Which GLP-1 has the most weight loss in clinical trials?

Tirzepatide (Zepbound) has the highest in the approved class — about 20.9% at the top dose over 72 weeks in SURMOUNT-1, and it beat semaglutide head-to-head in SURMOUNT-5 (−20.2% vs −13.7%). Semaglutide (Wegovy) is about 14.9% in STEP 1; oral orforglipron is about 11%. Investigational drugs like retatrutide (phase 2 ~24%) may go higher but are not yet approved — see our pipeline tracker.

What is the difference between the STEP and SURMOUNT trials?

STEP is the semaglutide (Wegovy) obesity trial program; SURMOUNT is the tirzepatide (Zepbound) obesity program. They are run by different companies (Novo Nordisk vs Eli Lilly) in similar but not identical populations, so the numbers are broadly but not exactly comparable — only the SURMOUNT-5 head-to-head compares the two drugs directly.

Are the weight-loss percentages comparable across these trials?

Only loosely. Populations, doses, durations, and statistical methods differ, and only the three head-to-head trials (STEP 8, SURMOUNT-5, SURPASS-2) compare two drugs directly. Treat the table as a map of the evidence, not a strict leaderboard.

Which GLP-1 trials show heart, kidney, or liver benefit?

Semaglutide: SELECT (20% fewer cardiovascular events), FLOW (24% slower kidney-disease progression), ESSENCE (MASH resolution), STEP-HFpEF (heart-failure symptoms). Tirzepatide: SUMMIT (heart failure), SURMOUNT-OSA (sleep apnea), SYNERGY-NASH (MASH, phase 2). These are the trials behind the drugs' expanding, non-weight-loss FDA indications.

GLP-1 Trial Results Database: STEP, SURMOUNT & More

At a glance

27 major trials, every number sourcedWeight loss and outcome results from the pivotal STEP, SURMOUNT, SELECT, FLOW, ESSENCE, SURMOUNT-OSA, ATTAIN, and SCALE trials — each verified against its PubMed record

The single sourced table of the major approved-drug GLP-1 trials — STEP, SURMOUNT, SELECT, FLOW, ESSENCE, SURMOUNT-OSA, ATTAIN, SCALE: 27 trials, every number verified against its PubMed record.
On weight, tirzepatide leads (SURMOUNT-1 ~20.9%; it beat semaglutide head-to-head in SURMOUNT-5, −20.2% vs −13.7%); semaglutide ~14.9% (STEP 1); oral orforglipron ~11%.
The organ-outcome trials are now the strongest part of the class: SELECT (heart), FLOW (kidney), ESSENCE (liver/MASH), SURMOUNT-OSA (sleep apnea), SUMMIT (heart failure).
Cross-trial comparisons are unreliable by design (different populations, doses, durations, estimands); only STEP 8, SURMOUNT-5, and SURPASS-2 compare two drugs directly.

This is the single reference table for the major GLP-1 and incretin clinical trials — the pivotal weight-loss trials plus the organ-outcome trials (heart, kidney, liver, sleep apnea, knee) for the FDA-approved drugs: semaglutide (Wegovy, Ozempic, Rybelsus), tirzepatide (Zepbound, Mounjaro), orforglipron (Foundayo), and liraglutide (Saxenda). Every row is sourced to its primary peer-reviewed publication, listed in the References. Investigational drugs (retatrutide, CagriSema, MariTide, survodutide) are tracked separately on our GLP-1 pipeline tracker. Read the caveats below before comparing numbers across trials.

How to read this database

Do not rank drugs by these numbers alone. Trials differ in population, dose, duration, and statistical estimand. Only head-to-head trials (STEP 8, SURMOUNT-5, SURPASS-2) compare two drugs directly.
Estimand matters. We report each trial's headline (treatment-policy / intention-to-treat) figure for comparability; the "efficacy estimand" (on-treatment) figure a trial also reports is usually a point or two higher. Individual deep-dives may cite the efficacy estimand.
Withdrawal-design trials read differently. STEP 4, SURMOUNT-3, and SURMOUNT-4 randomize people who already lost weight to continue the drug or switch to placebo — so the result is "continued loss vs weight regained," not a simple placebo-subtracted number.
Some results are interim or earlier-phase. ESSENCE is a pre-planned 72-week interim of an ongoing trial; SYNERGY-NASH is a phase 2 study. Both are flagged in the table.
Dose and brand nuances are preserved. FLOW used the 1.0 mg (Ozempic) dose, not the 2.4 mg obesity dose; SELECT's "20%" is a relative risk reduction (hazard ratio 0.80), not 20 percentage points.

