Clinical trials
STEP 5: two-year semaglutide results
Most weight-loss drug trials run about a year. STEP 5 asked whether the effect lasts two.
Quick Answer
STEP 5 (Nat Med, 2022) followed adults with obesity on once-weekly semaglutide 2.4 mg for 104 weeks (two years). Mean weight reduction was about 15.2% with semaglutide versus about 2.6% with placebo, showing the effect is sustained over the longer term with continued treatment. Compounded semaglutide is not FDA-approved.
Key Facts
- Two-year (104-week) trial in adults with obesity
- Mean weight change: about −15.2% (semaglutide) vs −2.6% (placebo)
- Weight loss was sustained, not regained, while treatment continued
- Reinforces obesity as a chronic, treat-to-maintain condition
- Studied the branded product; compounded semaglutide is not FDA-approved
Why a two-year trial matters
Many obesity drug trials run about 68 weeks, leaving open whether results last. STEP 5 extended follow-up to two years, testing durability of semaglutide 2.4 mg with continued treatment and lifestyle support.
The results
Mean weight reduction was about 15.2% with semaglutide versus 2.6% with placebo at two years — similar to the one-year STEP 1 result, indicating the loss was largely maintained rather than regained while treatment continued. This is important because the body tends to defend a higher weight over time.
What it adds
Together with STEP 4 (which showed regain after stopping), STEP 5 supports a treat-to-maintain model: continued treatment sustains the benefit, while stopping tends to reverse it. Longer-term safety and outcomes continue to be studied.
Caveats
Averages hide individual variation, and the branded product was studied. Compounded semaglutide is not FDA-approved. Decisions about long-term treatment are individual and clinician-led.
Frequently asked questions
Does semaglutide keep working after a year?
In STEP 5, weight loss was sustained at about 15.2% over two years with continued treatment, similar to the one-year result.
Will I regain if I stop after two years?
STEP 5 studied continued treatment; STEP 4 and other data show stopping tends to be followed by substantial regain. Plan any stop with a clinician.
References
- Garvey WT, et al. Two-year effects of semaglutide in adults with overweight or obesity (STEP 5). Nat Med. 2022;28:2083-2091.
- Rubino D, et al. Effect of continued vs withdrawn semaglutide on weight maintenance (STEP 4). JAMA. 2021;325:1414-1425.
- U.S. Food and Drug Administration. Wegovy, Ozempic and Rybelsus (semaglutide) prescribing information. Novo Nordisk.
Citations are for educational reference; this article summarizes published research in plain language and is not medical advice.
Bottom Line
STEP 5 showed semaglutide's ~15% weight loss is sustained over two years with continued treatment — supporting a long-term, treat-to-maintain approach.