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Comparisons

Best GLP-1 for weight loss: how do the approved options rank in trials?

There is no single best GLP-1 for everyone. There is a clear order in how much weight people lost in the main trials, plus other things that matter as much: pill or shot, heart, kidney, liver or sleep apnea benefits, side effects and coverage. Here is what the evidence shows.

By 8 min read
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The short version
  • For weight loss alone, tirzepatide (Zepbound) has the strongest results: 20.2% average loss vs 13.7% for semaglutide (Wegovy) in SURMOUNT-5, the only head-to-head trial, in adults with obesity and without diabetes.7
  • In the main placebo-controlled trials, average loss ranged from 20.9% (tirzepatide 15 mg) down to about 7% (liraglutide 3.0 mg, Saxenda). Comparing across separate trials is rough.1,13
  • "Best" also depends on proven benefits for other conditions (heart, kidney, sleep apnea, liver), pill or shot, side effects and coverage. That choice belongs with your prescriber.

How do the GLP-1 medicines rank for weight loss?

This table lists the main placebo-controlled trial for each option approved for weight management in the US, in adults with obesity, or overweight plus a weight-related condition, and without diabetes. Everyone, including the placebo groups, also got diet and activity advice.

Medicine (brand)FormTrialLengthAverage weight changePlacebo
Tirzepatide 15 mg (Zepbound)Weekly shotSURMOUNT-1, 2,539 adults72 weeks−20.9%−3.1%
Semaglutide 7.2 mg (Wegovy)Weekly shotSTEP UP, 1,407 adults with BMI 30+72 weeks−18.7%−3.9%
Semaglutide 2.4 mg (Wegovy)Weekly shotSTEP 1, 1,961 adults68 weeks−14.9%−2.4%
Oral semaglutide 25 mg (Wegovy pill)Daily pillOASIS 4, 307 adults64 weeks−13.6%−2.2%
Orforglipron 36 mg (Foundayo 17.2 mg)Daily pillATTAIN-1, 3,127 adults72 weeks−11.2%−2.1%
Liraglutide 3.0 mg (Saxenda)Daily shotSCALE, 3,731 adults56 weeks−7.4%−3.0%
 Sources: Jastreboff 2022, Wharton 2025 (STEP UP), Wilding 2021, Wharton 2025 (OASIS 4), Wharton 2025 (ATTAIN-1), Saxenda prescribing information section 14 (SCALE).1–6,13 Lower tirzepatide doses: −15.0% (5 mg) and −19.5% (10 mg).
Tirzepatide 15 mg−20.9%
Semaglutide 7.2 mg−18.7%
Semaglutide 2.4 mg−14.9%
Wegovy pill 25 mg−13.6%
Orforglipron (top dose)−11.2%
Liraglutide 3.0 mg−7.4%
These are separate trials with different people, lengths and years. Placebo groups lost 2% to 4%, which shows how much the settings differed. Treat the order as a rough guide. The SCALE figure is from the Saxenda label; the published paper reported 8.4 kg vs 2.8 kg lost.6,13
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What did the head-to-head trial show?

SURMOUNT-5 is the only trial that randomly assigned people to two of these medicines. It enrolled 751 adults with obesity and without type 2 diabetes and gave each the highest dose they tolerated: tirzepatide 10 or 15 mg, or semaglutide 1.7 or 2.4 mg, weekly for 72 weeks.7

Tirzepatide−20.2%
Semaglutide−13.7%

Waist size fell by 18.4 cm vs 13.0 cm. Side effects in both groups were mostly stomach-related and mild to moderate. The trial was open-label and funded by Eli Lilly, which makes tirzepatide, and it did not test the newer 7.2 mg semaglutide dose.7 Details: semaglutide vs tirzepatide.

In STEP UP, semaglutide 7.2 mg led to more weight loss than 2.4 mg in the same trial (18.7% vs 15.6%).2 See Wegovy 7.2 mg.

Best GLP-1 depends on more than weight

Some of these medicines have large outcome trials showing benefits beyond the scale. Those benefits are written into the US labels for specific products and specific groups of people.

