Real-World Weight Loss with Semaglutide and Tirzepatide: What Happens When Patients Stop Early? | Research

The takeaway

In nearly 8,000 real-world patients, those who continued semaglutide or tirzepatide for a full year lost 11.9% of their body weight on average, but early discontinuation — which was common — cut results to just 3.6%.

11.9% vs 3.6% Weight Loss
Patients who continued semaglutide or tirzepatide for a full year lost over three times more weight than those who stopped within the first 3 months

What the researchers found

Among 7,881 patients (6,109 on semaglutide, 1,772 on tirzepatide), the mean percentage weight reduction at 1 year was 8.7% overall. Results varied dramatically by discontinuation status:

- Non-discontinuation: 11.9% weight loss (SD 9.2%)

- Late discontinuation (3-12 months): 6.8% weight loss (SD 9.1%)

- Early discontinuation (within 3 months): 3.6% weight loss (SD 8.1%)

All differences were statistically significant (p < 0.001). For patients with prediabetes, glycated hemoglobin (HbA1c) reductions followed the same pattern: 0.4% for continuers, 0.2% for late discontinuers, and 0.1% for early discontinuers. Notably, 80.8% of patients had low maintenance dosages, suggesting most patients were not on the maximum approved doses used in clinical trials.

Why it matters

Clinical trials of semaglutide and tirzepatide showed impressive weight loss (15-20%+), driving massive public interest. But this real-world study reveals a significant efficacy-effectiveness gap — actual results are lower because many patients stop treatment early or never reach maximum doses. This has major implications for patients, prescribers, insurers, and policymakers setting expectations for GLP-1 obesity medications.

How the study worked

Retrospective cohort study using electronic health records from a large health system in Ohio and Florida. Adults with overweight or obesity (without type 2 diabetes) who started injectable semaglutide or tirzepatide between 2021 and 2023 were followed through December 2024. Discontinuation was defined as a >90-day gap between medication supply exhaustion and next dispense, categorized as early (within 3 months) or late (3-12 months).

What this study cannot tell us

Retrospective design using EHR data, which may not capture medications obtained outside the health system or reasons for discontinuation. The study could not account for lifestyle changes, diet, or exercise. Patients without type 2 diabetes were included, so results may not generalize to diabetic populations. The study period overlapped with significant supply shortages for these medications, which may have contributed to discontinuation rates.

How to read the evidence

This is a large retrospective cohort study with nearly 8,000 patients from a real-world clinical setting. While it lacks the controlled conditions of a randomized trial, its large sample size and real-world design provide valuable evidence about how these medications perform outside of clinical trials.

When this study was published

Published in 2025 with data through December 2024, this is one of the most current real-world effectiveness studies of GLP-1 obesity medications, reflecting the period after these drugs became widely prescribed.

The bigger picture

GLP-1 receptor agonists like semaglutide (Wegovy/Ozempic) and the dual GIP/GLP-1 agonist tirzepatide (Mounjaro/Zepbound) are among the most prescribed peptide therapeutics in history. This study provides essential real-world context as these drugs reshape obesity treatment. The finding that most patients are on suboptimal doses and many discontinue early suggests that access barriers (cost, insurance coverage, supply shortages) and side effects significantly limit real-world effectiveness.

Questions still open

What are the primary reasons patients discontinue semaglutide or tirzepatide early — side effects, cost, supply issues, or something else?
Would patients who achieved maximum approved doses show weight loss comparable to clinical trial results?
Do patients who discontinue and restart these medications eventually achieve similar outcomes to continuous users?

Common questions

Why is real-world weight loss with Wegovy and Zepbound lower than in clinical trials?

This study found two main reasons: many patients stop taking the medication early (within 3-12 months), and most patients (80.8%) were on lower doses than the maximum used in clinical trials. Clinical trials also have stricter adherence monitoring and patient support. Patients who did stay on treatment for a full year averaged 11.9% weight loss, closer to trial results.

How important is it to keep taking semaglutide or tirzepatide long-term?

Very important according to this study. Patients who continued treatment for a full year lost 11.9% of their body weight on average, while those who stopped within 3 months lost only 3.6%. Glycemic improvements followed the same pattern. This suggests that consistent, long-term use is critical for achieving meaningful results with these GLP-1-based obesity medications.

Read the original research

Changes in weight and glycemic control following obesity treatment with semaglutide or tirzepatide by discontinuation status.

Obesity (Silver Spring, Md.), 33(9), 1657-1667

View on PubMed ↗Publisher’s paper ↗

Citation

Gasoyan, Hamlet; Butsch, W Scott; Schulte, Rebecca; Casacchia, Nicholas J; Le, Phuc; Boyer, Christopher B; Griebeler, Marcio L; Burguera, Bartolome; Rothberg, Michael B. (2025). Changes in weight and glycemic control following obesity treatment with semaglutide or tirzepatide by discontinuation status.. Obesity (Silver Spring, Md.), 33(9), 1657-1667. https://doi.org/10.1002/oby.24331