# Weight Loss Clinical Trials in Adults and Comparison Data

> Weight Trials and Comparisons in Semaglutide New Mexico — Read the semaglutide New Mexico breakdown of STEP 1, STEP 5, STEP TEENS, oral SNAC bioavailability, and the SURMOUNT-5 head-to-head tirzepatide comparison.

**Part Two · Weight Cohorts, Oral Delivery & Head-to-Head Trials**

Reviewing the 68-week STEP 1 cohort, the 104-week STEP 5 durability study, adolescent outcomes in STEP TEENS, oral SNAC pharmacokinetics, and the 2025 SURMOUNT-5 comparison against tirzepatide.

## Key Findings From Weight and Comparative Trials

- In STEP 1 (2021, n = 1,961), once-weekly 2.4 mg subcutaneous semaglutide produced a -14.9% mean body-weight change at week 68 versus -2.4% with placebo (~12.4 percentage-point difference).
- In STEP 5 (2022), continuous once-weekly 2.4 mg dosing over 104 weeks maintained clinically meaningful weight reduction versus placebo.
- In STEP TEENS (2022), once-weekly 2.4 mg over 68 weeks significantly reduced BMI compared with placebo in adolescents with obesity.
- In SURMOUNT-5 (2025, n = 751), tirzepatide produced a -20.2% mean weight reduction at week 72 compared with -13.7% on semaglutide 2.4 mg (~6.5 percentage-point difference, P less than 0.001).

## What STEP 1, STEP 5, and STEP TEENS Measured at 2.4 mg Weekly

Once-weekly 2.4 mg subcutaneous semaglutide was evaluated across 68-week adult, 104-week adult, and 68-week adolescent weight-management cohorts, beginning with the 2021 [once-weekly STEP 1 obesity study](https://pubmed.ncbi.nlm.nih.gov/33567185/) led by Wilding and colleagues. That trial randomized 1,961 adults with overweight or obesity without diabetes to 2.4 mg weekly or placebo. After 68 weeks, participants in the active arm achieved a mean body-weight change of -14.9% compared with -2.4% in the placebo group, representing an estimated treatment difference of about 12.4 percentage points.

Garvey and colleagues reported two-year outcomes in the 2022 [two-year STEP 5 trial](https://pubmed.ncbi.nlm.nih.gov/36216945/). Across 104 weeks of continuous once-weekly 2.4 mg subcutaneous dosing in adults with overweight or obesity, the trial confirmed sustained, clinically meaningful weight loss compared with placebo.

That same year, Weghuber and the STEP TEENS investigators published their 68-week [adolescent obesity trial](https://pubmed.ncbi.nlm.nih.gov/36322838/) in the New England Journal of Medicine. Adolescents with obesity assigned to once-weekly 2.4 mg subcutaneous dosing achieved a significantly greater reduction in body mass index than peers receiving placebo. Reading these three trials together shows how the 2.4 mg weekly regimen performed across 68-week adult, 104-week adult, and 68-week adolescent cohorts.

- **-14.9%** — Mean body-weight change at week 68 in STEP 1 vs -2.4% placebo
- **12.4** — Approximate percentage-point advantage over placebo in STEP 1
- **104** — Weeks of follow-up demonstrating sustained weight reduction in STEP 5
- **-20.2%** — Tirzepatide weight change vs -13.7% on semaglutide in SURMOUNT-5

## Oral SNAC Bioavailability and the 2025 SURMOUNT-5 Trial Against Tirzepatide

As detailed in the 2024 [StatPearls clinical pharmacology summary](https://www.ncbi.nlm.nih.gov/books/NBK603723/), oral bioavailability of semaglutide with SNAC is approximately 0.4-1%. Both oral and subcutaneous semaglutide have an elimination half-life of approximately 1 week and remain in circulation for approximately 5 weeks after the last dose.

In 2025, Aronne and the SURMOUNT-5 investigators published their 72-week [head-to-head trial against tirzepatide](https://pubmed.ncbi.nlm.nih.gov/40353578/) comparing once-weekly semaglutide 2.4 mg with tirzepatide in 751 adults with obesity. At week 72, mean body-weight change was -20.2% with tirzepatide versus -13.7% with semaglutide 2.4 mg, an approximate 6.5 percentage-point advantage for tirzepatide (P<0.001). When I place SURMOUNT-5 beside the STEP cohorts, I see how a head-to-head trial in 751 participants answers comparative efficacy questions far more directly than cross-trial estimates.

| Trial & Year | Cohort & Duration | Regimen Tested | Key Reported Finding |
| --- | --- | --- | --- |
| STEP 1 (2021) | 1,961 adults without diabetes · 68 weeks | Semaglutide 2.4 mg weekly vs placebo | -14.9% vs -2.4% mean weight change (~12.4 percentage-point difference) |
| STEP 5 (2022) | Adults with overweight or obesity · 104 weeks | Semaglutide 2.4 mg weekly vs placebo | Sustained, clinically meaningful two-year weight loss vs placebo |
| STEP TEENS (2022) | Adolescents with obesity · 68 weeks | Semaglutide 2.4 mg weekly vs placebo | Significantly greater BMI reduction than placebo |
| SURMOUNT-5 (2025) | 751 adults with obesity · 72 weeks | Tirzepatide vs semaglutide 2.4 mg weekly | -20.2% vs -13.7% mean weight change (~6.5 percentage-point tirzepatide advantage, P < 0.001) |

![Tall glass of clear water beside a stoneware saucer and single white tablet at sunrise](images/fasting-water-glass-morning.webp)

*Oral bioavailability of semaglutide with SNAC is approximately 0.4-1%, and both oral and subcutaneous routes have an elimination half-life of approximately 1 week (~5 weeks in circulation after the last dose).*

## How prescription access relates to the weight trials

After comparing the weight trials, I turn to how the medicines reach patients. FDA-approved semaglutide products require a prescription. Individually compounded medicines also depend on a prescription, though FDA approval does not cover the compounded preparation. Research-labelled material is intended for laboratory work. Semaglutide care at Promise Peptides (mypromise.com) is prescription-only, with a clinician assessing the patient and making the prescribing decision.

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On Semaglutide New Mexico, I share my own notes on published research for educational reading only, offering no medical advice, clinical care, or treatment instructions.