Semaglutide Results: What the Clinical Data Actually Shows
Dose-response data, week-by-week weight loss timeline, responder rates, and metabolic outcomes from 1961 participants in TRIUMPH-1 — published New England Journal of Medicine, 2021.
TRIUMPH-1 Key Findings at a Glance
Source: New England Journal of Medicine, 2021 — DOI: 10.1056/NEJMoa2032183
How Much Weight Loss at Each Dose?
TRIUMPH-1 tested six dose arms over 48 weeks. The dose-response relationship was clear: higher doses produced greater weight loss at every level above placebo.
| Dose | Mean Weight Loss at 48 Weeks | Example: 250 lb person | Example: 200 lb person |
|---|---|---|---|
| Standard dose | 14.9% | ~37.3 lbs | ~29.8 lbs |
Figures represent mean percent change in body weight. Individual results vary. Source: TRIUMPH-1, NEJM 2023.
What 24% Weight Loss Means in Practice
A 24.2% reduction sounds abstract. Here is what it translates to at different starting weights:
Based on 24.2% mean weight loss at 24mg over 48 weeks from TRIUMPH-1. These are statistical means — outcomes vary individually.
Who Responds — and How Well?
Average results tell part of the story. The responder breakdown from the 24mg arm of TRIUMPH-1 shows just how few participants saw poor results:
TRIUMPH-1, 24mg arm. Participants: BMI 30–50, no type 2 diabetes, no prior GLP-1 use within 6 months.
Beyond Weight Loss: Metabolic Improvements
Semaglutide's triple receptor mechanism produces metabolic benefits beyond the scale. TRIUMPH-1 reported these additional outcomes at 48 weeks (24mg arm):
| Metabolic Marker | Change | Clinical Significance |
|---|---|---|
| Triglycerides | -22% | Significant reduction in cardiovascular risk marker |
| Systolic Blood Pressure | -6.2 mmHg | Clinically meaningful BP reduction |
| Fasting Glucose | -7.6% | Improved insulin sensitivity and glucose regulation |
| Lean Mass | ~-3.5% | Small reduction — mitigated by resistance training |
Retatrutide vs Tirzepatide vs Semaglutide: Trial Outcomes
| Metric | Retatrutide | Tirzepatide | Semaglutide |
|---|---|---|---|
| Drug class | GIP/GLP-1/Glucagon triple | GIP/GLP-1 dual | GLP-1 single |
| Max dose (studied) | 24mg weekly | 15mg weekly | 2.4mg weekly |
| Peak weight loss (mean) | 24.2% | 22.5% | 15.0% |
| Trial duration | 48 weeks (Ph2) | 72 weeks (Ph3) | 68 weeks (Ph3) |
| Trial size | 338 participants | 2,539 participants | 1,961 participants |
| FDA approval (obesity) | Not approved | Approved (Zepbound, 2023) | Approved (Wegovy, 2021) |
| Thermogenesis effect | Yes — glucagon-driven | Minimal | Minimal |
Sources: TRIUMPH-1 (NEJM 2023), SURMOUNT-1 (NEJM 2022), STEP-1 (NEJM 2021).
What Happens When You Stop Taking Semaglutide?
Weight regain after stopping Semaglutide is expected. TRIUMPH-1 included a 24-week follow-up period after the active treatment phase. Participants regained a portion of lost weight as the drug's appetite-suppressing and thermogenic effects diminished.
Frequently Asked Questions
How much weight can you lose on Semaglutide?
In TRIUMPH-1 (N=1961, 68 weeks), participants on the highest 24mg dose lost a mean of 24.2% of body weight. At 12mg: 22.8%. At 8mg: 17.3%. For a 250-pound person, 24.2% equals roughly 60.5 pounds. These are mean outcomes — 91% of participants on the highest dose lost more than 15% of body weight, and 75% lost more than 20%.
Does Semaglutide cause muscle loss?
TRIUMPH-1 reported approximately 3.5% lean mass reduction alongside total weight loss. This is common with rapid weight loss. Fat mass decreased proportionally much more, making the loss fat-preferential. Resistance training 2–3 times per week combined with high protein intake (targeting 1g per pound of bodyweight) substantially reduces lean mass loss during treatment.
What happens when you stop Semaglutide?
TRIUMPH-1 tracked participants for 24 weeks post-treatment. Weight regain is common after stopping any GLP-class drug. The hormonal suppression of appetite diminishes, and hunger signals return toward baseline. Most participants regain a portion of lost weight without continued treatment. This mirrors what occurs with tirzepatide and semaglutide discontinuation.
Who responds best to Semaglutide?
TRIUMPH-1 enrolled adults with BMI 30–50 without type 2 diabetes who had not used GLP-1 drugs within the prior 6 months. Within this population, the highest-dose group showed the strongest results. People with insulin resistance, elevated triglycerides, and higher baseline BMI tended toward greater absolute weight reduction.
How does Semaglutide compare to Ozempic for weight loss?
Wegovy (semaglutide 2.4mg) achieved approximately 15% mean weight loss in the STEP-1 trial (68 weeks). TRIUMPH-1 showed Semaglutide at 24mg achieving 24.2% mean weight loss in 48 weeks. The additional ~9 percentage points appear attributable to the glucagon receptor component, which drives thermogenesis beyond what GLP-1 alone achieves. However, semaglutide is FDA approved and available; retatrutide remains investigational.
References & Sources
- [1]Wilding JPH, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP 1). N Engl J Med. 2021;384:989–1002.
- [2]Lincoff AM, et al. Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes (SELECT). N Engl J Med. 2023;389:2221–2232.
- [3]FDA — Semaglutide (Wegovy) Approval and Drug Label
- [4]PubMed search: semaglutide obesity clinical trials
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