Treatment of Obesity with GLP-1 Receptor Agonists - An Outcome Mapping Review

Abstract Background. Obesity is a global health challenge, with its prevalence more than doubling over the last three decades. While lifestyle modifications and bariatric surgery are standard treatments, pharmacological interventions, specifically GLP-1 Receptor Agonists (GLP-1 RAs), have emerged as critical options for sustained weight management. Objectives. This outcome mapping review aims to systematically identify and categorize outcomes reported in clinical trials on the treatment of obesity with GLP-1 RAs, with a specific focus on Semaglutide, Liraglutide, and Tirzepatide. Eligibility Criteria. Adults aged ≥18 years with obesity (BMI ≥30 kg/m²) receiving GLP-1 RAs (Semaglutide, Liraglutide, or Tirzepatide) compared to placebo, active comparators, or lifestyle interventions in Phase 2 through 4 RCTs. Outcomes include weight change, cardiovascular events, quality of life, and safety signals (gastrointestinal, pancreatic, hepatic, renal, and thyroid events). The search is open to all languages (assisted by DeepL AI translation) and includes studies published from inception until June 1st, 2026. Information Sources and Search Strategy. The literature search will be conducted in three sequential phases. First, a comprehensive keyword-based search will be performed across major bibliographic databases including PubMed/MEDLINE, Scopus, Web of Science, and Cochrane Library. To minimize publication bias, gray literature and trial registries - including ClinicalTrials.gov, PROSPERO, the Open Science Framework (OSF), and Zenodo - will be systematically searched. Following the initial database search, a forward citation search will be conducted to identify relevant meta-analyses and systematic reviews that cite the included studies. Finally, a snowball search will be performed using reference lists from identified relevant studies to capture additional sources not retrieved through the earlier search phases. Synthesis. Data will be synthesized through an outcome mapping approach to provide an overview of outcomes grouped into categories, such as weight-related outcomes, cardiovascular disease/risk outcomes, glycemic control outcomes, lipid, renal and hepatic outcomes, and quality of life outcomes, as efficacy/beneficial outcomes. Gastrointestinal adverse events, pancreatic events, hepatobiliary events, cardiovascular events, 3-point MACE (Major adverse cardiovascular events), renal events, local tolerability, and thyroid safety signals, as safety/adverse events. Contribution. This review, conducted as part of a diploma thesis at the University of Split - School of Medicine, will provide a comprehensive map of the evidence landscape for specific GLP-1 RAs in obesity. The findings will help researchers and clinicians understand the breadth of reported outcomes throughout study phases, will facilitate meta-analytic syntheses, and identify gaps in evidence. Keywords: Obesity; Glucagon-Like Peptide-1 Receptor Agonists; Anti-Obesity Agents; Weight Loss; Treatment Outcome.