If you’re thinking about a GLP-1 medicine, you probably want to know how much weight people really lose. The most reliable answers come from large randomized trials. In these studies, people were assigned by chance to take the medicine or a placebo (a look-alike shot or pill with no medicine in it), and their weight was tracked for more than a year [1, 2].
Below is what the main trials of semaglutide (Wegovy), tirzepatide (Zepbound) and orforglipron (Foundayo) found. Tirzepatide acts on the targets of two natural hormones, GLP-1 and GIP [3]. The numbers describe groups of people in research studies. They aren’t a promise of what will happen to you.
How to read trial results
Trials report weight change as a percentage of starting weight. For someone who weighs 200 pounds, a 15% loss would be 30 pounds. Losing 5% to 10% of your starting weight may help lower blood sugar, blood pressure and some blood fats [4].
Always compare the medicine group with the placebo group. In STEP 1 and SURMOUNT-1, both groups got the same advice on eating and activity, so the gap between them shows what the medicine added [3, 5].
The main trials at a glance
These five trials lasted 64 to 72 weeks (about 15 to 17 months), and none included people with type 2 diabetes. Obesity means a BMI (body mass index, a measure of weight relative to height) of 30 or more [4]. Most of the trials also enrolled people with a BMI of 27 to 29.9 who had a weight-related condition, such as high blood pressure [3, 5, 6]. In the table, “vs.” compares the medicine with placebo unless noted.
| Trial | Medicine and dose | Who took part | Length | Average weight change | Share who lost at least 5% / 10% / 15% |
|---|---|---|---|---|---|
| STEP 1 [1] | Semaglutide (Wegovy) 2.4 mg shot, once a week | 1,961 adults | 68 weeks | −14.9% vs. −2.4% | 86.4% / 69.1% / 50.5% vs. 31.5% / 12.0% / 4.9% |
| SURMOUNT-1 [2, 3] | Tirzepatide (Zepbound) 5, 10 or 15 mg shot, once a week | 2,539 adults | 72 weeks | −15.0% (5 mg), −19.5% (10 mg) and −20.9% (15 mg) vs. −3.1% | At 15 mg: 90.9% / 83.5% / 70.6% vs. 34.5% / 18.8% / 8.8% |
| SURMOUNT-5 [7] | Tirzepatide 10 or 15 mg vs. semaglutide 1.7 or 2.4 mg, shots once a week | 751 adults with obesity | 72 weeks | −20.2% with tirzepatide vs. −13.7% with semaglutide (no placebo group) | More people on tirzepatide lost at least 10%, 15%, 20% and 25% |
| OASIS 4 [5] | Semaglutide (Wegovy) 25 mg tablet, once a day | 307 adults | 64 weeks | −13.6% vs. −2.4% | 76.3% / 59.8% / 47% vs. 31.3% / 14.4% / 5.5% |
| ATTAIN-1 [6] | Orforglipron (Foundayo) 5.5, 9 or 17.2 mg tablet, once a day | 3,127 adults | 72 weeks | −7.4% (5.5 mg), −8.3% (9 mg) and −11.1% (17.2 mg) vs. −2.1% | At 17.2 mg: 71.5% / 54.5% / 35.9% vs. 26.8% / 13% / 6% |
A few notes on the table:
- SURMOUNT-5 compared the two medicines head to head, at the highest dose each person could tolerate. Participants knew which medicine they were taking (an “open-label” trial) [7].
- The published ATTAIN-1 report lists doses of 6, 12 and 36 mg of an earlier, experimental version of the pill; the FDA label shows the equivalent doses of the approved tablet [6, 8].
- The current Wegovy label also allows a higher 7.2 mg weekly dose for adults who have tolerated 2.4 mg for at least 4 weeks, if their clinician decides more weight loss is needed. In a 72-week trial of 1,407 adults with obesity, average weight change was −18.8% with 7.2 mg, −15.5% with 2.4 mg and −3.9% with placebo [5].
