Semaglutide Clinical Trial Results, Summarized

Semaglutide is one of the most studied weight-loss medicines ever. Since 2021, its maker has run a long series of large randomized trials, mostly under the name STEP (Semaglutide Treatment Effect in People with obesity), plus a heart outcomes trial called SELECT, a higher-dose trial called STEP UP and pill trials called OASIS. Headlines usually quote one number from one of them, often “15% weight loss,” without saying who was studied, for how long, or what happened when people stopped.

This guide summarizes the main trials in plain English: who took part, what they were given, the average results, the side effects, and the limits of each study. It is meant to help you read the evidence and ask better questions, not to tell you which medicine or dose to use.

Educational only. This is not medical advice. Trial results are averages from carefully selected volunteers and do not predict what will happen to any one person. Semaglutide is a prescription medicine; decisions about whether to start it, which form or dose to use, and when to change or stop it belong to you and your prescriber.

The short answer

In the main weight-loss trials, adults without diabetes who took weekly semaglutide 2.4 mg (sold as Wegovy) with lifestyle counseling lost about 15% to 16% of their body weight on average over 68 weeks, compared with about 2% to 6% on placebo. In STEP 1, the biggest of these trials, the average was 14.9% versus 2.4%, and about half of people on semaglutide lost at least 15% of their starting weight.

A few other results matter just as much:

• People with type 2 diabetes lost less: 9.6% versus 3.4% in STEP 2.
• Weight loss held for two years on treatment (15.2% at week 104 in STEP 5), but most of it came back within a year of stopping (STEP 4 and the STEP 1 extension).
• SELECT found a 20% lower risk of heart attack, stroke or cardiovascular death in adults with existing heart or blood vessel disease and excess weight.
• A higher 7.2 mg dose averaged 18.7% in STEP UP, and a daily 25 mg pill averaged 13.6% in OASIS 4.
• Digestive side effects such as nausea, diarrhea, vomiting and constipation were the most common problem in every trial.

If you are new to the medicine itself, start with What Is Semaglutide? and then come back here for the details.

How to read these trials

A few features are shared by almost every trial below, and knowing them makes the numbers much easier to interpret.

• Everyone got lifestyle support, including the placebo group. Participants in both arms were usually counseled to follow a reduced-calorie diet and to be more physically active. So the placebo result shows roughly what diet and activity counseling alone achieved in that trial, and the difference between the two arms is the extra effect of the medicine.
• Results are a percentage of starting weight. A 15% loss for someone who starts at 230 pounds is about 35 pounds. Most participants had a body mass index (BMI) of 30 or more, or 27 or more with a weight-related condition such as high blood pressure, and average starting weights were around 100 to 113 kg (about 220 to 250 pounds).
• The dose went up slowly. In the STEP trials, semaglutide started low and was raised over about 16 weeks to the full weekly dose, which is one reason side effects were most common early on.
• “Treatment policy” versus “on treatment.” Trials often report two versions of the result. The main one counts everyone who was randomized, including people who stopped the drug. A second one estimates what happened if everyone had kept taking it, and it is usually a little larger. In STEP 2, for example, the first version was 9.6% and the second was 10.6%. Company press releases and social media posts sometimes quote the larger number, so check which one you are looking at. This guide uses the main (treatment policy) result unless it says otherwise.
• Most were funded by Novo Nordisk, which makes semaglutide. They were still randomized, mostly double-blind and published in major peer-reviewed journals, but it is worth knowing who paid.
• Volunteers are not average patients. In several STEP trials, about three-quarters or more of participants were women, and trial participants get more contact with staff than most people do in everyday care. Real-world results are often somewhat smaller.