Semaglutide (Wegovy / Ozempic / Rybelsus) — weight-loss trials

Semaglutide pivotal weight-loss trials. Weight loss = top dose vs placebo unless a head-to-head. Sourced to the References.

Trial	Population	N	Duration	Weight loss (top dose vs placebo)	Year
STEP 1	Obesity, no diabetes	1,961	68 wk	−14.9% vs −2.4%	2021
STEP 2	Overweight/obesity + type 2 diabetes	1,210	68 wk	−9.6% vs −3.4%	2021
STEP 3	Obesity + intensive behavioral therapy	611	68 wk	−16.0% vs −5.7%	2021
STEP 4	Obesity; withdrawal after 20-wk run-in	803	68 wk	Continued −7.9% vs +6.9% regained	2021
STEP 5	Obesity, no diabetes (2-year)	304	104 wk	−15.2% vs −2.6%	2022
STEP 8	Obesity; semaglutide vs liraglutide	338	68 wk	Sema −15.8% vs lira −6.4%	2022
OASIS 1 (oral sema 50 mg)	Obesity, no diabetes	667	68 wk	−15.1% vs −2.4%	2023

The STEP program is the backbone of semaglutide's obesity approval — see our week-by-week results timeline, and compare vetted semaglutide providers. STEP 4^[4] is the key "what happens when you stop" trial: people regained about 7% after switching to placebo.

Tirzepatide (Zepbound / Mounjaro) — weight-loss trials

Tirzepatide pivotal weight-loss trials. Weight loss = top 15 mg dose vs placebo unless a head-to-head. Sourced to the References.

Trial	Population	N	Duration	Weight loss (top dose vs placebo)	Year
SURMOUNT-1	Obesity, no diabetes	2,539	72 wk	−20.9% vs −3.1%	2022
SURMOUNT-2	Obesity + type 2 diabetes	938	72 wk	−14.7% vs −3.2%	2023
SURMOUNT-3	Obesity; after 12-wk lifestyle lead-in	579	72 wk	Additional −18.4% vs +2.5% regained	2023
SURMOUNT-4	Obesity; withdrawal after 36-wk lead-in	670	wk 36→88	Continued −5.5% vs +14.0% regained (total −25.3%)	2024
SURMOUNT-5	Obesity; tirzepatide vs semaglutide	751	72 wk	Tirz −20.2% vs sema −13.7%	2025

SURMOUNT-5^[12] is the direct head-to-head: tirzepatide beat semaglutide (−20.2% vs −13.7%) — full head-to-head breakdown, tirzepatide results timeline, and vetted tirzepatide providers.

Oral orforglipron & liraglutide — weight-loss trials

Orforglipron (the first no-restriction oral GLP-1) and liraglutide. Sourced to the References.

Trial	Drug	Population	N	Duration	Weight loss (top dose vs placebo)	Year
ATTAIN-1	Orforglipron (Foundayo), oral	Obesity, no diabetes	3,127	72 wk	−11.2% (36 mg) vs −2.1%	2025
ATTAIN-2	Orforglipron (Foundayo), oral	Obesity + type 2 diabetes	1,613	72 wk	−9.6% (36 mg) vs −2.5%	2025
SCALE	Liraglutide 3.0 mg (Saxenda)	Obesity ± prediabetes	3,731	56 wk	−8.0% vs −2.6%	2015

Orforglipron (Foundayo) is the first oral GLP-1 with no food-or-water timing rules — the ATTAIN obesity evidence, its FDA approval, and oral-GLP-1 providers. Liraglutide (SCALE) is the older daily injectable it and the weekly drugs now outperform.

Organ-outcome & indication trials (heart, kidney, liver, sleep apnea, knee, diabetes)

The trials behind GLP-1s' non-weight-loss indications and outcomes. Primary endpoint result shown. Sourced to the References.

