Semaglutide for weight loss was tested in large randomized trials, and the headline finding from STEP 1 was a mean body weight reduction of 14.9% over 68 weeks alongside lifestyle intervention. Compounded semaglutide at Telos Rx requires provider approval.
Most articles quote one number and stop. Each pivotal trial was built to answer a different question: how much weight, what happens when treatment stops, whether cardiovascular outcomes change, and whether a swallowed version does the same job.
What the Pivotal Trials Were Designed to Measure
Semaglutide is a GLP-1 receptor agonist made by Novo Nordisk. Its weight management evidence comes from the STEP programme, its cardiovascular evidence from SELECT, and its oral evidence from OASIS 1.
All were randomized, double-blind and placebo-controlled, and all gave both groups a lifestyle intervention. The numbers below describe medication plus diet and activity support, never medication alone.
STEP 1: 68 Weeks in Adults With Obesity
STEP 1 enrolled 1,961 adults with a BMI of 30 or greater, or 27 or greater with at least one weight-related coexisting condition, none of whom had diabetes. Participants were assigned 2 to 1 to once-weekly subcutaneous semaglutide 2.4 mg or placebo for 68 weeks, plus lifestyle intervention.
In the published results, mean body weight change from baseline to week 68 was 14.9% lower in the semaglutide group compared with 2.4% lower on placebo, an estimated treatment difference of 12.4 percentage points. In absolute terms that was 15.3 kg versus 2.6 kg.
Averages hide the spread, so the trial also reported thresholds. Weight reductions of at least 5% were reached by 86.4% of the semaglutide group versus 31.5% on placebo, at least 10% by 69.1% versus 12.0%, and at least 15% by 50.5% versus 4.9%. Roughly half did not reach the 15% threshold, the part usually left out of a headline.
STEP 4: What the Withdrawal Trial Showed
STEP 4 asked a question STEP 1 could not. Every participant took semaglutide for a 20-week run-in, losing a mean of 10.6%. Those who completed it were then randomized either to continue semaglutide or to switch to placebo for the next 48 weeks.
From week 20 to week 68, mean body weight change was a further 7.9% reduction in the group that continued, against a 6.9% increase in the group switched to placebo, a difference of 14.8 percentage points. The trial also reported improvements in waist circumference and systolic blood pressure with continued treatment.
That reframes the rest of the programme: semaglutide was studied as ongoing therapy, not as a course with an endpoint. What happens afterwards is covered in stopping semaglutide and weight regain.
If the evidence looks relevant to your situation, the next step is a written intake reviewed by a licensed provider.
See semaglutide at Telos RxSELECT: Cardiovascular Outcomes, Not Weight
SELECT enrolled 17,604 patients aged 45 or older with preexisting cardiovascular disease and a BMI of 27 or greater, but no history of diabetes. Its primary endpoint was a composite of death from cardiovascular causes, nonfatal myocardial infarction or nonfatal stroke.
Over a mean follow-up of 39.8 months, a primary endpoint event occurred in 6.5% of the semaglutide group versus 8.0% on placebo, a hazard ratio of 0.80. The published trial also recorded adverse events leading to permanent discontinuation in 16.6% of the semaglutide group against 8.2% on placebo.
That result applies to a high-risk population with established cardiovascular disease and does not transfer outside it. Other non-weight findings are in semaglutide benefits beyond weight loss.
OASIS 1: The Oral Form
OASIS 1, published in The Lancet in 2023, tested oral semaglutide 50 mg once daily against placebo for 68 weeks in 667 adults with overweight or obesity and without type 2 diabetes.
Estimated mean body weight change to week 68 was a reduction of 15.1% with oral semaglutide versus 2.4% with placebo. Reductions of at least 5% were reached by 85% versus 26%, at least 10% by 69% versus 12%, and at least 15% by 54% versus 6%. Gastrointestinal adverse events, mostly mild to moderate, were reported by 80% of the oral semaglutide group and 46% of the placebo group.
The Four Trials at a Glance
| Trial | Who was studied | Design | Main reported finding |
|---|---|---|---|
| STEP 1 | 1,961 adults with obesity or overweight plus a related condition, no diabetes | 2.4 mg weekly injection vs placebo, 68 weeks | Mean body weight reduction of 14.9% vs 2.4% |
| STEP 4 | 803 adults who completed a 20-week run-in on semaglutide | Continue vs switch to placebo, weeks 20 to 68 | Further 7.9% reduction vs a 6.9% increase |
| SELECT | 17,604 adults aged 45 plus with established cardiovascular disease, no diabetes | 2.4 mg weekly injection vs placebo, mean 39.8 months | Primary CV events in 6.5% vs 8.0%, hazard ratio 0.80 |
| OASIS 1 | 667 adults with overweight or obesity, no type 2 diabetes | Oral 50 mg daily vs placebo, 68 weeks | Mean body weight reduction of 15.1% vs 2.4% |
Why the Mechanism Explains the Shape of the Data
Semaglutide mimics GLP-1, a hormone released after eating. It acts on appetite and satiety signalling in the brain and slows gastric emptying, so meals feel filling sooner and stay satisfying for longer. It is long-acting, with a half-life of about one week, which is why the injectable form was studied on a once-weekly schedule.
