GLP-1 real-world weight loss falls short of trial results

Study results

The retrospective cohort study analyzed electronic health records of 7,881 adults with severe obesity (body mass index over 39) treated between 2021 and 2023 across the Cleveland Clinic Health System.

Real-world weight loss outcomes correlated closely with treatment persistence and dosing. For instance, the patients who discontinued GLP-1 treatment early lost an average of 3.6% body weight after one year, while late discontinuers lost 6.8%.

Patients who stayed on therapy for a full year saw an average weight loss of 11.9%, falling short of the 15–20% typically observed in randomized clinical trials. However, among those who consistently used higher doses, weight loss with semaglutide reached 13.7% and tirzepatide 18%, coming closer to trial results.

Key factors linked to greater GLP-1 weight loss

According to the study, several key factors improved the chances of achieving at least 10% weight loss with GLP-1 therapy after one year in a real-world setting, including the following:

• Continuous treatment or late discontinuation of therapy. Stopping early led to less weight loss.
• Using tirzepatide instead of semaglutide. Tirzepatide showed greater weight loss results.
• Higher drug dosages. Patients on higher drug dosages lost more weight.
• Female sex. Women responded better than men.

Metabolic outcomes mirrored this pattern as well. Among 1,320 patients with prediabetes, hemoglobin A1c normalization (≤5.6%) was achieved by 33% of early discontinuers, 41% of late discontinuers and 67.9% of those who maintained therapy.

"Our study shows that patients treated for obesity with semaglutide or tirzepatide lost less weight on average in a regular clinical setting compared to what is observed in randomized clinical trials," lead author Hamlet Gasoyan, Ph.D., M.P.H, of the Cleveland Clinic's Center for Value-Based Care Research, said in a news release. "This was mainly due to higher rates of discontinuation and lower maintenance dosages used in clinical practice."

Why patients stop GLP-1 therapy

The study also identified key reasons driving early GLP-1 treatment discontinuation:

• High out-of-pocket costs and insurance barriers.
• Side effects.
• Drug supply shortages.

These findings highlight the need for patient education and support programs that improve GLP-1 therapy adherence and dose escalation. As the study noted, addressing cost, coverage and supply issues must be overcome to ensure real-world outcomes match the clinical promise of GLP-1 therapies for weight loss.

Alivia Kaylor is a scientist and the senior site editor of Pharma Life Sciences.