Important Note This article is for educational purposes only. It does not constitute medical advice.
The STEP (Semaglutide Treatment Effect in People with Obesity) clinical trial programme is one of the most extensive research efforts conducted on semaglutide for weight management. These trials were designed to evaluate how effective and safe semaglutide is when used for weight loss in people with overweight or obesity, with or without other health conditions.
This page provides a clear overview of the STEP programme and its key findings.
What Was the STEP Programme?
The STEP programme consisted of multiple Phase 3 clinical trials. Each trial had a slightly different focus, but together they aimed to answer important questions about semaglutide’s role in weight management. The main objectives of the STEP trials included:
- Measuring average weight loss
- Evaluating improvements in heart health markers
- Assessing effects on blood sugar control
- Understanding how well people tolerated the medicine over time
- Studying weight maintenance after stopping treatment
Overview of Key STEP Trials
| Trial | Focus | Key Results | Duration |
|---|---|---|---|
| STEP 1 | Weight loss in people with obesity/overweight | Average ~15% weight loss | 68 weeks |
| STEP 2 | Weight loss in people with type 2 diabetes | Average ~10% weight loss | 68 weeks |
| STEP 3 | Weight loss with intensive behavioural therapy | Average ~16% weight loss | 68 weeks |
| STEP 4 | Weight maintenance after initial weight loss | Continued weight loss with ongoing treatment | 68 weeks |
| STEP 5 | Long-term weight management (2 years) | Sustained weight loss over 104 weeks | 104 weeks |
These trials involved thousands of participants across multiple countries and provided robust data on semaglutide’s effects.
Key Findings from the STEP Trials
Weight Loss Results In STEP 1, participants taking semaglutide 2.4 mg once weekly lost an average of about 15% of their body weight over 68 weeks, compared to roughly 2.4% in the placebo group. A large proportion of participants achieved clinically meaningful weight loss (10% or more).
Effects in People with Type 2 Diabetes STEP 2 showed that semaglutide was also effective for weight loss in people who had both overweight/obesity and type 2 diabetes, although the average weight loss was slightly lower than in people without diabetes.
Weight Maintenance STEP 4 and STEP 5 demonstrated that continuing semaglutide treatment helped people maintain or further reduce their weight. When treatment was stopped, many participants regained weight, suggesting that ongoing treatment may be needed for long-term weight management in some people.
Additional Health Benefits Across the trials, semaglutide was associated with improvements in several health markers, including better blood sugar control, reductions in blood pressure, and improvements in cholesterol levels.
How Was Semaglutide Dosed in the STEP Trials?
In most STEP trials, participants started at a low dose of semaglutide and gradually increased it over several weeks. This gradual dose escalation was used to help reduce gastrointestinal side effects. The target dose in most weight management trials was 2.4 mg once weekly. Some participants who could not tolerate the full dose remained on lower doses (1.7 mg or 1.0 mg).
Side Effects Observed in the STEP Trials
The most common side effects reported were gastrointestinal, including:
- Nausea
- Vomiting
- Diarrhoea
- Constipation
These effects were usually mild to moderate and occurred mainly during the dose escalation period. Discontinuation rates due to side effects were relatively low (around 7% in STEP 1), and many people were able to continue treatment after dose adjustments.
What the STEP Trials Tell Us
The STEP programme provided strong evidence that semaglutide can produce meaningful and sustained weight loss when combined with lifestyle changes. It also showed that the medicine is generally well tolerated, although gastrointestinal side effects are common, especially early in treatment.
The trials also highlighted that weight regain is common after stopping semaglutide, which has implications for long-term treatment strategies.
Limitations of the STEP Trials
While the STEP programme was large and well-designed, it had some limitations:
- Most trials lasted between 68 and 104 weeks. Longer-term data is still being collected.
- Participants received structured lifestyle support alongside the medicine.
- Individual results varied widely — not everyone achieved the average weight loss seen in the trials.
Summary
The STEP clinical trial programme demonstrated that semaglutide 2.4 mg once weekly can lead to significant weight loss (around 15% on average) in people with overweight or obesity. The trials also showed improvements in several cardiometabolic risk factors and highlighted the importance of gradual dose escalation to improve tolerability. While semaglutide is effective for many people, results vary, and ongoing treatment appears necessary for maintaining weight loss in most cases. As of 2026, semaglutide remains one of the most well-studied medicines in this class.
References
- ClinicalTrials.gov – STEP Programme (Semaglutide). NCT03548987 and related entries.
- Wilding, J.P.H. et al. (2021). Once-Weekly Semaglutide in Adults with Overweight or Obesity. New England Journal of Medicine.
- Rubino, D. et al. (2022). Effect of Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity. JAMA.
- Medicines and Healthcare products Regulatory Agency (MHRA) – Guidance on GLP-1 receptor agonists.
For more information, see our main guide on Semaglutide and our comparison article Semaglutide vs Tirzepatide.
Last Updated: July 2026