Study ties lower real-world weight loss to stopping semaglutide or tirzepatide early

Adults who started injectable semaglutide (sold as Ozempic and Wegovy) or tirzepatide (sold as Mounjaro and Zepbound) lost an average of 8.7% of their body weight after one year. The average was 11.9% among those who stayed on treatment and 3.6% among those who stopped within three months, according to a Cleveland Clinic study published in the journal Obesity ^[1].

The study is a retrospective cohort analysis of electronic health records from a large health system in Ohio and Florida. It included 7,881 adults with overweight or obesity who did not have type 2 diabetes and who started injectable semaglutide or tirzepatide between 2021 and 2023. Of those, 6,109 received semaglutide and 1,772 received tirzepatide ^[1]. The researchers tracked weight through 12 months and, in patients who had prediabetes at the start, A1c, with follow-up ending in December 2024 ^[1].

Discontinuation was defined as a gap of more than 90 days between running out of a supply and the next fill. Early discontinuation meant stopping within three months of starting; late discontinuation meant stopping between three and 12 months ^[1]. One-year weight loss averaged 3.6% (standard deviation 8.1) with early discontinuation, 6.8% (SD 9.1) with late discontinuation and 11.9% (SD 9.2) among patients who did not discontinue (p < 0.001) ^[1]. Dosing in the group was also lower than in trials: 80.8% of patients were on low maintenance doses ^[1].

Among the 1,320 patients with prediabetes at baseline, A1c fell by an average of 0.1 percentage points with early discontinuation, 0.2 points with late discontinuation and 0.4 points among those who stayed on treatment (SD 0.4 in each group; p < 0.001) ^[1].

The authors write that average weight loss in this cohort was lower than in the main phase 3 trials, the randomized studies that supported approval of the drugs, and that the gap was likely due to higher rates of discontinuation and lower maintenance doses ^[1].

Why it matters for patients

Trial results describe what happened under controlled conditions, with scheduled follow-up and doses that were often raised on a set schedule. This study describes what happened in one health system's routine care, where the average included people who stopped early ^[1].

Two things stand out for anyone weighing these drugs or already taking them. First, the results are group averages, and the standard deviations are nearly as large as the averages themselves, meaning individual results ranged widely in both directions ^[1]. Second, the study does not report why patients stopped. Side effects, cost, insurance coverage and supply problems are not analyzed here, so the reasons for discontinuation have not been reported ^[1].

Because the study is observational, it cannot prove that stopping caused the smaller weight loss, though the pattern is consistent with the randomized trials, where results also depended on staying on treatment ^[1]. The study also does not say whether patients regained weight after stopping or later restarted treatment; those outcomes have not been reported ^[1].

The data come from one health system in Ohio and Florida, so results may differ in other regions and populations. Results by insurance status, income or race were not reported ^[1]. It also is not known from this study which doses individual patients reached, or how those decisions were made.