Semaglutide Results: What Clinical Trials Actually Show

You searched for semaglutide before and after. You want to know what people actually experience.

The most honest answer comes from the clinical trials, not from social media posts or testimonials. The STEP 1 trial (semaglutide, 1,961 adults) and SURMOUNT-1 trial (tirzepatide, 2,539 adults) were both published in the New England Journal of Medicine^[1][2]. The SELECT trial added cardiovascular outcome data for semaglutide in people without diabetes^[4].

This page covers what those trials actually showed, what the week-by-week experience typically looks like, and why individual results vary so significantly.

One important framing note before we start: all clinical trial data on this page reflects results from FDA-approved brand-name medications. Compounded formulations of semaglutide and tirzepatide are not FDA-approved and have not been evaluated by the FDA for safety, effectiveness, or quality. Clinical trial results for brand-name products cannot be assumed to apply to compounded versions.

For a side-by-side look at the medications, visit Compare GLP-1 Medications.

The STEP 1 trial: semaglutide outcomes

The STEP 1 trial was published in the New England Journal of Medicine in 2021. It was a randomized, double-blind, placebo-controlled trial conducted across multiple countries and funded by Novo Nordisk, which makes Wegovy^[1].

Who was in the trial

STEP 1 enrolled 1,961 adults with either obesity (BMI 30 or above) or overweight (BMI 27 or above) with at least one weight-related condition. Participants did not have diabetes^[1]. This is an important detail because semaglutide’s weight loss evidence in people without diabetes is what is most relevant to most people considering a GLP-1 medication for weight management.

All participants received a lifestyle intervention (counseling on diet and physical activity) alongside either the medication or placebo. This is also important: the trial was not studying medication alone, but medication as part of a supported program.

What the trial found

Over 68 weeks, participants taking semaglutide 2.4mg weekly had^[1]:

• Average body weight change: -14.9% (about -15.3 kg, or roughly 33.7 lbs, from baseline)
• 86.4% of participants lost 5% or more of body weight (vs 31.5% on placebo)
• 69.1% lost 10% or more (vs 12.0% on placebo)
• 50.5% lost 15% or more (vs 4.9% on placebo)
• Greater improvements in cardiometabolic risk factors than placebo

The placebo group, also receiving lifestyle counseling, had an average change of -2.4% over the same period. The difference between the two groups reflects the medication’s effect above and beyond lifestyle support alone.

What the trial does not tell you

The 14.9% figure is a group average. Individual responses in the trial ranged widely. Some participants lost substantially more; some lost substantially less. The figure describes the group, not a prediction for any individual.

The trial also ended at 68 weeks. A STEP 1 extension tracked a subset of participants after they stopped and found substantial weight regain, which is discussed in more detail below^[3].

The SURMOUNT-1 trial: tirzepatide outcomes

The SURMOUNT-1 trial was published in the New England Journal of Medicine in 2022. It was a randomized, double-blind, placebo-controlled trial funded by Eli Lilly, which makes Zepbound^[2].

Who was in the trial

SURMOUNT-1 enrolled 2,539 adults with obesity or overweight with at least one weight-related complication, without diabetes. Participants were randomized to three dose levels of tirzepatide (5mg, 10mg, or 15mg weekly) or placebo for 72 weeks, including a 20-week dose-escalation period^[2]. All participants received lifestyle counseling.

What the trial found

Over 72 weeks, outcomes at the highest studied dose (15mg weekly) were^[2]:

• Average body weight change: -20.9%
• 91% of participants lost at least 5%
• 57% lost at least 20%

The lower dose groups had lower averages: -15.0% at 5mg and -19.5% at 10mg. This matters because the Zepbound label lists 5mg, 10mg, and 15mg as maintenance doses, and a prescriber chooses among them based on response and tolerability^[9].

The placebo group had an average change of -3.1% over the same period.

The comparison to STEP 1

STEP 1 and SURMOUNT-1 were separate trials with different participants and lengths (68 vs 72 weeks), so their results cannot be compared directly.

