Switching GLP-1 Medications May Improve Long-Term Engagement in Obesity Treatment, Real-World Study Suggests
Key Takeaways:
- Real-world data from nearly 127,000 adults with overweight or obesity found that switching between GLP-1 receptor agonist medications was associated with greater long-term treatment persistence.
- Only about one quarter of patients remained on any GLP-1 therapy after one year, highlighting ongoing challenges with long-term adherence.
- Researchers suggest that changing medications should be viewed as a normal part of obesity care, rather than as a sign that treatment has failed.
Large real-world study examines how patients use GLP-1 medications
Patients without diabetes who switched between glucagon-like peptide-1 receptor agonist (GLP-1RA) medications for overweight or obesity were more likely to remain engaged with treatment than those who stayed on the same medication, according to new research conducted by investigators at UT Southwestern Medical Center.
The findings were published in JAMA Network Open and provide one of the most detailed real-world analyses to date of how adults with overweight or obesity use these medications over time. The study suggests that switching between drugs within the same therapeutic class is relatively common and may play an important role in sustaining long-term treatment.
The researchers argue that clinicians should not interpret medication changes as treatment failure. Instead, they suggest that switching therapies may represent a pragmatic strategy to maintain continuity of care when patients experience side effects, access issues, or other barriers.
“This study provides one of the largest real-world descriptions to date of how adults with overweight or obesity use and switch GLP-1RAs over time,” said first author Luyu (Amber) Xie, Ph.D., Pharm.D., Assistant Professor in the Peter O’Donnell Jr. School of Public Health and co-Director of the Biostatistics and Data Science Core at UT Southwestern. “It highlights that long-term persistence is low and that switching between medications is a relatively common part of ongoing treatment rather than a sign of failure.”
Tracking medication use in nearly 127,000 adults
To examine treatment patterns, the research team analysed insurance claims data from nearly 127,000 adults in the United States who were living with overweight or obesity and initiated GLP-1RA therapy between 2019 and 2024.
Participants in the study did not have diabetes and were prescribed GLP-1 medications specifically for weight management. The researchers tracked medication use over a 12-month period following treatment initiation in order to understand how patients continued, discontinued, or switched therapies.
The analysis revealed that treatment pathways were rarely straightforward. Instead of remaining on a single medication for the entire year, many patients experienced adjustments to their treatment regimen. These changes were often driven by factors such as side effects, medication availability, insurance coverage, and the introduction of newer therapies.
GLP-1 receptor agonists have become a central component of modern obesity treatment. Medicines in this class include semaglutide, liraglutide, and tirzepatide, all of which act on hormonal pathways involved in appetite regulation and metabolic control. Despite their clinical effectiveness, maintaining long-term adherence has proven difficult for many patients.
Persistence remains a major challenge
The study found that long-term persistence with GLP-1RA therapy remains relatively low.
After one year, only around one quarter of patients remained on any GLP-1 medication. During that same period, approximately one in five patients transitioned from their initial therapy to a different GLP-1RA.
However, the data also revealed an important pattern. Patients who switched medications were more likely to continue treatment overall and demonstrated higher levels of adherence compared with those who remained on their original therapy.
These findings suggest that medication switching may reflect proactive clinical management rather than treatment failure.
“Switching between GLP-1RA medications should be viewed as a normal part of long-term obesity care,” said senior author Sarah Messiah, Ph.D., M.P.H., Professor of Epidemiology and Pediatrics, Associate Dean for Research in the O’Donnell School of Public Health, and Director of the Child and Adolescent Population Health Program. “Persistence should not be judged by staying on a single drug indefinitely, but by maintaining engagement in care and working with clinicians to find sustainable, effective treatment strategies over time.”
Visualising treatment pathways
In addition to analysing persistence and switching rates, the researchers also mapped treatment pathways to illustrate how patients moved between different medications over the course of the study period.
These visualisations showed that newer once-weekly injectable therapies frequently served both as initial treatments and as destinations when patients switched from other medications. This pattern reflects the growing role of these agents in contemporary obesity management.
According to the researchers, these dynamic treatment pathways highlight the evolving nature of obesity pharmacotherapy and reinforce the need for flexible treatment strategies.
“In today’s clinical environment, successful obesity care often involves adapting treatment over time rather than expecting a single medication to meet every patient’s needs indefinitely,” said co-author Jaime Almandoz, M.D., M.B.A., Professor of Internal Medicine in the Division of Endocrinology and Medical Director of UTSW’s Weight Wellness Program.
Setting realistic expectations in obesity care
The findings also underline the importance of setting realistic expectations with patients at the start of treatment.
Clinicians may need to emphasise that finding the most effective long-term medication strategy can involve trial and adjustment. In some cases, more than one medication may be prescribed before a sustainable approach to treatment is established.
By framing medication adjustments as part of routine care, clinicians may help patients remain engaged with treatment and reduce the perception that a change in therapy represents a setback.
Future research on personalised treatment pathways
The authors note that additional research is needed to better understand the factors that shape treatment trajectories in obesity care.
Future work will explore how patient characteristics, specific medications, and the timing of therapy influence patterns of persistence and switching. The goal is to generate insights that can support more personalised and sustainable approaches to treatment.
Study contributors and funding
Additional UT Southwestern researchers involved in the study include Diego Anazco Villarreal, M.D., an Internal Medicine resident; Azucena Herrera Chancay, M.D., an Internal Medicine fellow; M. Sunil Mathew, M.S., Senior Population Science Data Manager; and Jackson Francis, M.P.H., Population Science Project Coordinator.
The research was supported by the UTSW Clinical and Translational Science Award, the National Institutes of Health (1U54TR00236), the Texas Health Resource Clinical Scholar program, and the UTSW Nutrition & Obesity Research Center (NORC).
CCH insight:
This is an interesting study which looks at a very important issue. Obesity is a chronic relapsing disease so ongoing, long-term treatment is necessary. If a patient is struggling with a particular medication, the opportunity to try an alternative is very helpful, and will increase the chances of adhering to treatment. The number of options is gradually increasing, most notably with oral formulations becoming available this year, and new drugs in the pipeline such as petrelintide, which promises slightly less weight loss than Wegovy or Tirzepatide, but minimal gastrointestinal side effects – so far better tolerability. All these developments should help patients find a medication that works for them, enabling long-term treatment compliance and better outcomes.