That is why trial weight curves flatten rather than falling indefinitely, and why discontinuation changed the trajectory in STEP 4. The pathway is set out in how GLP-1 works, and the molecule in the complete semaglutide guide.
What the Averages Do Not Tell You
A trial mean describes a studied group under study conditions. It is not a forecast for any individual, and individual results vary. Participants were screened, monitored and supported in ways daily life rarely matches.
Safety belongs alongside efficacy. Semaglutide labels carry a boxed warning about thyroid C-cell tumours seen in rodents, and it is contraindicated with a personal or family history of medullary thyroid carcinoma or MEN 2. Gastrointestinal effects are most common and worst during dose escalation; pancreatitis and gallbladder disease are less common but serious. It is not for use in pregnancy. More detail sits in GLP-1 side effects research.
Trial dosing followed protocol schedules and product labels set their own. Those are reported facts, not instructions: the prescribing provider decides what is appropriate, and pharmacy instructions govern how a preparation is used.
Brand, Compounded and What Telos Rx Provides
The semaglutide family is wider than the three brand names most articles list. FDA-approved products now cover Ozempic in both injectable and oral tablet form, Rybelsus, and Wegovy in both injectable and oral tablet form. Wegovy injection is labelled for weight reduction and cardiovascular risk reduction, also carries an indication in MASH, and includes a higher 7.2 mg option; the Ozempic and Rybelsus labels cover type 2 diabetes. Compounded semaglutide is a separate sixth category, and it sits outside all of those approvals. Compounded semaglutide is not FDA-approved, and it is not a generic. There is no FDA-approved generic semaglutide in the United States, a distinction explained in is there a generic semaglutide.
Compounded semaglutide is prescription-only and is prepared by licensed US compounding pharmacies under federal compounding regulations against a prescription written for an individual patient. Telos Rx covers all 50 states, and the formulation a provider can prescribe may differ depending on where you live.
Telos Rx is LegitScript-certified and operates as an online-first, asynchronous telehealth service, so there is no appointment to book. You complete a written intake and a licensed provider reviews it, often within hours. Approval is subject to evaluation by a licensed provider; approval is not guaranteed. Compounded semaglutide through Telos Rx is a weekly subcutaneous injection.
As of publication, the Telos Rx semaglutide page lists pricing as low as $99 per month, down from $299, with flat pricing that does not rise as a provider titrates the dose, free 48-hour shipping if approved, FSA and HSA acceptance, and the option to cancel anytime. Comparisons sit in the semaglutide cost guide.
Keep Reading
- How to Get Semaglutide
- Where to Buy Semaglutide Online Safely
- Semaglutide Near Me: Online vs Clinic
- How Long Semaglutide Stays in Your System
Frequently Asked Questions
Does semaglutide work for weight loss?
In randomized placebo-controlled trials it produced significantly greater weight reduction than placebo. STEP 1 reported a mean body weight reduction of 14.9% at 68 weeks versus 2.4% on placebo, with both groups receiving lifestyle intervention. Those are group averages in screened trial populations, not predictions for any individual, and results vary from person to person.
How much weight did people lose in the semaglutide trials?
In STEP 1, the mean reduction was 14.9%, or 15.3 kg, over 68 weeks. Thresholds give a better sense of the spread: 86.4% of the semaglutide group reached at least 5% reduction, 69.1% reached at least 10%, and 50.5% reached at least 15%. Roughly half did not reach that highest threshold.
How does semaglutide work?
Semaglutide is a GLP-1 receptor agonist. It mimics a hormone the gut releases after eating, acting on appetite and satiety signalling in the brain and slowing gastric emptying, so meals register as filling sooner and satisfaction lasts longer. The result in trials was reduced energy intake rather than increased energy expenditure.
What happened when people stopped semaglutide in the trials?
STEP 4 tested exactly that. After a 20-week run-in on semaglutide, participants either continued or switched to placebo. From week 20 to week 68, the continuing group had a further 7.9% mean reduction while the placebo group gained 6.9%. Semaglutide was studied as ongoing therapy rather than a fixed course.
Did the trials find benefits other than weight?
SELECT studied 17,604 adults aged 45 or older with established cardiovascular disease and a BMI of 27 or greater but no diabetes. Primary cardiovascular events occurred in 6.5% of the semaglutide group versus 8.0% on placebo, a hazard ratio of 0.80. That finding applies to that high-risk population, not to everyone.
Is compounded semaglutide the same as the medication used in the trials?
No. The trials studied FDA-approved semaglutide products at specified doses. Compounded semaglutide is not FDA-approved and is not a generic; it is prepared by licensed US compounding pharmacies under federal compounding regulations against an individual prescription. Telos Rx is available in all 50 states, though the specific formulation can vary by state, and a licensed provider decides whether it is appropriate.
TelosRX is LegitScript-certified. Compounded medications are not FDA-approved and are prepared under federal compounding regulations. Approval is subject to evaluation by a licensed provider; approval is not guaranteed. Individual results vary. TelosRX operates as an online-first, asynchronous telehealth service.
Want to know whether semaglutide is a reasonable fit for you? Read the semaglutide product page, then complete the written intake: start an online visit. A licensed provider reviews every request, and approval is not guaranteed.