ConditionTrialWhoResultLabeled for
Heart diseaseSELECT17,604 adults 45+ with heart disease, BMI 27+, no diabetesHeart attack, stroke or CV death: 6.5% on semaglutide 2.4 mg vs 8.0% on placebo (20% lower risk)Wegovy shot and pill
Kidney disease with type 2 diabetesFLOW3,533 adults with type 2 diabetes and chronic kidney disease24% lower risk of major kidney events or kidney or CV death on semaglutide 1.0 mgOzempic
Obstructive sleep apneaSURMOUNT-OSAAdults with obesity and moderate to severe sleep apneaBreathing pauses per hour fell by 25.3 vs 5.3 (no CPAP) and 29.3 vs 5.5 (on CPAP) over 52 weeksZepbound
MASH (fatty liver with inflammation) and fibrosisESSENCE800 adults with biopsy-proven MASH, fibrosis stage 2 or 3Liver inflammation resolved in 62.9% vs 34.3%; fibrosis improved in 36.8% vs 22.4% at 72 weeksWegovy shot (accelerated approval)
 Sources: SELECT, FLOW, SURMOUNT-OSA, ESSENCE and current US labels, section 1.8–11,13 CV = cardiovascular.

Mounjaro, Ozempic and Rybelsus also carry heart-risk indications for adults with type 2 diabetes.13 More detail: the SELECT trial, GLP-1 and sleep apnea, GLP-1 and fatty liver and semaglutide and kidney disease.

Pill or shot?

As of November 2026 the US has two GLP-1 pills for weight management, the Wegovy pill and Foundayo. Both are daily. The Wegovy pill label calls for an empty stomach and a 30-minute wait before food or drink; the Foundayo label allows it with or without food.13 In their trials, average loss was lower than with the strongest weekly shots, though no trial has compared a pill and a shot directly. There is no tirzepatide pill. See GLP-1 pills.

How do side effects compare?

All of these medicines cause mostly stomach and gut side effects, especially while the dose is being raised. Stopping because of side effects was uncommon in the main trials but more frequent than on placebo:

  • Tirzepatide (SURMOUNT-1): 4.3% to 7.1% stopped due to side effects, vs 2.6% on placebo.1
  • Semaglutide 2.4 mg (STEP 1): 4.5% stopped due to stomach side effects, vs 0.8%.3
  • Semaglutide 7.2 mg (STEP UP): stomach side effects in 70.8% vs 61.2% on 2.4 mg and 42.8% on placebo; skin sensations such as tingling or burning (dysesthesia) in 22.9% vs 6.0% and 0.5%.2
  • Orforglipron (ATTAIN-1): 5.3% to 10.3% stopped due to side effects, vs 2.7%.5

How a person tolerates a medicine often decides which one they can stay on. See GLP-1 nausea and stomach side effects.

What is the best GLP-1 for diabetes?

For blood sugar, the brands are Ozempic, Rybelsus, Ozempic tablets and Mounjaro. In SURPASS-2, 1,879 adults with type 2 diabetes were randomly assigned to tirzepatide (Mounjaro) 5, 10 or 15 mg or semaglutide 1 mg (Ozempic) for 40 weeks. HbA1c fell by 2.01, 2.24 and 2.30 points on tirzepatide vs 1.86 on semaglutide, and weight loss was 1.9 to 5.5 kg greater with tirzepatide.12 Kidney disease can tilt the choice too: Ozempic is the one with a labeled kidney benefit from FLOW.9,13 See GLP-1 weight loss with type 2 diabetes.

Cost and coverage

In practice, insurance coverage and price often decide which GLP-1 a person can get, and they change often. We cover current prices and savings programs in how much Zepbound and Wegovy cost.

This article compares what trials and labels report. It does not tell you which medicine to take. The best option for you depends on your health history, other medicines, how you respond and what you can access. Talk it through with your prescriber.

Common questions

What is the best GLP-1 for weight loss?

By average weight loss in trials, tirzepatide (Zepbound) leads: in the SURMOUNT-5 head-to-head trial of 751 adults with obesity and without diabetes, people lost 20.2% of their weight on tirzepatide vs 13.7% on semaglutide (Wegovy) over 72 weeks. The best choice for a given person also depends on other conditions, side effects, form and coverage, which is a decision for them and their prescriber.

Which GLP-1 causes the most weight loss?

Among approved options, the largest average loss in a main placebo-controlled trial was with tirzepatide 15 mg weekly: 20.9% at 72 weeks in SURMOUNT-1, vs 3.1% on placebo, in adults with obesity or overweight and without diabetes. Semaglutide 7.2 mg weekly led to 18.7% at 72 weeks in STEP UP.

What is the best GLP-1 pill for weight loss?

