July 10, 2025
4 min read
Key takeaways:
- Adults who discontinued their obesity medication after less than 1 year lost 3.6% of their body weight.
- Continuing obesity therapy was tied to more than four times higher odds of 10% or greater weight loss.
Adults with obesity were more likely to achieve a 10% or greater weight loss at 1 year if they continued using their prescribed obesity medication, according to findings published in Obesity.
Researchers from Cleveland Clinic analyzed electronic health record data to identify adults with overweight or obesity who used semaglutide (Ozempic/Wegovy, Novo Nordisk) or tirzepatide (Mounjaro/Zepbound, Eli Lilly) from 2021 to 2024. Adults who remained on their prescribed drug for the entire length of follow-up lost significantly more weight at 1 year than those who discontinued their medication.
Hamlet Gasoyan, PhD, health services researcher in the department of internal medicine and geriatrics and investigator at the Center for Value-Based Care Research at Cleveland Clinic and assistant professor of medicine at Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, said weight loss observed in the study was lower than what has been reported in trials for both semaglutide and tirzepatide. He cited discontinuation rates and the use of lower maintenance doses in real-world settings as two contributing factors.
Hamlet Gasoyan
“It’s very important to have discussions about persisting with treatment and being able to get to higher maintenance dosages if one wants to achieve the weight reductions that are advertised on social media or popular media,” Gasoyan told Healio. “What we’ve seen in a real-world setting is those who discontinue particularly early and patients who stay on lower maintenance dosages are quite unlikely to see the weight reductions that are reported in randomized trials. I feel like this will inform the discussions at the very onset of choosing a treatment.”
Gasoyan and colleagues conducted a retrospective cohort study of adults aged 18 years or older with obesity from Cleveland Clinic in Ohio and Florida who started using subcutaneous semaglutide or tirzepatide from 2021 to 2023. Discontinuation of obesity pharmacotherapy was defined as a gap of more than 90 days between the end of the previous supply of the drug and the next prescription dispense. The primary outcome was percentage change in body weight from drug initiation to 1 year. Change in HbA1c from baseline to 1 year was a second primary outcome for adults with prediabetes at baseline.
There were 7,881 adults included in the study (mean age, 51.3 years; 75.2% women), of whom 6,109 were prescribed semaglutide and 1,772 were prescribed tirzepatide. Of the semaglutide group, 21.6% discontinued the medication within the first 3 months of receiving it, 31.4% discontinued it between 3 months and 1 year of their initial prescription fill, and 47% continued the medication through the end of 2024. Of adults prescribed tirzepatide, 16.4% discontinued the medication within 3 months, 34.1% discontinued use at between 3 months and 1 year and 49.4% continued receiving the drug at the end of follow-up.
Weight reduction
Among 6,477 adults with weight available at 1 year, mean weight loss was 8.7%. Adults who discontinued their medication within the first 3 months lost 3.6% of body weight at 1 year, whereas those who discontinued pharmacotherapy at 3 months to 1 year achieved a 6.8% weight loss. Adults who did not discontinue therapy lost a mean 11.9% of their body weight (P < .001).
Adults taking semaglutide lost a mean 7.7% of their body weight at 1 year. Those who continued use of the drug for at 1 year lost 10.9% of their weight. Among those who did not discontinue semaglutide and were on a high maintenance dose, mean weight loss was 14.7% at 1 year.
The tirzepatide group lost a mean 12.4% body weight at 1 year. Weight loss was 15.3% for adults continuing tirzepatide at 1 year. Those who did not discontinue tirzepatide and were on a high maintenance dose lost a mean 18% of their body weight.
(aOR = 1.74; 95% CI, 1.45-2.08) vs. discontinuing use within the first 3 months. The likelihood of achieving 10% or greater weight loss was also higher for adults prescribed tirzepatide vs. semaglutide (aOR = 2.46; 95% CI, 2.16-2.8), those receiving a high dose of a drug vs. a low dose (aOR = 2.39; 95% CI, 2.08-2.75) and for women vs. men (aOR = 1.86; 95% CI, 1.62-2.13).
HbA1c change
There were 895 adults with prediabetes at baseline and HbA1c measurements available at 1 year. Mean HbA1c decrease at 1 year was 0.3 percentage points across all participants. Those who did not discontinue therapy achieved a 0.4 percentage point drop in HbA1c vs. a 0.2 percentage point decrease for adults who discontinued therapy at 3 months to 1 year and a 0.1 percentage point drop for those who discontinued therapy within the first 3 months (P < .001). Mean HbA1c reduction was 0.4 percentage points with tirzepatide and 0.3 percentage points with semaglutide at 1 year.
Of adults with prediabetes, 53.9% achieved normoglycemia at 1 year. The proportion of those who achieved normoglycemia was 67.9% for adults who continued obesity pharmacotherapy, 41% for adults discontinuing therapy between 3 months and 1 year, and 33.1% for adults discontinuing therapy within the first 3 months. Type 2 diabetes was identified in 3.4% of the group. The percentage of adults who developed type 2 diabetes was 6.5% among adults who discontinued therapy in less than 3 months and 4.4% for those discontinuing their medication at 3 months to 1 year vs. 1.7% for adults who continued using their drug through the end of follow-up (P < .001).
Future research
Gasoyan said researchers are conducting another study that will examine the reasons why people discontinued their medication.
“This body of research will really help provide insights on what should go into a conversation between the provider and patient in terms of the challenges with these highly effective medications,” Gasoyan said of future research. “When a decision is to be made on whether someone should get started on [medication] or not, so I feel like this [study] will be very helpful concerning those discussions.”
“We are building evidence that hopefully can be built into prediction models to help patients estimate, based on their individual circumstances, what is the most likely range of weight reduction — given their persistence, BMI, sex, medication they are about to start — at the time of decision-making on which GLP-1 medication to choose, or whether to choose pharmacotherapy or another modality for the treatment of obesity,” Gasoyan said.
For more information:
Hamlet Gasoyan, PhD, can be reached at gasoyah@ccf.org.