The one trial that compared the two medications head to head is SURMOUNT-5, published in the New England Journal of Medicine in 2025. In it, 751 adults with obesity but without type 2 diabetes took the highest dose they tolerated of tirzepatide (10mg or 15mg) or semaglutide (1.7mg or 2.4mg) once a week for 72 weeks. Average weight change was -20.2% with tirzepatide and -13.7% with semaglutide. The trial was open-label (participants knew which medication they took) and was funded by Eli Lilly^[5].

These are averages. Some people do better on semaglutide than some people on tirzepatide. Which medication may be appropriate for your situation is a question for a licensed provider.

The SELECT trial: cardiovascular outcomes

The SELECT trial (Semaglutide Effects on Heart Disease and Stroke in Patients with Overweight or Obesity) looked at heart outcomes rather than weight loss as its main goal.

Who was in the trial

SELECT enrolled 17,604 adults aged 45 or older with preexisting cardiovascular disease and a BMI of 27 or higher, without diabetes^[4]. It was an event-driven, double-blind, placebo-controlled trial designed to assess cardiovascular outcomes, funded by Novo Nordisk.

What the trial found

Over a mean follow-up of 39.8 months, participants taking brand-name semaglutide 2.4mg weekly had^[4]:

• Fewer major adverse cardiovascular events (MACE): 6.5% of the semaglutide group vs 8.0% of the placebo group had one. MACE was defined as cardiovascular death, nonfatal heart attack, or nonfatal stroke.
• A hazard ratio of 0.80 (95% confidence interval 0.72 to 0.90), meaning about 20% lower risk over the trial period.
• More people stopping treatment because of side effects: 16.6% on semaglutide vs 8.2% on placebo.

The results were published in the New England Journal of Medicine in 2023. The Wegovy label now includes reducing the risk of major cardiovascular events in adults with established cardiovascular disease and either obesity or overweight^[8].

What SELECT means for providers

For people with a history of cardiovascular disease and obesity or overweight, the SELECT data adds a layer to the clinical conversation beyond weight loss alone. A licensed provider weighs this evidence alongside your health history when deciding whether a GLP-1 medication may be appropriate.

These results are for the brand-name medication studied in the trial. They cannot be assumed to apply to compounded formulations.

Week-by-week realistic expectations

The headline trial outcomes were measured at 68-72 weeks. Understanding what the early weeks look like sets realistic expectations.

Weeks 1-4: dose adjustment

The labels start both medications at a low dose. Wegovy injection starts at 0.25mg weekly for 4 weeks; Zepbound starts at 2.5mg weekly for 4 weeks^[8][9]. These starting doses are well below the doses that produced the trial outcomes.

How much appetite change people notice at the starting dose varies. Some people notice mild nausea, reduced appetite, or other stomach symptoms as their body adjusts. The first month is not representative of what the medication may feel like at maintenance doses.

Expecting significant weight loss in weeks 1-4 is not consistent with how dose escalation works. What this period is for is establishing tolerability and giving your body time to adjust.

Weeks 4-12: more pronounced effects

As doses increase through the schedule, some people notice more appetite change. Some describe a quieting of the persistent background thoughts about food that is often called “food noise.”

The rate of loss varies by individual. Your starting weight, health history, activity level, and how well you tolerate each dose increase can all play a part during this window.

Months 3-6: continued progress

On the Wegovy label, the maintenance dose starts at week 17. On the Zepbound label, each 2.5mg step comes after at least 4 weeks, so reaching 15mg takes at least 20 weeks^[8][9]. In the STEP 4 trial, people who completed a 20-week semaglutide run-in had lost an average of 10.6% by week 20^[6].

Habits built during this period matter too. The trials that produced the published results included lifestyle counseling for everyone, including the placebo groups, so the results describe medication plus that support.

Months 6 and beyond

In the trials, average weight loss continued after the first months but more slowly. In STEP 4, people who stayed on semaglutide lost a further 7.9% between weeks 20 and 68^[6]. In SURMOUNT-4, people who stayed on tirzepatide after a 36-week lead-in lost a further 5.5% between weeks 36 and 88^[7]. A slowdown while still taking the medication is normal. Weight loss does not continue in a straight line indefinitely.

This is also the phase where conversations with your prescriber about maintenance, dose adjustment, and long-term planning become relevant.

