- A real-world study followed individuals who started GLP-1 medications and discontinued them within 3 to 12 months to assess weight changes after stopping treatment.
- Before stopping the medications, people treated for obesity lost about 8.4% of their body weight, while those treated for type 2 diabetes lost about 4.4% on average.
- One year after discontinuation, average weight regain was small. People in the obesity group regained about 0.5%, while those in the diabetes group lost an additional 1.3% on average, though individual outcomes varied.
- Many people continued other forms of treatment after stopping GLP-1 drugs, which may help explain why large weight regain was not commonly observed.
GLP-1 receptor agonists are medications people may use to manage obesity and type 2 diabetes. These drugs mimic the hormone glucagon-like peptide-1, which helps regulate blood sugar, slow stomach emptying, and reduce appetite.
Two widely prescribed examples include semaglutide and tirzepatide. Both have gained global attention for their ability to potentially aid substantial weight loss. However,
Thus, questions remain about what happens when individuals stop taking these medications. Some research
However, a new study, published in Diabetes, Obesity and Metabolism, indicates that people may maintain much of their weight loss after discontinuation, particularly if they transition to other treatments or lifestyle support.
What are the real-world outcomes of stopping GLP-1s?
In the new retrospective cohort study, researchers from the Cleveland Clinic analyzed electronic health record data from 7,938 adults with overweight or obesity who began injectable semaglutide or tirzepatide between 2021 and 2023.
Participants in the study discontinued treatment within 3 to 12 months, and researchers tracked their weight changes and subsequent treatments for one year after stopping the medication.
The study team compared weight changes among participants who had used the drugs for obesity versus those taking them for type 2 diabetes.
Before discontinuing treatment, individuals treating obesity lost an average of 8.4% of body weight, while those treating type 2 diabetes lost an average of 4.4% of body weight.
After 1 year without the medication, those in the obesity group regained an average of 0.5% of body weight, and those in the diabetes group lost an additional 1.3% of body weight on average.
However, individual outcomes varied. In the obesity group, 55% gained some weight, while 45% maintained or continued losing weight. In the diabetes group, 44% gained weight and 56% maintained or lost weight.
Overall, these results suggest that many people may not experience the large weight regain reported in some randomized clinical trials.
Lead study author, Hamlet Gasoyan, DS, PhD, MPH, a researcher with Cleveland Clinic’s Center for Value-Based Care Research, spoke to Medical News Todayemphasizing the importance of these results in a real-world setting:
“Randomized clinical trials documented that discontinuation of novel obesity medications generally leads patients to regain weight,” Gasoyan told us. “For example, in the SURMOUNT-4 trial, tirzepatide ‘discontinuers’ were randomized to a placebo, and they were unaware whether they were receiving tirzepatide or not.”
“In real-world settings, the most common reasons for discontinuation are cost or insurance-related issues, and side effects, with the former predominating,” he added.
“This is why it is important to understand what additional weight management efforts patients pursue in real-world settings after discontinuing semaglutide or tirzepatide, and whether long-term weight changes after discontinuation follow the patterns reported in randomized clinical trials.”
–Hamlet Gasoyan, DS, PhD, MPH
Why weight regain may be lower in real-world settings
According to the researchers, a potential reason for the difference may be that people often continue their treatment journey in other ways. Within a year of stopping their original medication:
- 27% switched to another obesity medication
- 20% restarted their original drug
- 14% continued treatment through lifestyle interventions, such as visits with dietitians or exercise specialists
- fewer than 1% underwent bariatric surgery.
These treatment adjustments may provide an explanation for why weight regain appeared smaller than previously reported in clinical trials.
Gasoyan added that, “in this large observational study of patients who discontinued semaglutide or tirzepatide, reinitiation of the original medication or receipt of alternative obesity treatment was common, which may explain why they regained less weight than patients in randomized trials.”
Additionally, previous research suggests that GLP-1 drug discontinuation often occurs for practical reasons rather than lack of effectiveness.
For example, insurance coverage may also influence treatment patterns. People using the medications for diabetes were more likely to restart therapy than those taking them for obesity. This is likely because diabetes prescriptions are more consistently covered by insurance.
What the findings mean
The results of this study likely highlight the importance of ongoing, individualized support for people managing obesity and type 2 diabetes.
While
Gasoyan expressed hope that this might help promote conversations between clinicians and individuals:
“For patients who need to stop their GLP-1 RA or dual receptor agonist medication, there are several alternative obesity treatments available. They may want to discuss the available options with their clinician.”
Future research may focus on comparing the effectiveness of different treatments after GLP-1 discontinuation. This could provide guidelines to help clinicians and individuals make informed decisions about long-term weight management.
Commenting on future research, Gasoyan told MNT that “future studies should examine the comparative effectiveness of treatments for obesity in patients who discontinue their novel GLP-1 RA or dual receptor agonist medication.”
“We are already working on the next study, where we examine the comparative effectiveness of alternative treatment options for obesity in patients who discontinue semaglutide or tirzepatide, to help patients and their clinicians make informed decisions. This should inform patient-clinician conversations about alternative options,” he said.