- Journal articles and FDA labels sometimes analyze the same trial differently, so numbers can differ slightly. For example, the OASIS 4 paper reports a 2.2% average loss with placebo; the label reports 2.4% [5, 9]. Shares for SURMOUNT-1, OASIS 4 and ATTAIN-1 come from the labels [3, 5, 6].
Averages hide a wide range
An average sits in the middle of a wide spread, and results vary from person to person [4]. For example:
- In STEP 1, half the people on semaglutide (50.5%) lost at least 15% of their weight, but about 1 in 7 lost less than 5% [1].
- With tirzepatide 15 mg in SURMOUNT-1, 56.7% lost 20% or more, while about 9 in 100 lost less than 5% [3].
- With orforglipron 17.2 mg, 18.4% lost 20% or more, while about 3 in 10 lost less than 5% [6].
No one can predict exactly where you’ll land.
The results came with a lifestyle program
In the placebo-controlled trials above, everyone got advice on eating and activity [3, 5, 6]. In STEP 1 and SURMOUNT-1, that meant counseling on a diet with about 500 fewer calories a day and at least 150 minutes of physical activity a week [3, 5]. The placebo groups lost some weight, too: about 1 in 3 people on placebo lost at least 5% (31.5% in STEP 1 and 35% in SURMOUNT-1) [1, 2].
Trial counseling was also more frequent and structured than usual care. A 2025 joint advisory from four professional societies says this may help explain why real-world weight loss is modestly lower than in trials [10]. Medicines don’t replace healthy eating and activity; they work best with a lifestyle program [4].
People with type 2 diabetes tend to lose less
Separate trials tested these medicines in adults with type 2 diabetes and a BMI of 27 or more [6, 11, 12]. Average weight loss was smaller:
- STEP 2: semaglutide 2.4 mg once a week for 68 weeks led to −9.6% vs. −3.4% with placebo [11], compared with −14.9% in STEP 1 [1].
- SURMOUNT-2: tirzepatide 10 or 15 mg once a week for 72 weeks led to −12.8% and −14.7% vs. −3.2% with placebo [12], compared with −19.5% and −20.9% at the same doses in SURMOUNT-1 [2].
- A 72-week orforglipron trial: −9.6% with 17.2 mg vs. −2.5% with placebo, compared with −11.1% in ATTAIN-1 [6].
These comparisons span different trials, so they’re rough. People with diabetes did see bigger drops in A1c, a blood sugar measure (see below) [3, 5].
Weight loss slows, then levels off
Weight loss is fastest in the first months and then slows [4, 10]. In semaglutide trials, average weight leveled off at around week 60 and was then maintained; in the 2-year STEP 5 trial, average loss at the end was 15.2% vs. 2.6% with placebo [13]. In SELECT, a large heart trial in people who hadn’t enrolled to lose weight, weight loss continued to week 65, then held steady for up to 4 years [14].
For tirzepatide, a later analysis of SURMOUNT-1 looked at people who kept taking it and lost at least 5%. It defined a plateau as losing less than 5% more over 12 weeks. By week 72, 87.6% to 90.2% had reached a plateau, depending on their starting BMI [15]. Among SURMOUNT-1 participants with prediabetes, whose treatment continued for 176 weeks (about 3.4 years), average weight loss at that point was 12.3% to 19.7%, depending on the dose, vs. 1.3% with placebo [16].
A plateau happens with every weight-loss treatment [14].
Some of the weight lost is lean mass
Losing weight, especially quickly, often means losing some lean mass (muscle and other non-fat tissue) along with fat [10]. Body scans show how much:
- In a body-scan study of 160 SURMOUNT-1 participants, those on tirzepatide lost 33.9% of their fat mass and 10.9% of their lean mass over 72 weeks. About 75% of the weight lost was fat and 25% was lean mass, and the split was about the same in the placebo group [17].
- The joint advisory reports STEP 1 body-scan results: of an average 13.6 kg (about 30 pounds) lost, 62% was fat and 38% was lean mass [10].