Why individual results vary significantly

Group averages from clinical trials describe the middle of a wide range. Understanding why individual responses vary helps set realistic expectations.

Starting weight

The percentage of body weight lost is a more consistent measure than absolute pounds, but absolute numbers matter for how progress feels. Someone starting at 220 lbs and losing 15% loses 33 lbs. Someone starting at 180 lbs and losing 15% loses 27 lbs. The percentage can be similar while the absolute numbers differ.

Metabolic health history

Past weight cycling, earlier calorie restriction, and other medical history differ from person to person. The trials report averages and were not designed to predict how any one person with a given history will respond.

Dose achieved

In SURMOUNT-1, average weight loss was higher at 10mg and 15mg than at 5mg^[2]. Not everyone reaches or stays on the highest dose. Some people have tolerability issues with higher doses and stay at a moderate level. A prescriber adjusts dosing based on response and side effects rather than aiming for the highest dose at any cost.

Lifestyle factors

Both STEP 1 and SURMOUNT-1 paired the medication with a lifestyle intervention for every participant^[1][2]. GLP-1 medications reduce appetite signals, but they work within a larger context of how you eat and move.

Hormonal status

For perimenopausal and postmenopausal women, hormonal changes can affect where the body stores fat and how weight changes. The trials enrolled women across a range of ages, but the averages above are for the whole trial population, not for any menopausal stage. Hormonal context is part of the clinical picture a licensed provider considers.

Duration of treatment

The 15% and 20% averages from STEP 1 and SURMOUNT-1 were measured after 68-72 weeks^[1][2]. Earlier time points showed less loss (10.6% at week 20 in the STEP 4 run-in^[6]). Stopping the medication is linked to weight regain, as described below.

What happens when you stop

This is the question that deserves a direct answer.

A STEP 1 extension, published in Diabetes, Obesity and Metabolism (2022), followed 327 participants for one year after semaglutide and the lifestyle program ended. They regained about two-thirds of the weight they had lost, and most cardiometabolic improvements (such as blood pressure and blood sugar) moved back toward baseline^[3].

Two withdrawal trials point the same way. In STEP 4, people who switched from semaglutide to placebo at week 20 gained 6.9% over the next 48 weeks, while those who continued lost a further 7.9%^[6]. In SURMOUNT-4, people switched from tirzepatide to placebo at week 36 gained 14.0% over the next 52 weeks, while those who continued lost a further 5.5%^[7].

This is not a failure of the medication. It reflects the underlying biology of weight regulation: the appetite signals that GLP-1 medications act on return when the medication is stopped.

Using the treatment phase to build habits around eating, activity, and sleep is worth doing for its own sake. Whether to continue, adjust the dose, or stop is a decision to make with your prescriber as part of the long-term plan.

Side effects and safety

Benefits only tell half the story. Here is what the current FDA labels say about risk.

Common side effects. The most common side effects of Wegovy include nausea, diarrhea, vomiting, constipation, abdominal pain, abnormal skin sensations (dysesthesia), headache, fatigue, indigestion, dizziness, bloating, burping, low blood sugar in people with type 2 diabetes, gas, stomach flu, reflux, and hair loss^[8]. The most common side effects of Zepbound include nausea, diarrhea, vomiting, constipation, abdominal pain, indigestion, injection site reactions, fatigue, allergic reactions, burping, hair loss, and reflux^[9].

Boxed warning and who should not use them. Both labels carry a boxed warning about thyroid C-cell tumors seen in rodents. It is unknown whether either medication causes these tumors, including medullary thyroid carcinoma, in humans. Neither should be used by people with a personal or family history of medullary thyroid carcinoma or with Multiple Endocrine Neoplasia syndrome type 2, or by people with a known serious allergy to the medication^[8][9].

Other warnings. Both labels also warn about acute pancreatitis, gallbladder disease, low blood sugar when used with insulin or sulfonylureas, kidney injury from dehydration, severe stomach and bowel reactions, serious allergic reactions, diabetic retinopathy complications in people with type 2 diabetes, and the risk of inhaling stomach contents during anesthesia or deep sedation^[8][9]. Read the full labels linked in the citations, and ask a licensed provider how these risks apply to you.