The main trials at a glance

Trial	Who took part	Length	Semaglutide result	Placebo or comparison
STEP 1	1,961 adults without diabetes	68 weeks	−14.9% (2.4 mg weekly)	−2.4%
STEP 2	1,210 adults with type 2 diabetes	68 weeks	−9.6% (2.4 mg); −7.0% (1.0 mg)	−3.4%
STEP 3	611 adults without diabetes, intensive behavioral therapy	68 weeks	−16.0%	−5.7%
STEP 4	803 adults who had already lost 10.6% in 20 weeks	48 more weeks	−7.9% more (kept taking it)	+6.9% (switched to placebo)
STEP 5	304 adults without diabetes	104 weeks	−15.2%	−2.6%
STEP 8	338 adults without diabetes	68 weeks	−15.8%	−6.4% (liraglutide 3.0 mg); −1.9% (placebo)
STEP TEENS	201 adolescents aged 12 to 17	68 weeks	BMI −16.1%	BMI +0.6%
STEP UP	1,407 adults without diabetes, BMI 30+	72 weeks	−18.7% (7.2 mg); −15.6% (2.4 mg)	−3.9%
OASIS 4	307 adults without diabetes	64 weeks	−13.6% (25 mg pill daily)	−2.2%
SELECT	17,604 adults with heart or blood vessel disease, no diabetes	Median about 3.5 years	Heart attack, stroke or CV death: 6.5%	8.0%

Figures are average changes in body weight from the start of each trial (BMI change for STEP TEENS), using each paper’s main analysis. Different trials enrolled different people, so do not compare rows directly.

STEP 1: the headline trial

STEP 1, published in the New England Journal of Medicine in 2021, enrolled 1,961 adults without diabetes and randomly assigned them, two to one, to weekly semaglutide 2.4 mg or placebo for 68 weeks, both with lifestyle counseling.

• Average weight change: −14.9% with semaglutide versus −2.4% with placebo. In absolute terms that was −15.3 kg (about 34 pounds) versus −2.6 kg.
• Lost at least 5%: 86.4% versus 31.5%.
• Lost at least 10%: 69.1% versus 12.0%.
• Lost at least 15%: 50.5% versus 4.9%.

People on semaglutide also had bigger improvements in heart and metabolic risk factors and reported better physical functioning. Nausea and diarrhea were the most common side effects; they were usually mild to moderate and faded over time. 4.5% of people on semaglutide stopped treatment because of digestive side effects, compared with 0.8% on placebo.

The averages hide a wide range. At a 2021 American Diabetes Association symposium on the STEP program, Dr. Lee Kaplan of Massachusetts General Hospital noted that in STEP 1, about 35% lost more than 20% of their body weight and 11% lost more than 30%, “but some patients fail to respond as well.” Across the program, roughly 7% to 13% of patients overall, and 31% of those with type 2 diabetes, lost less than 5%.

STEP 2: people with type 2 diabetes

STEP 2 enrolled 1,210 adults with overweight or obesity and type 2 diabetes and compared semaglutide 2.4 mg, semaglutide 1.0 mg (the dose then approved for treating diabetes) and placebo for 68 weeks.

• Average weight change: −9.6% with 2.4 mg, −7.0% with 1.0 mg and −3.4% with placebo.
• Lost at least 5%: 68.8% versus 28.5% on placebo.
• HbA1c (a measure of average blood sugar) fell by 1.6 points with 2.4 mg versus 0.4 with placebo.
• Digestive side effects: 63.5% (2.4 mg), 57.5% (1.0 mg) and 34.3% (placebo).

The lesson is simple: people with type 2 diabetes tend to lose less weight on semaglutide than people without it, a pattern also seen with other GLP-1 medicines. A smaller number on the scale can still come with real benefits for blood sugar. For a plain explanation of the two brands, see Wegovy vs Ozempic.

STEP 3: semaglutide plus intensive behavioral therapy

STEP 3 asked whether adding a very structured lifestyle program changes the picture. Its 611 US adults without diabetes had a low-calorie meal-replacement diet for the first 8 weeks and 30 counseling visits over 68 weeks, on top of semaglutide or placebo.

• Average weight change: −16.0% versus −5.7%.
• Lost at least 5%: 86.6% versus 47.6%. At least 10%: 75.3% versus 27.0%. At least 15%: 55.8% versus 13.2%.
• Digestive side effects: 82.8% versus 63.2%, and 3.4% of people on semaglutide stopped because of them (none on placebo).

Intensive counseling more than doubled the placebo group’s result compared with STEP 1, but it added only a little to the semaglutide group’s average. Speakers at the ADA symposium summarized it this way: the lifestyle program sped up early weight loss but did not add much by week 68. That does not mean lifestyle habits are pointless on a GLP-1. They matter for muscle, nutrition and keeping weight off, as discussed in strength training on GLP-1s and what to eat on a GLP-1.

STEP 4 and the STEP 1 extension: what happened after stopping

These two studies are the most important ones for anyone thinking about the long term.