Two pills are approved for weight management in the US as of November 2026. In separate trials of adults without diabetes, the Wegovy pill (oral semaglutide 25 mg) led to 13.6% average weight loss at 64 weeks in OASIS 4, and orforglipron (Foundayo) to 11.2% at 72 weeks in ATTAIN-1; they have not been compared head to head for weight.

What is the best GLP-1 for diabetes?

In the SURPASS-2 trial of 1,879 adults with type 2 diabetes, tirzepatide (Mounjaro) lowered HbA1c by 2.01 to 2.30 points over 40 weeks vs 1.86 with semaglutide 1 mg (Ozempic). Semaglutide (Ozempic) has a proven kidney benefit in type 2 diabetes with chronic kidney disease from the FLOW trial, so the right choice depends on each person's conditions.

Sources

  1. Jastreboff AM, Aronne LJ, Ahmad NN, et al. Tirzepatide Once Weekly for the Treatment of Obesity (SURMOUNT-1). N Engl J Med. 2022;387(3):205-216. doi:10.1056/NEJMoa2206038 · PubMed
  2. Wharton S, Freitas P, Hjelmesæth J, et al. Once-weekly semaglutide 7·2 mg in adults with obesity (STEP UP): a randomised, controlled, phase 3b trial. Lancet Diabetes Endocrinol. 2025;13(11):949-963. doi:10.1016/S2213-8587(25)00226-8 · PubMed
  3. Wilding JPH, Batterham RL, Calanna S, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP 1). N Engl J Med. 2021;384(11):989-1002. doi:10.1056/NEJMoa2032183 · PubMed
  4. Wharton S, Lingvay I, Bogdanski P, et al. Oral Semaglutide at a Dose of 25 mg in Adults with Overweight or Obesity (OASIS 4). N Engl J Med. 2025;393(11):1077-1087. doi:10.1056/NEJMoa2500969 · PubMed
  5. Wharton S, Aronne LJ, Stefanski A, et al. Orforglipron, an Oral Small-Molecule GLP-1 Receptor Agonist for Obesity Treatment (ATTAIN-1). N Engl J Med. 2025;393(18):1796-1806. doi:10.1056/NEJMoa2511774 · PubMed
  6. Pi-Sunyer X, Astrup A, Fujioka K, et al. A Randomized, Controlled Trial of 3.0 mg of Liraglutide in Weight Management (SCALE Obesity and Prediabetes). N Engl J Med. 2015;373(1):11-22. doi:10.1056/NEJMoa1411892 · PubMed
  7. Aronne LJ, Horn DB, le Roux CW, et al. Tirzepatide as Compared with Semaglutide for the Treatment of Obesity (SURMOUNT-5). N Engl J Med. 2025;393(1):26-36. doi:10.1056/NEJMoa2416394 · PubMed
  8. Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes (SELECT). N Engl J Med. 2023;389(24):2221-2232. doi:10.1056/NEJMoa2307563 · PubMed
  9. Perkovic V, Tuttle KR, Rossing P, et al. Effects of Semaglutide on Chronic Kidney Disease in Patients with Type 2 Diabetes (FLOW). N Engl J Med. 2024;391(2):109-121. doi:10.1056/NEJMoa2403347 · PubMed
  10. Malhotra A, Grunstein RR, Fietze I, et al. Tirzepatide for the Treatment of Obstructive Sleep Apnea and Obesity (SURMOUNT-OSA). N Engl J Med. 2024;391(13):1193-1205. doi:10.1056/NEJMoa2404881 · Full text (PMC)
  11. Sanyal AJ, Newsome PN, Kliers I, et al. Phase 3 Trial of Semaglutide in Metabolic Dysfunction-Associated Steatohepatitis (ESSENCE). N Engl J Med. 2025;392(21):2089-2099. doi:10.1056/NEJMoa2413258 · PubMed
  12. Frías JP, Davies MJ, Rosenstock J, et al. Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes (SURPASS-2). N Engl J Med. 2021;385(6):503-515. doi:10.1056/NEJMoa2107519 · PubMed
  13. US prescribing information on DailyMed: ZEPBOUND, MOUNJARO, WEGOVY injection and tablets, OZEMPIC, RYBELSUS and OZEMPIC tablets, FOUNDAYO, SAXENDA (2026 versions, checked November 2026).
This article summarises published research for general information. It is not medical advice and does not replace advice from your own care team. Never change a medication or dose without talking to your prescriber.

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