GLP-1 efficacy: what the registration trials actually show
Wegovy at 14.9% mean weight loss. Zepbound at 22.5%. Saxenda at 7.4%. The numbers behind every weight-loss program's marketing copy, and what they hide.
TLDR. Mean weight loss at 68 to 72 weeks in the FDA registration trials: Zepbound 15 mg at 22.5 percent (SURMOUNT-1, NEJM 2022), Wegovy 2.4 mg at 14.9 percent (STEP-1, NEJM 2021), Saxenda at 7.4 percent (SCALE), Qsymia at 10.9 percent (EQUIP), Contrave at 6.1 percent (COR-1), placebo at 2.4 percent. Of Zepbound 15 mg patients, 91 percent achieved at least 5 percent weight loss and 57 percent achieved at least 15 percent. Numbers are intent-to-treat and include patients who dropped out. Real-world adherence drops the average meaningfully.
| Fact | Value | Source | Verified |
|---|---|---|---|
| Zepbound 15 mg mean weight loss | 22.5% at 72 weeks | SURMOUNT-1, NEJM 2022 | May 2026 |
| Wegovy 2.4 mg mean weight loss | 14.9% at 68 weeks | STEP-1, NEJM 2021 | May 2026 |
| Saxenda 3.0 mg mean weight loss | 7.4% | SCALE, NEJM 2015 | May 2026 |
| Qsymia mean weight loss | 10.9% | EQUIP, Obesity 2012 | May 2026 |
| Contrave mean weight loss | 6.1% | COR-1, Lancet 2010 | May 2026 |
| Placebo mean weight loss | 2.4% (STEP-1) | STEP-1, NEJM 2021 | May 2026 |
Every weight-loss program in the chart cites efficacy. Some quote registration trial averages ("17% body weight reduction!"). Some quote internal program data ("our patients lose 14% in 12 months"). Some quote Reddit testimonials. The numbers vary by 2-3x depending on which source you pick.
This post puts the actual peer-reviewed registration trial numbers next to each other so you can read program marketing through them.
The headline numbers
From FDA registration trials, mean percentage weight loss at 68 weeks (~16 months) of treatment, intent-to-treat:
| Drug | Trial | Mean weight loss | ≥5% weight loss | ≥15% weight loss |
|---|---|---|---|---|
| Tirzepatide 15mg (Zepbound) | SURMOUNT-1 | 22.5% | 91% | 57% |
| Tirzepatide 10mg | SURMOUNT-1 | 21.4% | 89% | 50% |
| Tirzepatide 5mg | SURMOUNT-1 | 16.0% | 85% | 34% |
| Semaglutide 2.4mg (Wegovy) | STEP-1 | 14.9% | 86% | 32% |
| Liraglutide 3.0mg (Saxenda) | SCALE | 7.4% | 63% | 14% |
| Naltrexone-bupropion (Contrave) | COR-1 | 6.1% | 53% | 12% |
| Phentermine-topiramate (Qsymia) | EQUIP | 10.9% | 67% | 32% |
| Placebo | STEP-1 | 2.4% | 32% | 2% |
Sources: SURMOUNT-1 (NEJM 2022), STEP-1 (NEJM 2021), SCALE (NEJM 2015), COR-1 (Lancet 2010), EQUIP (Obesity 2012).
What the headline numbers hide
Adherence drops over time. The 14.9% Wegovy number is intent-to-treat, it includes patients who dropped out and were imputed at their baseline weight. Among patients who actually completed 68 weeks of treatment ("on-treatment"), Wegovy averages 17.4% weight loss. Programs sometimes quote on-treatment numbers as if they're representative, when ITT is the right comparison for cash-pay shoppers deciding whether to start.
Maintenance ≠ active titration. Most weight loss happens in the first 9-12 months as patients titrate up. After that, weight typically stabilizes. If a program says "17% weight loss in our patients" without specifying the timeframe, they're probably citing year-one averages.
Weight regain after stopping is real. The STEP-4 extension trial showed patients who stopped semaglutide regained ~two-thirds of lost weight within 12 months. The medication is a weight management tool while taken; it is not a cure that persists after discontinuation.
Side-effect-driven discontinuation removes the worst non-responders. About 7% of Wegovy patients and 5% of Zepbound patients discontinue due to GI side effects in the first 16 weeks. Those patients tend to be the ones who would have responded least anyway. That subtly inflates the average for who remains.