The advisory notes that these losses are similar to those seen with other treatments that cause large weight loss, such as bariatric surgery and very low-calorie diets. Strength training, along with enough protein, can help preserve muscle [10]. Learn more in eating well on a GLP-1.
Health changes seen in the trials
The trials also tracked waist size, systolic blood pressure (the top number, the pressure when your heart beats) [18] and A1c, a blood test of your average blood sugar over the past 3 months [19]. The table shows average changes at the end of each trial (medicine vs. placebo).
| Trial and dose | Waist size | Systolic blood pressure | A1c (percentage points) |
|---|---|---|---|
| STEP 1: semaglutide 2.4 mg [5] | −13.5 cm vs. −4.1 cm | −6.2 vs. −1.1 mm Hg | −0.4 vs. −0.2 |
| SURMOUNT-1: tirzepatide 15 mg [3] | −18.5 cm vs. −4.0 cm | −7.4 vs. −1.0 mm Hg | −0.4 vs. −0.1 |
| OASIS 4: semaglutide tablet 25 mg [5] | −12.2 cm vs. −2.8 cm | −7 vs. −5.4 mm Hg | −0.3 vs. −0.1 |
| ATTAIN-1: orforglipron 17.2 mg [6] | −10 cm vs. −3.1 cm | −6.4 vs. −1.4 mm Hg | −0.3 vs. −0.1 |
| STEP 2 (type 2 diabetes): semaglutide 2.4 mg [5] | −9.4 cm vs. −4.5 cm | −3.9 vs. −0.5 mm Hg | −1.6 vs. −0.4 |
| SURMOUNT-2 (type 2 diabetes): tirzepatide 15 mg [3] | −13.1 cm vs. −3.3 cm | −7.1 vs. −1.2 mm Hg | −2.1 vs. −0.5 |
One inch is 2.54 cm. People without diabetes started with an average A1c of 5.5% to 5.7%, and people with diabetes at 8.0% to 8.1% [3, 5, 6]. In SURMOUNT-5, waist size shrank by 18.4 cm on average with tirzepatide vs. 13.0 cm with semaglutide [7].
Side effects, and what happens if you stop
The most common side effects were digestive, such as nausea and diarrhea. Most were mild to moderate; in STEP 1 they usually eased with time, and in SURMOUNT-1 they happened mostly while the dose was being raised [1, 2]. In STEP 1, 4.5% of people on semaglutide stopped because of digestive side effects, vs. 0.8% on placebo. In SURMOUNT-1, 4.3% to 7.1% on tirzepatide stopped because of any side effect, vs. 2.6% on placebo [1, 2]. Resting heart rate also rose slightly, by 3.5 beats per minute on average with semaglutide in STEP 1, vs. a 0.7 drop with placebo [5]. Read more about GLP-1 side effects.
Weight tends to come back after stopping. In one trial, people lost an average of 20.9% of their weight on tirzepatide over 36 weeks. Those then switched to placebo saw their weight rise by 14.0% over the next 52 weeks, while those who stayed on tirzepatide lost another 5.5% [3]. A similar semaglutide trial found a 6.9% rise over 48 weeks on placebo, vs. a further 7.9% loss on semaglutide [5]. See stopping a GLP-1 for more.
The bottom line
In large trials of people without diabetes, average weight loss ranged from about 7% to 21% over 64 to 72 weeks, depending on the medicine and dose, vs. about 2% to 4% with placebo [1, 2, 5, 6]. These results came with diet and activity counseling, and people with type 2 diabetes lost less on average [11, 12]. Results varied widely from person to person, weight loss leveled off within about a year and a half, and part of the loss was lean mass [4, 13, 15, 17]. Side effects were common, and weight tended to return after stopping [3, 5].
