRISMA 2020-compliant systematic review, evidence map, and bibliometric analysis of randomized controlled trials evaluating GLP-1-based therapeutics, including selective GLP-1 receptor agonists and GLP-1-based co-/tri-agonists. ClinicalTrials.gov, PubMed/MEDLINE, and Scopus were searched for trials registered and/or published between July 1, 2005, and June 30, 2025. After deduplication and eligibility assessment, 517 unique randomized trials were included. Trial activity was more than threefold higher in the recent era, with 393 trials (76.0%) initiated during 2016–June 2025 compared with 124 trials (24.0%) during July 2005–2015. Early development was predominantly diabetes-centered, whereas the later era showed marked expansion into obesity and weight-management, cardiovascular and cardiorenal outcomes, and other emerging indications. Across the mapped corpus, later-phase and larger-enrollment studies became increasingly prominent, reflecting maturation into broader and more pragmatic cardiometabolic development programs. Bibliometric patterns paralleled these shifts, showing a mature diabetes-centered literature and a rapidly expanding obesity evidence community. Over two decades, GLP-1-based therapeutics have transitioned into a broad obesity and cardiometabolic trial ecosystem. These trends are increasingly relevant to bariatric surgeons, particularly in relation to preoperative optimization, postoperative adjunctive therapy, and recurrent weight gain after MBS, and highlight the need for more durable, comparative, and post-bariatric randomized trials.