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STEP 1 · Wilding et al. · NEJM 2021

86% of participants crossed the threshold that actually matters.

Five percent body-weight loss is the level where blood pressure, blood sugar, and cardiovascular risk start to measurably improve. Most of the semaglutide arm got there.

Average weight loss is one way to read a trial. Responder rate — the percentage of participants who actually crossed a clinically meaningful threshold — is often a more useful one. It tells you how often the medication "worked," not just how big the average was.

In STEP 1, the responder thresholds were ≥5%, ≥10%, ≥15%, and ≥20% body-weight loss from baseline. The 5% mark is widely cited in the obesity-medicine literature as the point at which weight-related health risks (blood pressure, glycemic control, lipids, sleep apnea, joint pain) start to measurably improve.

In the semaglutide arm, 86.4% of participants reached ≥5% loss by week 68. About 69% reached ≥10%, 50% reached ≥15%, and 32% reached ≥20%. In the placebo arm, those numbers were 31.5%, 12.0%, 4.9%, and 1.7%.

Even taking the placebo arm into account — which captures the effect of the lifestyle counseling alone — the gap between groups is large at every threshold. The "responder rate" framing is what tells you that the average is not being dragged up by a small number of unusually large responders.

The proportion of participants who lost at least 5% of their body weight at week 68 was 86.4% with semaglutide and 31.5% with placebo… More participants in the semaglutide group than in the placebo group achieved weight reductions of 10% or more, 15% or more, and 20% or more.
Wilding et al., New England Journal of Medicine, 2021

Plain-English read

Reading 86% as "almost everyone responds" is a fair shorthand — but it is not a guarantee that you will. Your own response depends on your physiology, your dose tolerance, how the medication is escalated, and how consistently the protocol is followed. The 5% threshold is meaningful because the health benefits start there — so the goal of any responsible program is to help you hit (and hold) at least that level, not to chase a specific number on the scale. Your clinician will calibrate to what is realistic and clinically valuable for you.

Peer-reviewed source

Once-Weekly Semaglutide in Adults with Overweight or Obesity

Wilding JPH, Batterham RL, Calanna S, et al. · New England Journal of Medicine, 2021 · DOI: 10.1056/NEJMoa2032183

Read the full study on NEJM