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How Much Weight People Lost on Semaglutide in the Trials

STEP 1 put the mean at −14.9% over 68 weeks. Half the participants reached 15%, about one in three never reached 10%, and STEP 4 showed the weight coming back when the drug stopped.

Owen Castellanos8 min read
What STEP 1 participants reached at 68 weeksSemaglutide 2.4 mg above, placebo below, in each pairLost 5% of body weight or more86.4%31.5%Lost 10% or more69.1%12%Lost 15% or more50.5%4.9%1,961 adults without diabetes, 68 weeks, lifestyle support in both arms.Mean change was minus 14.9% against minus 2.4%.

The figure that sells semaglutide is roughly fifteen percent. It came out of one trial, it is a mean rather than a promise, and the spread beneath it is wide enough that two people quoting the same number can be describing very different years. Before weighing what sellers charge on the semaglutide board, it is worth knowing what that number was measured on.

STEP 1, where the headline comes from

STEP 1 randomized 1,961 adults with a body-mass index of 30 or higher, or 27 or higher with one weight-related condition, and without diabetes. They received once-weekly semaglutide 2.4 mg or placebo for 68 weeks. Both arms also received a lifestyle intervention.[1]

Mean change in body weight was −14.9% against −2.4% on placebo, an estimated treatment difference of −12.4 percentage points (95% CI, −13.4 to −11.5). In kilograms that was −15.3 kg against −2.6 kg.[1]

The average conceals a wide spread

A mean is a poor guide to a personal outcome, and STEP 1 published the distribution alongside it. Weight reductions of 5% or more were reached by 86.4% of the semaglutide group against 31.5% on placebo; 10% or more by 69.1% against 12.0%; and 15% or more by 50.5% against 4.9%.[1]

Read the other way, that means about one participant in three did not reach 10% even on the drug, and roughly half did not reach 15%. Those people took the same injections for the same 68 weeks and paid the same bill. Nothing in the trial predicts in advance which group anyone lands in, which is a reason to read how the side effects behave before assuming a long course is affordable in practice.

The comparator arm was doing real work

Placebo in STEP 1 was not nothing. Both arms received the same lifestyle intervention, and the placebo group lost 2.4% of body weight, with 31.5% of them reaching a reduction of 5% or more.[1] That is the benchmark the drug was measured against.

The consequence is easy to miss when a seller bundles coaching, a food diary and check-ins into a monthly fee. The treatment difference of 12.4 percentage points is what semaglutide added on top of diet and activity support, not the combined effect of drug and program. A plan that charges a premium for the counseling layer is charging for something already present on both sides of the trial.

STEP 4 shows the drug was still working at the end

STEP 4 was built as a withdrawal trial. Participants took semaglutide for a 20-week run-in, losing a mean of 10.6%, and 803 of them who had reached the 2.4 mg maintenance dose were then randomized to continue or to switch to placebo for another 48 weeks.[2]

From week 20 to week 68, the group that continued lost a further 7.9%. The group switched to placebo regained 6.9% — a difference of −14.8 percentage points (95% CI, −16.0 to −13.5). Waist circumference and systolic blood pressure moved the same way.[2]

Two things follow. Weight was still falling at the point most trials stop, so the 68-week figure is not a ceiling. And the effect is a treatment effect, not a cure: it reverses on withdrawal, which is the subject of the stopping article and the single largest cost consideration on this site.

With type 2 diabetes the figure is smaller

STEP 2 ran the same dose for the same 68 weeks in 1,210 adults with overweight or obesity and type 2 diabetes. Estimated change in body weight was −9.6% with semaglutide 2.4 mg against −3.4% with placebo, a treatment difference of −6.2 percentage points (95% CI, −7.3 to −5.2).[3]

That is roughly a third less than the non-diabetes result, from the same molecule at the same dose. A seller quoting 15% to a buyer with diabetes is quoting the wrong trial.

The 5% threshold is worth keeping in view here, because that is the point at which weight loss is generally treated as clinically meaningful rather than cosmetic. In STEP 2 it was reached by 68.8% of the semaglutide 2.4 mg group against 28.5% on placebo, an odds ratio of 4.88 (95% CI, 3.58 to 6.64).[3] A smaller mean can still carry a large share of people past a threshold that matters.

Against the older weekly-versus-daily comparison

STEP 8 randomized 338 adults without diabetes to semaglutide 2.4 mg weekly or liraglutide 3.0 mg daily. Mean weight change was −15.8% with semaglutide against −6.4% with liraglutide, a difference of −9.4 percentage points (95% CI, −12.0 to −6.8).[4]

Tolerability separated the two as much as potency did. Treatment was discontinued for any reason by 13.5% on semaglutide and 27.6% on liraglutide, while gastrointestinal events were reported at similar rates in both arms.[4] For how semaglutide sits against the other molecule sold alongside it, see the molecule comparison.

What these numbers are not

Every figure above came from a trial of the branded, FDA-approved product at its labeled dose, with dose escalation supervised and a lifestyle program running in both arms. Most sellers listed on the review index supply compounded preparations, which are made to order against a prescription and are not reviewed by the FDA for safety, efficacy or quality before dispensing. The trials describe the molecule, not the vial.

The other practical gap is the dose. The 14.9% figure belongs to 2.4 mg weekly, reached after 16 weeks of escalation. A plan that caps below that dose is not selling the protocol the trial ran. Neither is one whose monthly price climbs as the dose climbs, which is why the per-dose pricing on the flat-dose board changes the arithmetic more than the headline percentage does.

Frequently asked

How much weight do people lose on semaglutide?
In STEP 1, the mean change over 68 weeks was −14.9% against −2.4% on placebo, in 1,961 adults without diabetes. The distribution matters more than the mean: 69.1% reached 10% or more and 50.5% reached 15% or more, so roughly one participant in three did not reach 10%.
Is the result different for people with type 2 diabetes?
Yes, and by a wide margin. STEP 2 ran the same 2.4 mg dose for the same 68 weeks in 1,210 adults with type 2 diabetes and found −9.6% against −3.4% with placebo. That is about a third less than the non-diabetes figure from the same molecule.
How long does it take to reach the full effect?
Longer than 68 weeks, on the evidence available. STEP 4 continued treatment past a 20-week run-in and the group that stayed on the drug lost a further 7.9% between week 20 and week 68. Weight was still falling when the trial ended.
What happens to the weight if treatment stops?
It returns. In STEP 4, participants switched to placebo at week 20 regained 6.9% by week 68, while those who continued lost a further 7.9%. The difference between the two arms was 14.8 percentage points over 48 weeks.

Sources

  1. [1] Wilding JPH, Batterham RL, Calanna S, et al. (2021). Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. PMID 33567185
  2. [2] Rubino D, Abrahamsson N, Davies M, et al. (2021). Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity: The STEP 4 Randomized Clinical Trial. JAMA. PMID 33755728
  3. [3] Davies M, Færch L, Jeppesen OK, et al. (2021). Semaglutide 2·4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2): a randomised, double-blind, double-dummy, placebo-controlled, phase 3 trial. Lancet. PMID 33667417
  4. [4] Rubino DM, Greenway FL, Khalid U, et al. (2022). Effect of Weekly Subcutaneous Semaglutide vs Daily Liraglutide on Body Weight in Adults With Overweight or Obesity Without Diabetes: The STEP 8 Randomized Clinical Trial. JAMA. PMID 35015037

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