References
- Wilding JPH, et al. Once-weekly semaglutide in adults with overweight or obesity. New England Journal of Medicine. 2021. https://pubmed.ncbi.nlm.nih.gov/33567185/
- Jastreboff AM, et al. Tirzepatide once weekly for the treatment of obesity. New England Journal of Medicine. 2022. https://pubmed.ncbi.nlm.nih.gov/35658024/
- Eli Lilly and Company. Zepbound (tirzepatide) injection: prescribing information and medication guide. DailyMed, U.S. National Library of Medicine. Label revised August 2026 (effective August 28, 2026). https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=487cd7e7-434c-4925-99fa-aa80b1cc776b
- National Institute of Diabetes and Digestive and Kidney Diseases. Prescription medications to treat overweight & obesity. National Institutes of Health. 2024. https://www.niddk.nih.gov/health-information/weight-management/prescription-medications-treat-overweight-obesity
- Novo Nordisk. Wegovy (semaglutide) injection and tablets: prescribing information and medication guide. DailyMed, U.S. National Library of Medicine. Label revised June 2026 (effective June 18, 2026). https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ee06186f-2aa3-4990-a760-757579d8f77b
- Eli Lilly and Company. Foundayo (orforglipron) tablets: prescribing information and medication guide. DailyMed, U.S. National Library of Medicine. Label revised July 2026 (effective July 29, 2026). https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8ac446c5-feba-474f-a103-23facb9b5c62
- Aronne LJ, et al. Tirzepatide as compared with semaglutide for the treatment of obesity. New England Journal of Medicine. 2025. https://pubmed.ncbi.nlm.nih.gov/40353578/
- Wharton S, et al. Orforglipron, an oral small-molecule GLP-1 receptor agonist for obesity treatment. New England Journal of Medicine. 2025. https://pubmed.ncbi.nlm.nih.gov/40960239/
- Wharton S, et al. Oral semaglutide at a dose of 25 mg in adults with overweight or obesity. New England Journal of Medicine. 2025. https://pubmed.ncbi.nlm.nih.gov/40934115/
- Mozaffarian D, et al. Nutritional priorities to support GLP-1 therapy for obesity: a joint advisory from the American College of Lifestyle Medicine, the American Society for Nutrition, the Obesity Medicine Association, and The Obesity Society. Obesity. 2025. https://pubmed.ncbi.nlm.nih.gov/40445127/
- Davies M, et al. Semaglutide 2·4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2): a randomised, double-blind, double-dummy, placebo-controlled, phase 3 trial. Lancet. 2021. https://pubmed.ncbi.nlm.nih.gov/33667417/
- Garvey WT, et al. Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. 2023. https://pubmed.ncbi.nlm.nih.gov/37385275/
- Garvey WT, et al. Two-year effects of semaglutide in adults with overweight or obesity: the STEP 5 trial. Nature Medicine. 2022. https://pubmed.ncbi.nlm.nih.gov/36216945/
- Ryan DH, et al. Long-term weight loss effects of semaglutide in obesity without diabetes in the SELECT trial. Nature Medicine. 2024. https://pubmed.ncbi.nlm.nih.gov/38740993/
- Horn DB, et al. Time to weight plateau with tirzepatide treatment in the SURMOUNT-1 and SURMOUNT-4 clinical trials. Clinical Obesity. 2025. https://pubmed.ncbi.nlm.nih.gov/39800653/
- Jastreboff AM, et al. Tirzepatide for obesity treatment and diabetes prevention. New England Journal of Medicine. 2025. https://pubmed.ncbi.nlm.nih.gov/39536238/
- Look M, et al. Body composition changes during weight reduction with tirzepatide in the SURMOUNT-1 study of adults with obesity or overweight. Diabetes, Obesity and Metabolism. 2025. https://pubmed.ncbi.nlm.nih.gov/39996356/
- MedlinePlus. High blood pressure. U.S. National Library of Medicine. 2026. https://medlineplus.gov/highbloodpressure.html
- National Institute of Diabetes and Digestive and Kidney Diseases. The A1C test & diabetes. National Institutes of Health. 2018. https://www.niddk.nih.gov/health-information/diagnostic-tests/a1c-test
This article is for education only and isn’t a substitute for advice from your own clinician.