The headline number, and why it is a mean
The figure everyone quotes is about 15% of body weight over 68 weeks, from STEP 1. It is accurate and it is an average, which means roughly half of participants did better and roughly half did worse.
The distribution is the more useful way to read it. In STEP 1, around 86% of participants lost at least 5% of their body weight, about 69% lost at least 10%, about half lost at least 15%, and around a third lost 20% or more. Placebo figures were far lower at every threshold.
The shape of the curve
Weight loss on semaglutide is not linear and expecting it to be is the most common source of unnecessary discouragement.
The curve is shallow during the first weeks, when you are on starting doses that are not therapeutic. It steepens through the escalation and the months after reaching maintenance. It then flattens, with most trial participants approaching a plateau somewhere around the twelve to sixteen month mark.
A plateau is the expected shape of the curve, not a sign the drug has stopped working. The trial curves flatten too.
Over two years
STEP 5 followed participants for 104 weeks and found mean weight loss of about 15% sustained at two years. That is currently the longest randomised evidence available for this drug at the weight-management dose.
Who tends to lose less
- People with type 2 diabetes. In STEP 2, mean loss was closer to 10% on the same dose. This gap is reproducible across the entire drug class and is not a reflection of effort.
- People who do not reach the maintenance dose, whether through tolerability or supply.
- A genuine minority who simply do not respond much. Somewhere around one in ten participants lost less than 5% of body weight.
Early response tends to predict later response
Weight change in the first few months correlates reasonably well with where people end up. Some clinical guidance uses a checkpoint at around three to four months on a therapeutic dose, and a loss of less than about 5% by that point is a reasonable trigger to reassess rather than simply continue.
Reassess is not the same as stop. It might mean a dose change, addressing something else that is in the way, or considering a different agent. It is a conversation, not a verdict.
What changes besides the number on the scale
The trials measured more than weight, and several of the other findings matter more clinically.
- Waist circumference, which tracks visceral fat better than total weight does.
- Systolic blood pressure, which fell meaningfully in the STEP programme.
- Lipids and inflammatory markers including C-reactive protein.
- HbA1c, in people with diabetes or prediabetes.
- And in SELECT, in people with existing cardiovascular disease, a roughly 20% relative reduction in major adverse cardiovascular events over about three years.
The part about lean mass
Some of what comes off is lean tissue. That is true of weight loss generally, not something unique to this drug, but the speed of loss makes it worth attending to.
Resistance training and adequate protein intake are the two mitigations with the most support. People who plan for this from the start do better than people who discover it in month eight.
And if you stop
In the STEP 1 trial extension, participants who came off treatment regained roughly two thirds of the weight they had lost within a year, and most of the cardiometabolic improvements reversed with it.
Expect the result to depend on continuing, because that is what the evidence shows.
Sources
- Wilding JPH, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP 1). N Engl J Med. 2021;384(11):989-1002.
- Davies M, et al. Semaglutide 2.4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2). Lancet. 2021;397(10278):971-984.
- Garvey WT, et al. Two-year effects of semaglutide in adults with overweight or obesity: the STEP 5 trial. Nat Med. 2022;28(10):2083-2091.
- Wilding JPH, et al. Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension. Diabetes Obes Metab. 2022;24(8):1553-1564.
- Lincoff AM, et al. Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes (SELECT). N Engl J Med. 2023;389(24):2221-2232.
- Wegovy (semaglutide) injection, prescribing information. Novo Nordisk.