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What’s in this section

This sub-pillar covers specific results topics in more depth:

Tirzepatide Before and After What the SURMOUNT trials of brand-name tirzepatide found at each dose and over time, why social media posts are not typical, and the risks to weigh alongside the results.

How Much Weight Can You Lose on Semaglutide A detailed breakdown of STEP trial outcomes, how results ranged across participants, and how semaglutide compared with tirzepatide in the one head-to-head trial.

Weight Loss Timeline: Week by Week How the FDA labels schedule dose increases, what the STEP and SURMOUNT trials reported at each stage, and why the early weeks often feel slow.

Semaglutide Before and After 1 Month What the first month on semaglutide typically looks like, why early results are limited, and what the first 30 days are actually for.

GLP-1 Clinical Trials: Landmark Study Results A reference guide to STEP 1, STEP 2, STEP 4, SURMOUNT-1, SURMOUNT-4, SURMOUNT-5, SELECT, FLOW, SURMOUNT-OSA, ESSENCE, and SYNERGY-NASH, with populations and key findings.

For a side-by-side comparison of GLP-1 medications, see Compare GLP-1 Medications.

Citations

[1] Wilding JPH, Batterham RL, Calanna S, et al. “Once-Weekly Semaglutide in Adults with Overweight or Obesity.” N Engl J Med. 2021;384(11):989-1002. https://pubmed.ncbi.nlm.nih.gov/33567185/ (STEP 1: 1,961 adults; -14.9% vs -2.4% at 68 weeks; responder rates; funded by Novo Nordisk.)

[2] Jastreboff AM, Aronne LJ, Ahmad NN, et al. “Tirzepatide Once Weekly for the Treatment of Obesity.” N Engl J Med. 2022;387(3):205-216. https://pubmed.ncbi.nlm.nih.gov/35658024/ (SURMOUNT-1: 2,539 adults; -15.0%, -19.5%, -20.9% vs -3.1% at 72 weeks; supported by Eli Lilly.)

[3] Wilding JPH, Batterham RL, Davies M, et al. “Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension.” Diabetes Obes Metab. 2022;24(8):1553-1564. https://pubmed.ncbi.nlm.nih.gov/35441470/ (327 participants; two-thirds of prior weight loss regained one year after stopping.)

[4] Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. “Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes.” N Engl J Med. 2023;389(24):2221-2232. https://pubmed.ncbi.nlm.nih.gov/37952131/ (SELECT: 17,604 adults; 6.5% vs 8.0%, HR 0.80; mean follow-up 39.8 months; discontinuation for adverse events 16.6% vs 8.2%.)

[5] Aronne LJ, Horn DB, le Roux CW, et al. “Tirzepatide as Compared with Semaglutide for the Treatment of Obesity.” N Engl J Med. 2025;393(1):26-36. https://pubmed.ncbi.nlm.nih.gov/40353578/ (SURMOUNT-5: 751 adults, open-label, 72 weeks; -20.2% vs -13.7%; funded by Eli Lilly.)

[6] Rubino D, Abrahamsson N, Davies M, et al. “Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity: The STEP 4 Randomized Clinical Trial.” JAMA. 2021;325(14):1414-1425. https://pubmed.ncbi.nlm.nih.gov/33755728/ (10.6% during the 20-week run-in; -7.9% continued vs +6.9% placebo from week 20 to 68.)

[7] Aronne LJ, Sattar N, Horn DB, et al. “Continued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity: The SURMOUNT-4 Randomized Clinical Trial.” JAMA. 2024;331(1):38-48. https://pubmed.ncbi.nlm.nih.gov/38078870/ (20.9% during the 36-week lead-in; -5.5% continued vs +14.0% placebo from week 36 to 88.)

[8] U.S. Food and Drug Administration. WEGOVY (semaglutide) injection and tablets, prescribing information. Revised 06/2026. https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/215256s025lbl.pdf

[9] U.S. Food and Drug Administration. ZEPBOUND (tirzepatide) injection, prescribing information. Revised 08/2026. https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/217806Orig1s041correctedlbl.pdf