How program-reported outcomes compare
Programs that publish their own outcomes data tend to report numbers in line with or modestly below registration trials. Two examples:
- Form Health publishes 16% mean weight loss at 12 months. This is roughly consistent with Wegovy's 14.9% ITT (most Form patients are on Wegovy or Zepbound) but with a self-selected adherent population.
- Calibrate publishes 14.7% at 12 months for their cohort. Similar.
What you should be skeptical of: programs that claim outcomes meaningfully above registration trials (e.g., "20% in 6 months on semaglutide") without naming a tirzepatide subset. The math doesn't work.
Side effects in the trials
From STEP-1 and SURMOUNT-1, % of patients reporting each side effect at any point during the trial:
| Side effect | Wegovy 2.4mg | Zepbound 15mg | Placebo |
|---|---|---|---|
| Nausea | 44.2% | 29.0% | 16.1% |
| Diarrhea | 31.5% | 23.0% | 15.9% |
| Constipation | 23.4% | 17.1% | 9.5% |
| Vomiting | 24.8% | 12.2% | 6.4% |
| Discontinuation due to AE | 7.0% | 4.3% | 3.0% |
Side effects are common but mostly mild-to-moderate, peak in the titration phase and subside as patients reach maintenance dose. Microdose protocols (e.g., Noom Med's offering) start at fractions of the standard 0.25mg starting dose and may reduce side-effect intensity, though no head-to-head trials yet exist.
What this means for your program choice
Three things follow from the trial data.
1. The drug matters more than the program. Whichever program you choose, your weight loss outcome is mostly determined by which medication you receive and at what dose. Tirzepatide outperforms semaglutide outperforms liraglutide. A program that gets you on tirzepatide at maintenance dose will beat a program that keeps you on semaglutide 1.0mg.
2. Adherence matters second. Programs that improve adherence (through behavioral coaching, regular clinician check-ins or just dose continuity through supply gaps) probably beat programs that just dispense.
3. Set a 12-month time horizon. If you start expecting 14-22% weight loss in 3 months, you'll be disappointed. Most weight loss happens between months 3 and 12.
The published trial numbers are the realistic ceiling. Most patients land 60-90% of the trial mean, and that's still life-changing for most starting populations. Our methodology weighs program quality against this realistic outcome distribution rather than against marketing copy.
Frequently asked questions
Which GLP-1 produces the most weight loss in registration trials?
Tirzepatide 15 mg (Zepbound) at 22.5 percent mean weight loss in SURMOUNT-1, published in NEJM 2022 at 72 weeks. Semaglutide 2.4 mg (Wegovy) at 14.9 percent in STEP-1, NEJM 2021 at 68 weeks. The clinically relevant equivalence point is Wegovy 2.4 mg versus Zepbound 5 mg, both producing roughly 16 percent at the registration-trial dose.
Do the trial numbers match what real-world patients lose?
Real-world averages run lower because adherence drops over time. The 14.9 percent Wegovy number is intent-to-treat. That means it includes patients who dropped out and were imputed at baseline. Among patients who stayed on the maximum dose through 68 weeks, average weight loss was closer to 17 to 18 percent. Real-world cohorts at 12 months typically average 10 to 14 percent.
What percentage of patients hit at least 5 percent weight loss?
From STEP-1 and SURMOUNT-1: 86 percent of Wegovy 2.4 mg patients, 91 percent of Zepbound 15 mg patients, 89 percent of Zepbound 10 mg patients, 85 percent of Zepbound 5 mg patients. The 5 percent threshold matters because it is the FDA-recognized clinical-benefit floor for obesity medications.
How does Saxenda or Contrave compare to Wegovy?
Much lower efficacy. Saxenda (liraglutide 3.0 mg) hit 7.4 percent in SCALE, roughly half of Wegovy. Contrave (naltrexone-bupropion) hit 6.1 percent in COR-1. Qsymia (phentermine-topiramate) hit 10.9 percent in EQUIP. The order is Zepbound > Wegovy > Qsymia > Saxenda > Contrave on mean weight loss.
Are the trial numbers a good prediction for me personally?
They are a mean across thousands of patients. Your personal trajectory may be higher or lower depending on adherence, lifestyle change, starting BMI, and individual response. Most patients fall within 5 percentage points of the trial mean either way; outliers are real and a 5 percent responder is not a treatment failure if you stick with the medication.
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