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While still limited, real\u2010world studies on GLP\u20101RA use in populations with obesity are increasingly available. This narrative review discusses contemporary real\u2010world evidence demonstrating the utilization, clinical and comparative effectiveness, and adverse effects of the currently approved GLP\u20101RA\u2010based weight\u2010loss therapies, that is, liraglutide, semaglutide and tirzepatide. The observed weight reduction in clinical practice overall tends to be lower than in randomized controlled trials; however, outcomes approach those seen in trials when focusing on highly adherent patients. Real\u2010world studies demonstrate high discontinuation rates of GLP\u20101RAs (20%\u201350%) within the first year, and the use of much lower doses than those evaluated in clinical trials. Evidence from observational studies within type 2 diabetes or obesity populations suggests frequent gastrointestinal disturbances in GLP\u20101RA users, as also observed in trials, but no clear increase in risks of severe events like pancreatitis or pancreatic cancer, thyroid disorders, or depression and self\u2010harm. Further evidence is needed to understand possible real\u2010world associations of GLP\u20101RAs with eye disease and other rare outcomes. We provide 10 areas of particular importance for further research on GLP\u20101RA within the real\u2010world space, including improved understanding of the exact drivers of early discontinuation and suboptimal dosing, studies of the effects of stopping GLP\u20101RA treatment, and investigations of clinical and cost\u2010effectiveness for hard clinical outcomes in real\u2010world settings, including not only cardio\u2010reno\u2010metabolic outcomes but also obesity\u2010induced diseases like neuropsychiatric disease, cancer, musculoskeletal disease, and infections.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Plain Language Summary<\/jats:title>\n                    <jats:p>Recent advancements in weight\u2010loss medications have sparked a lot of interest. The so\u2010called GLP\u20101 receptor agonist medications (GLP\u20101RAs) have gained a lot of attention, because they have shown to be very effective, leading to significant weight loss in patients participating in clinical trials. GLP\u20101RAs, like liraglutide, semaglutide, and tirzepatide, help manage weight by mimicking hormones that control blood sugar and appetite. However, how these medications perform in real life can be different from the controlled settings of clinical trials, in which patients are carefully selected and their treatment plans closely followed. This literature review looks at how these medications are used and their effectiveness and safety in real\u2010world settings. In real\u2010life practice, GLP\u20101RAs are often less effective than in clinical trial conditions. This is usually because patients don't follow their medication plans as strictly as in trials. Real\u2010world data shows that many patients use lower doses and do not stick to their treatment as strictly as participants in a controlled trial might, leading to less weight loss. However, those who do follow their plans closely can achieve results similar to those in trials. A major issue with GLP\u20101RAs is that many patients stop using them within the first year due to side effects or high costs of the medications, especially if not covered by insurance. Common side effects include nausea and digestive problems, which are the main reasons patients stop taking these treatments. These side effects are often manageable and decrease over time, and this reviews found no strong real\u2010world evidence that GLP\u20101RAs cause severe side effects in many users. Despite these challenges, when GLP\u20101RAs are used effectively and consistently, they show substantial benefits in weight loss, most so the newest medications semaglutide and tirzepatide. These medications are also likely to help manage and prevent weight\u2010related health conditions like type 2 diabetes and cardiovascular disease, but evidence for these beneficial outcomes is still scarce in real\u2010world settings. The review emphasizes the need for more research to understand why many patients stop using these medications and how to improve dosing. It also calls for studies on the long\u2010term effects of these therapies on various health outcomes, including mental health, cardiometabolic health, cancer, and rare conditions like eye diseases. Overall, while GLP\u20101RAs are a valuable tool for weight management, their real\u2010world use requires careful consideration of individual patient factors, such as the ability to stick to treatment plans, manage side effects, and afford the medications. Further research will help make these treatments more effective for a wider range of people that need them.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.16364","type":"journal-article","created":{"date-parts":[[2025,4,8]],"date-time":"2025-04-08T08:11:07Z","timestamp":1744099867000},"page":"66-88","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":214,"title":["Real\u2010world evidence on the utilization, clinical and comparative effectiveness, and adverse effects of newer\n                    <scp>GLP<\/scp>\n                    \u2010\n                    <scp>1RA<\/scp>\n                    \u2010based weight\u2010loss therapies"],"prefix":"10.1111","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9135-3474","authenticated-orcid":false,"given":"Reimar W.","family":"Thomsen","sequence":"first","affiliation":[{"name":"Department of Clinical Epidemiology Aarhus University and Aarhus University 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