Not Everyone Responds the Same Way to GLP-1 Medications

When you read about weight-loss medications, you usually see the average result. Averages are useful, but they hide something important: people respond very differently. Some lose a lot, some lose a little, and some do not lose much at all. This guide looks at how wide that range was in the large semaglutide trial known as STEP 1, and why it matters for expectations. It is general education, not medical advice.

The average, and what sits behind it

In STEP 1, published in the New England Journal of Medicine in 2021 by John Wilding and colleagues, about 1,960 adults with overweight or obesity (and without diabetes) were randomly assigned to weekly semaglutide or a placebo, alongside lifestyle counseling. After 68 weeks, the average weight change was about a 15 percent loss with semaglutide, compared with about 2.4 percent with placebo.

How the results were spread out

The trial also reported the share of people reaching different thresholds of weight loss at 68 weeks:

• 5 percent or more: about 86 percent on semaglutide, compared with about 32 percent on placebo.
• 10 percent or more: about 69 percent, compared with about 12 percent.
• 15 percent or more: about 50 percent, compared with about 5 percent.

Put the other way around, around one in seven people on the medication did not reach 5 percent, and about half did not reach 15 percent. Individual results ran from very little to a great deal.

Why people respond differently

• Biology. Appetite hormones, gut signals and genes vary from person to person. Our guide to the hormones behind hunger explains some of the system involved.
• Side effects and tolerance. Some people need to adjust or stop because of digestive effects. See side effects in the big trials.
• Starting point. People with higher starting weights may lose more kilograms, while percentage losses can look similar.
• Habits and support. Eating patterns, sleep, activity and counseling all play a part.
• Medical conditions and other medicines. These can influence how someone responds.

What the trial does not tell us

• It was a trial with close support. Everyone received lifestyle counseling, which may be more than typical care.
• It does not predict any one person. There is no reliable way yet to say who will lose more.
• It was 68 weeks. What happens after that, including after stopping, is covered in our guide to stopping a GLP-1 medication.
• Weight is one measure. Blood pressure, blood sugar and how people feel also matter.

Keeping expectations kind

• Treat the average as a headline, not a promise. Your result may be higher or lower.
• Judge progress in several ways. Energy, strength, sleep and numbers from your clinician tell more of the story.
• Protect muscle. Our guide to muscle loss on GLP-1 medications explains why strength work matters.
• Talk with your prescriber about what is realistic for your situation.

In short

Large trials show real, substantial average benefits, and also a wide spread of individual results. Knowing that can make the process less discouraging if your own path looks different from the headline number.

Sources

• Wilding JPH, Batterham RL, Calanna S, et al. Once-weekly semaglutide in adults with overweight or obesity. New England Journal of Medicine, 2021;384(11):989-1002 (STEP 1).