STEP 4 started 902 adults on semaglutide for 20 weeks, during which they lost an average of 10.6%. The 803 who reached the full dose were then randomly assigned either to keep taking semaglutide or to switch, without knowing it, to placebo for another 48 weeks.

• Kept taking semaglutide: lost another 7.9%.
• Switched to placebo: regained 6.9%.
• Waist size, blood pressure and physical functioning were also better in the group that continued.

The STEP 1 extension followed 327 STEP 1 participants for a year after both the medicine and the lifestyle program ended. People on semaglutide had lost 17.3% by week 68. One year after stopping, they had regained 11.6 percentage points, leaving a net loss of 5.6% from where they started. The authors describe this as regaining about two-thirds of the weight lost, and most improvements in blood pressure, cholesterol and blood sugar moved back toward their starting levels. On the positive side, 48.2% still weighed at least 5% less than at the start.

The researchers concluded that the findings “confirm the chronicity of obesity” and that ongoing treatment seems to be needed to maintain the benefits. That is a population average, not a rule for any individual, and it is one reason why stopping or tapering is a conversation to have with your prescriber. Our guide on how to maintain weight loss covers what research shows about keeping weight off, with or without medicine.

STEP 5: two years on treatment

STEP 5 tested whether results last. 304 adults without diabetes took semaglutide 2.4 mg or placebo for 104 weeks, both with behavioral support.

• Average weight change at two years: −15.2% versus −2.6%.
• Lost at least 5%: 77.1% versus 34.4%.
• Digestive side effects: 82.2% versus 53.9%.

The authors describe the loss as substantial and sustained over the full two years, as long as people stayed on treatment. A leveling-off after the first year or so is a common pattern with weight-loss treatments; our GLP-1 weight-loss timeline explains what the trials show month by month, and why weight-loss plateaus happen explains the biology.

STEP 8: semaglutide versus liraglutide

STEP 8 was the first trial to compare semaglutide directly with liraglutide 3.0 mg (sold as Saxenda), an older daily GLP-1 injection. Its 338 US adults without diabetes were followed for 68 weeks. The comparison between the two active drugs was open-label, meaning participants knew which one they were taking.

• Average weight change: −15.8% with semaglutide, −6.4% with liraglutide and −1.9% with placebo.
• Lost at least 15%: 55.6% versus 12.0%.
• Stopped treatment for any reason: 13.5% versus 27.6%.
• Digestive side effects were similar: 84.1% versus 82.7%.

STEP TEENS: adolescents

STEP TEENS enrolled 201 adolescents aged 12 to 17 with obesity (all but one), who took semaglutide 2.4 mg or placebo for 68 weeks with lifestyle support. In teens, results are reported as a change in BMI because they are still growing.

• Average BMI change: −16.1% versus +0.6%.
• Lost at least 5% of body weight: 73% versus 18%.
• Digestive side effects: 62% versus 42%. Five teens (4%) on semaglutide and none on placebo developed gallstones.

Wegovy’s label now includes people aged 12 and older with obesity. Treatment decisions for teenagers are especially individual and involve pediatric specialists.

SELECT: the heart trial

SELECT was designed to answer a different question: does semaglutide protect the heart? It enrolled 17,604 adults aged 45 or older with established cardiovascular disease (a previous heart attack, stroke or peripheral artery disease), a BMI of 27 or more and no diabetes. About 72% were men, unlike most STEP trials.

According to the Wegovy prescribing information, over a median follow-up of about 3.5 years:

• A heart attack, stroke or cardiovascular death occurred in 6.5% on semaglutide versus 8.0% on placebo, a 20% lower relative risk (hazard ratio 0.80).
• Heart attacks (fatal or not): 2.8% versus 3.8%.
• Cardiovascular death on its own: 2.5% versus 3.0%, a difference that did not reach the trial’s bar for a confirmed result.
• 31% of people on semaglutide and 27% on placebo permanently stopped the study drug at some point.

A separate analysis of SELECT found that weight loss continued for about 65 weeks and was sustained for up to four years, with average weight change of −10.2% versus −1.5% at week 208. That is smaller than in STEP 1, which is not surprising in an older group, mostly men, many with other conditions and without an intensive weight-loss program. SELECT’s results are the basis for Wegovy’s approval to reduce the risk of major cardiovascular events in adults with established heart disease and obesity or overweight. They do not tell us whether semaglutide prevents a first heart attack in people without existing cardiovascular disease.

