Injectable GLP-1 drugs like semaglutide and tirzepatide may produce smaller weight loss in a “real-world” setting because patients may be more prone to discontinue treatment or use lower maintenance dosages than was used in clinical trials, according to recently published study results.1
Led by Hamlet Gasoyan, PhD, and other researchers from Cleveland Clinic’s Center for Value-Based Care Research, the retrospective study examined these medications’ effect on weight reduction and glycemic control in a real-world setting of 7881 adult patients with an average body mass index >39. Among the participants, 1320 had prediabetes at the start of the study, defined by blood sugar levels between 5.7% and 6.4%.
The study participants began treatment for obesity with injectable forms of semaglutide or tirzepatide between 2021 and 2023. The researchers grouped patients who discontinued their obesity medications into those who discontinued within 3 months of treatment and those who discontinued within 3 to 12 months. The study’s follow-up ended in December 2024.
The researchers noted that >20% of patients discontinued their medications early and 32% discontinued their medications late. In addition, >80% of study participants were on lower maintenance dosages of those medications. The maintenance dose refers to the amount of medication needed to sustain a therapeutic effect.
One year after the treatment start, the researchers noted that the average weight reduction was 3.6% among the participants who discontinued their treatment early, compared with 6.8% for those who discontinued their treatment late. Those who did not discontinue treatment lost on average 11.9% of their body weight. Those who did not discontinue treatment and were on a high maintenance dosage of the medications lost 13.7% of their body weight with semaglutide and 18.0% with tirzepatide.
“Our findings about the real-world use patterns of these medications and associated clinical outcomes could inform the decisions of healthcare providers and their patients on the role of treatment discontinuation and maintenance dosage in achieving clinically meaningful weight reductions,” Gasoyan said in a press release about the findings.2
Researchers also identified what factors were associated with higher odds of achieving weight loss of ≥10%. Patients had higher odds of achieving ≥10% weight reduction after 1 year of treatment if they:
- Did not discontinue their medications or discontinued late (vs early)
- Were on high maintenance dosage
- Received tirzepatide (vs semaglutide)
- Were female (vs male)
Among the participants with prediabetes, 33% of those who discontinued their treatment early experienced normal blood sugar levels (defined by HbA1c levels ≤5.6), compared with 41% who discontinued their treatment late, and 67.9% who did not discontinue treatment.
The most common reasons for discontinuation of treatment included the cost of the medications and insurance coverage, and medication shortages. A follow-up study is in the works to quantify why patients discontinue their obesity medications in a real-world setting.
In addition, the researchers noted those patients who discontinued their obesity medications lost significantly less weight when compared with those who remained on the medications. This will be studied further to identify what additional weight management methods patients are using in real-world settings after discontinuation of obesity medications.
Semaglutide Discontinuation in Veterans
Findings that were published separately but within weeks of the Cleveland Clinic findings at the 85th Scientific Sessions of the American Diabetes Association (ADA) shed some light into additional weight management methods following semaglutide discontinuation in a veteran population.3
In that study, which examined data from people who did not have diabetes but initiated semaglutide from 2019 to 2024, 2403 had concurrent lifestyle interventions (LI) enrollment, defined as participating in the VA MOVE! program within 6 months of treatment initiation.
These individuals were matched 1:3 to those without LI. The study noted that those people “with concurrent LI achieved greater weight loss before semaglutide discontinuation (-8.3% vs. -7.4%, P<0.001).” One year of follow-up data demonstrated that net weight loss remained greater among the LI group. “These findings underscore the importance of integrating LI with semaglutide therapy to enhance long-term weight management,” the researchers writing in that study concluded.
According to other data presented during the ADA meeting, participants in the VA MOVE! program had a reduced incidence of type 2 diabetes over 15 years, although subgroup type influenced outcomes over time.4
References
- Gasoyan H, Butsch WS, Schulte R, et al. Changes in weight and glycemic control following obesity treatment with semaglutide or tirzepatide by discontinuation status. Obesity. 2025;1-11.
- Cleveland Clinic. Cleveland Clinic Research finds injectable medications for obesity produce smaller weight loss in a real-world setting compared to randomized clinical trials [press release]. June 10, 2025. Accessed June 30, 2025. https://newsroom.clevelandclinic.org/2025/06/10/cleveland-clinic-research-finds-injectable-medications-for-obesity-produce-smaller-weight-loss-in-a-real-world-setting-compared-to-randomized-clinical-trials
- Xue Q, Li P, Station E, et al. Weight loss maintenance following semaglutide discontinuation—the role of concurrent lifestyle intervention. 85th Scientific Sessions of the American Diabetes Association. June 20-23, 2025; Chicago, IL. 2199-LB.
- Li P, Shao H, Xue Q, et al. Assessing the real-world effectiveness of the VA MOVE! Lifestyle Program in preventing type 2 diabetes—a 15-year follow-up study [Board No. 160]. 85th Scientific Sessions of the American Diabetes Association. June 20-23, 2025; Chicago, IL. 160-OR.