The STEP Trials: Semaglutide's Weight Management Evidence

Part of the DietApp.com GLP-1 Trial Database, a comprehensive, regularly reviewed resource.

What It Is

STEP, Semaglutide Treatment Effect in People with Obesity, is the clinical trial program that established semaglutide's effectiveness for chronic weight management. STEP 1, published in the New England Journal of Medicine in 2021, is the landmark trial in the series and formed the primary basis for Wegovy's FDA approval.

Key Results

STEP 1 showed an average weight loss of 14.9% of body weight at 68 weeks in adults with overweight or obesity, without diabetes, taking semaglutide 2.4 mg weekly alongside lifestyle intervention. Subsequent trials in the series, including STEP 3, examined semaglutide combined with more structured behavioral support, which showed even greater average weight reduction than semaglutide alone.

Side Effects Observed

The dominant side effects across the STEP trials were gastrointestinal, primarily nausea, constipation, and fatigue, occurring mainly during dose escalation. Serious adverse events were uncommon, and the trials did not identify an increased risk of pancreatitis or thyroid tumors in humans, though the boxed warning based on rodent studies remains part of semaglutide's label as a precaution.

What Happens After Stopping

STEP 1 extension data found that participants who stopped semaglutide regained roughly two-thirds of their lost weight within a year, evidence that's directly informed the general understanding that GLP-1 medications function more like a long-term treatment, similar to blood pressure medication, than a short-course fix.

References

• Wilding JPH et al., STEP 1 Trial, NEJM 2021
• Medicspot: GLP-1 Clinical Trials Summary
• FormBlends: Clinical Trial Summary, SELECT

Related Resources

• Semaglutide Medication Guide
• Wegovy Medication Guide

Related Articles

• The SURMOUNT Trials
• The SELECT Trial
• Will I Regain Weight If I Stop Taking My GLP-1 Medication?

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About DietApp.com

DietApp.com combines evidence-based GLP-1 medication education with practical treatment tracking tools. The information on DietApp.com is intended for educational purposes only and should not replace professional medical advice, diagnosis, or treatment.

Last medically reviewed and updated: July 11, 2026.