Trials of other health conditions

Several trials have tested semaglutide 2.4 mg in people with specific obesity-related conditions. Each enrolled a particular group, so the results apply mainly to people like those studied.

• Heart failure (STEP-HFpEF): 529 adults with heart failure with preserved ejection fraction and a BMI of 30 or more. Over 52 weeks, symptoms and physical limitations improved more on semaglutide (a 16.6-point increase on a 100-point questionnaire versus 8.7), weight fell 13.3% versus 2.6%, and the 6-minute walk distance improved by 21.5 meters versus 1.2.
• Knee osteoarthritis (STEP 9): 407 adults with obesity and painful knee osteoarthritis. Over 68 weeks, weight fell 13.7% versus 3.2%, and knee pain scores improved more (−41.7 versus −27.5 points on a 100-point scale).
• Fatty liver disease with inflammation (MASH, ESSENCE trial): in the first 800 people with moderate to advanced liver scarring, liver inflammation resolved without worsening scarring in 62.9% versus 34.3% at 72 weeks, and scarring improved in 36.8% versus 22.4%. Weight fell 10.5% versus 2.0%.
• Kidney disease in type 2 diabetes (FLOW): this trial used the 1.0 mg diabetes dose, not the weight-loss dose. In 3,533 people with type 2 diabetes and chronic kidney disease, major kidney events or kidney-related or cardiovascular death were 24% less likely over a median of 3.4 years.

Our What Is Semaglutide? guide lists which of these uses are currently on the US labels.

Higher dose: STEP UP (7.2 mg)

STEP UP tested whether tripling the weekly dose adds more weight loss. It enrolled 1,407 adults with a BMI of 30 or more and no diabetes, assigned five to one to one to 7.2 mg, 2.4 mg or placebo for 72 weeks.

• Average weight change: −18.7% (7.2 mg), −15.6% (2.4 mg) and −3.9% (placebo). The extra benefit of the higher dose was about 3 percentage points.
• People on 7.2 mg were more likely than those on 2.4 mg to lose at least 20% or 25% of their weight.
• Digestive side effects: 70.8%, 61.2% and 42.8%.
• Dysesthesia, an unusual skin sensation such as tingling, sensitivity or burning: 22.9%, 6.0% and 0.5%.

A companion trial, STEP UP T2D, enrolled 512 adults with obesity and type 2 diabetes. Average weight change was −13.2% with 7.2 mg versus −3.9% with placebo, and digestive side effects were reported by 53.1% on 7.2 mg, 51.5% on 2.4 mg and 25.5% on placebo.

The FDA approved the 7.2 mg dose as Wegovy HD on March 19, 2026. The agency’s announcement notes that altered skin sensation was common, happened more often at the higher dose and generally went away on its own or with a dose reduction, and that the FDA is investigating the reaction further. Whether a higher dose makes sense for anyone is a question for their prescriber, weighing the modest extra weight loss against more side effects.

Pills: OASIS 1 and OASIS 4

Semaglutide also comes as a daily tablet. Oral doses are much higher than injected ones, and the pill comes with strict rules about taking it on an empty stomach.

• OASIS 1 tested a 50 mg daily pill in 667 adults without diabetes for 68 weeks: −15.1% versus −2.4%, with digestive side effects in 80% versus 46%. The pill later approved for weight loss uses a lower 25 mg dose.
• OASIS 4 tested a 25 mg daily pill in 307 adults without diabetes for 64 weeks: −13.6% versus −2.2%, with digestive side effects in 74.0% versus 42.2%.

According to a 2026 analysis prepared for regulators, the 25 mg pill was approved for obesity treatment based on earlier semaglutide data and the OASIS program, and most people on it in OASIS 4 reached blood levels similar to those seen with the 2.4 mg weekly injection in STEP 1. For the practical differences, see GLP-1 pills vs injections and oral semaglutide explained.

How semaglutide compares with tirzepatide

Most semaglutide trials compared it with placebo, not with other drugs. The one large head-to-head trial is SURMOUNT-5, funded by Eli Lilly, which makes tirzepatide. In 751 adults with obesity and no diabetes, people took the highest dose they could tolerate of either drug for 72 weeks. Average weight change was −20.2% with tirzepatide versus −13.7% with semaglutide, and waist size fell 18.4 cm versus 13.0 cm. Digestive side effects were the most common problem with both, mostly during dose increases.

