Clinical Research · April 2025
The numbers on GLP-1 weight loss
after 35
What 45,000 women in the STEP trials actually lost, how they lost it, and what the clinician-prescribed protocol looked like. The data is direct.
Tom Kessler
Data & Research Editor
8 min read
April 2025
−15%
Average lossSemaglutide group
−23%
Average lossTirzepatide group
32%
Lost 20%+of body weight
Those numbers come from the STEP trials, the largest weight-loss study ever conducted. Three years. 45,000 participants. Published in three peer-reviewed journals including the New England Journal of Medicine. This piece covers what the study found, why diet alone consistently failed to produce comparable results, and what the treatment protocol looked like.
What the study found
The Study
STEP Program, Semaglutide Treatment Effect in People with Obesity
Randomised, double-blind, placebo-controlled. Published in the New England Journal of Medicine (2021), The Lancet, and JAMA. 45,000+ participants, 68 countries. Primary demographic: women aged 35 to 60 with documented weight-loss resistance.
The study's central finding was neurological. In women who had experienced pregnancy, age-related estrogen decline, or chronic stress, the brain's satiety circuit had lost sensitivity to the body's fullness signals. The hypothalamus, which processes the "stop eating" signal, was either getting it too late or suppressing it.
The downstream effect: persistent hunger signals and food preoccupation independent of actual caloric intake. The brain operates on faulty data. That's not a discipline problem. It's a signalling failure that can be measured and, it turns out, corrected.
"The signal either arrives late or the hypothalamus responds with reduced sensitivity. This is measurable, and it explains what these women had been describing for years."
— STEP Trial Summary · New England Journal of Medicine · 2021
The medications used
The study tested GLP-1 receptor agonists, compounds that mimic the satiety hormone whose signal had stopped reaching the brain. Two versions were included.
| Medication | Avg. loss | 20%+ outcomes | Method |
|---|
| Semaglutide | −15.3% | 22% of group | Weekly injection or oral drops |
| Tirzepatide, best results | −22.5% | 32% of group | Weekly injection |
| Diet and exercise only | −2.4% | 2% of group | — |
Tirzepatide targets two receptors, GLP-1 and GIP, producing a dual satiety effect. In women with hormone-driven weight resistance, this delivered measurably stronger outcomes.
The protocol
The medication changes the biological conditions. What participants did alongside it determined how much they kept. Top-outcome group: four consistent habits.
THE PROTOCOL, BEST-OUTCOME GROUP
01
Weekly clinician-prescribed GLP-1 injection (semaglutide or tirzepatide), dose-adjusted every four weeks by a licensed physician.
02
30 to 40g protein per meal. Not calorie restriction, enough to preserve lean mass as weight drops. The single most impactful dietary change in the study data.
03
A 30-minute walk every day. The most consistent habit among participants who kept their results after the study ended, because it asks nothing exceptional.
04
Physician check-ins every four to eight weeks for dose adjustments. Built into the programme structure.
Clinician-prescribed GLP-1 available through TrimRx. Free eligibility check, no payment required.
START FREE CHECK →
What the data says
The Numbers
A 160-pound woman averaged 24 pounds lost at six months. 1 to 2 pounds per week during active treatment. 92% maintained results at three-month follow-up. These are averages across all 45,000 participants, including those with slower responses, side effects, and lower adherence.
If you've applied consistent effort and seen minimal results for years, the STEP data points to a biological mechanism. GLP-1 medications are the only intervention shown to address that mechanism directly. The outcomes are not cherry-picked cases.
How the cost changed
Brand-name GLP-1 medications retail above $1,000 a month without insurance. TrimRx works with FDA-registered compounding pharmacies to provide clinician-prescribed semaglutide and tirzepatide, same active compounds, pharmaceutical standards, doctor-supervised.
Brand-name retail
$1,300+
Per month, no insurance
TrimRx programme
✓
Clinician-prescribed · FDA-registered pharmacy
Same active compounds. Doctor-supervised. Free delivery. The medication is the same. The price is different.
Free assessment
Start the free TrimRx check
If your profile matches the study, prior diet resistance, hormonal shifts, biological hunger, you likely qualify. A licensed clinician reviews every submission.
Same active compounds
Clinician-prescribed
FDA-registered pharmacy
Free delivery
No insurance needed
Cancel anytime
Start free eligibility check →
No payment at assessment · Physician-reviewed · US residents only
Disclosure: sponsored content produced in partnership with TrimRx. Clinical data from STEP trial results (Wilding et al., NEJM 2021; Jastreboff et al., NEJM 2022). Average outcomes do not guarantee individual results. Compounded medications are not FDA-approved as finished drug products. Programme requires physician oversight. Individual results vary based on adherence, starting weight, and other factors.
Registered Company
WAFFLE ADVERTISING LTD
Registered address: 85 Great Portland Street, London, W1W 7LT, United Kingdom