Note that the semaglutide result in SURMOUNT-5 was lower than in STEP 1. Different trials, populations and designs give different numbers, which is exactly why comparing results from separate trials is risky. Our Semaglutide vs Tirzepatide guide and What Is Tirzepatide? go into more detail.

Side effects across the trials

The pattern was strikingly consistent: digestive side effects were common, usually mild to moderate, and mostly happened while the dose was being raised.

Trial	Digestive side effects on semaglutide	On placebo
STEP 2 (2.4 mg, diabetes)	63.5%	34.3%
STEP 3	82.8%	63.2%
STEP 4 (after run-in)	49.1%	26.1%
STEP 5	82.2%	53.9%
STEP 8	84.1%	(liraglutide 82.7%)
STEP UP (7.2 mg)	70.8%	42.8%
OASIS 4 (25 mg pill)	74.0%	42.2%

Most people who had these side effects kept taking the medicine; across the trials, only a few percent stopped because of them. Less common but more serious risks, such as gallbladder problems and pancreatitis, are covered in our guides to GLP-1s and gallbladder problems, GLP-1 nausea and constipation and diarrhea, and in the Side Effects hub.

What the trials do not tell you

• Your personal result. Trial averages include people who lost 30% and people who lost almost nothing. Diabetes, sex, how consistently the medicine is taken and many other factors play a part.
• Very long-term effects. The longest weight-loss data come from SELECT (about four years). Effects over decades are still being studied.
• How muscle and fat change for each person. Body composition was measured only in small substudies, and people lose some lean mass along with fat. Protein and resistance exercise are commonly recommended; see how much protein you need on a GLP-1.
• Results with compounded or unapproved products. The trials used the manufacturer’s medicine. They say nothing about the quality of products from other sources.
• What happens in everyday care. Real-world patients are more varied, may get less support, and often face cost and insurance barriers that cause them to stop early. Our GLP-1 costs hub covers that side.

What people are saying online

On X, the semaglutide conversation in recent weeks has focused on new analyses presented at a European diabetes meeting. Several posts described a company-presented, post hoc analysis of about 55 STEP UP participants in which liver fat fell substantially; commentators noted that it was small and exploratory. Other posts debated an indirect comparison by Eli Lilly that combined results from separate tirzepatide and semaglutide trials; more careful accounts pointed out that it was not a head-to-head trial and that the size of the gap depends on which estimand is used. A doctor posting about GLP-1 basics urged people to protect muscle with protein and strength training and to expect nausea to be worst after dose increases.

On YouTube, obesity specialists such as Dr. Robert Kushner of Northwestern University explain that GLP-1 is a natural gut hormone released when you eat that signals fullness to the brain, and that the medicines amplify that signal. That fits the trials: one STEP analysis presented at the ADA symposium reported that energy intake was about 35% lower on semaglutide than on placebo. Online stories are useful for understanding experiences, but for how well the medicine works on average, the trial numbers above are more reliable.

Questions to ask your prescriber

1. Which trial results are most relevant to someone like me (with or without diabetes, heart disease or another condition)?
2. What would count as a good response for me, and when would we judge it?
3. How should I expect side effects to change as the dose goes up?
4. If I need to stop, what does the evidence suggest about weight regain, and how would we plan for it?
5. Are the pill, the standard injection or a higher dose options for me, and what are the trade-offs?
6. What should I do about protein, exercise and muscle while I am losing weight?

The bottom line

Semaglutide’s trial record is unusually large and consistent. In adults without diabetes, the weekly 2.4 mg injection with lifestyle counseling led to average weight loss of about 15% to 16% over 68 weeks versus a few percent on placebo, with smaller results in people with type 2 diabetes. Results held for at least two years while people stayed on it, but most of the weight returned within a year of stopping. In people with established heart disease, SELECT showed a 20% lower risk of major cardiovascular events. A higher 7.2 mg dose added about 3 percentage points of weight loss with more side effects, and a daily 25 mg pill produced results in a similar range to the injection. Digestive side effects were common throughout. The averages are a useful guide, but your own result, and the right choice for you, depend on your health and your prescriber’s advice.

Explore more in the Semaglutide hub, compare options in the GLP-1 Guide hub, or see Tirzepatide Clinical Trial Results, Summarized for the other side. You can also check where you stand with the BMI calculator.