Trial	Drug	Indication	N	Duration	Primary result	Year
SELECT	Semaglutide 2.4 mg	CVD, no diabetes	17,604	~3.3 yr	3-pt MACE HR 0.80 (20% risk reduction), 6.5% vs 8.0%	2023
SURPASS-2	Tirzepatide vs sema 1 mg	Type 2 diabetes	1,879	40 wk	HbA1c −2.30 vs −1.86 (superior); −5.5 kg more weight	2021
FLOW	Semaglutide 1.0 mg	Type 2 diabetes + CKD	3,533	3.4 yr	Kidney composite HR 0.76 (24% reduction)	2024
ESSENCE	Semaglutide 2.4 mg	MASH (fibrosis F2–F3)	800 (interim)	72-wk interim	MASH resolution 62.9% vs 34.3%	2025
SYNERGY-NASH (phase 2)	Tirzepatide	MASH (fibrosis F2–F3)	190	52 wk	MASH resolution 62% (15 mg) vs 10%	2024
STEP-HFpEF	Semaglutide 2.4 mg	Heart failure (HFpEF) + obesity	529	52 wk	KCCQ symptom score +16.6 vs +8.7; weight −13.3%	2023
SUMMIT	Tirzepatide	Heart failure (HFpEF) + obesity	731	~104 wk	CV death / worsening HF HR 0.62, 9.9% vs 15.3%	2025
SURMOUNT-OSA	Tirzepatide	Moderate–severe sleep apnea + obesity	469	52 wk	AHI −25.3 / −29.3 events/hr vs placebo	2024
STEP 9	Semaglutide 2.4 mg	Obesity + knee osteoarthritis	407	68 wk	WOMAC pain −41.7 vs −27.5; weight −13.7%	2024
SUSTAIN-6	Semaglutide s.c.	Type 2 diabetes, high CV risk	3,297	104 wk	MACE HR 0.74 (superiority)	2016
PIONEER 6	Oral semaglutide	Type 2 diabetes, high CV risk	3,183	~16 mo	MACE HR 0.79 (noninferior)	2019
ACHIEVE-1	Orforglipron (oral)	Early type 2 diabetes	559	40 wk	HbA1c −1.48 vs −0.41; weight −7.6%	2025

What the trials actually show

On weight, tirzepatide leads. SURMOUNT-1^[8] delivered ~20.9% and the head-to-head SURMOUNT-5^[12] confirmed it beats semaglutide (STEP 1^[1], ~14.9%). Oral orforglipron (~11%) trades some magnitude for pill convenience. Beyond weight, the organ story is now the strongest part of the class: semaglutide cut cardiovascular events in SELECT^[16], slowed kidney disease in FLOW^[18], resolved MASH in ESSENCE^[19], and tirzepatide treats obstructive sleep apnea and heart failure. The withdrawal trials (STEP 4^[4], SURMOUNT-4) are the honest warning: stop the drug and much of the weight comes back — see what the trials show on side effects, and the pipeline and latest quarterly readouts for what is coming next.

How we built and verified this database. Every trial's headline number was cross-checked against the primary publication's abstract, and all 27 PubMed IDs were verified live via NCBI esummary (title, journal, and year confirmed) — no PMID is hand-cited or constructed. Verified July 2026. Cross-trial comparisons remain unreliable by design; use the References to read any trial in full.

Frequently Asked Questions

References

1.Wilding JPH, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP 1). N Engl J Med. 2021. PMID: 33567185.
2.Davies M, et al. Semaglutide 2.4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2). Lancet. 2021. PMID: 33667417.
3.Wadden TA, et al. Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy (STEP 3). JAMA. 2021. PMID: 33625476.
4.Rubino D, et al. Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance (STEP 4). JAMA. 2021. PMID: 33755728.
5.Garvey WT, et al. Two-year effects of semaglutide in adults with overweight or obesity (STEP 5). Nat Med. 2022. PMID: 36216945.
6.Rubino DM, et al. Effect of Weekly Subcutaneous Semaglutide vs Daily Liraglutide on Body Weight (STEP 8). JAMA. 2022. PMID: 35015037.
7.Knop FK, et al. Oral semaglutide 50 mg once per day in adults with overweight or obesity (OASIS 1). Lancet. 2023. PMID: 37385278.
8.Jastreboff AM, et al. Tirzepatide Once Weekly for the Treatment of Obesity (SURMOUNT-1). N Engl J Med. 2022. PMID: 35658024.
9.Garvey WT, et al. Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2). Lancet. 2023. PMID: 37385275.
10.Wadden TA, et al. Tirzepatide after intensive lifestyle intervention in adults with overweight or obesity (SURMOUNT-3). Nat Med. 2023. PMID: 37840095.
11.Aronne LJ, et al. Continued Treatment With Tirzepatide for Maintenance of Weight Reduction (SURMOUNT-4). JAMA. 2024. PMID: 38078870.
12.Aronne LJ, et al. Tirzepatide as Compared with Semaglutide for the Treatment of Obesity (SURMOUNT-5). N Engl J Med. 2025. PMID: 40353578.
13.Wharton S, et al. Orforglipron, an Oral Small-Molecule GLP-1 Receptor Agonist for Obesity Treatment (ATTAIN-1). N Engl J Med. 2025. PMID: 40960239.
14.Horn DB, et al. Orforglipron for obesity in people with type 2 diabetes (ATTAIN-2). Lancet. 2026. PMID: 41275875.
15.Pi-Sunyer X, et al. A Randomized, Controlled Trial of 3.0 mg of Liraglutide in Weight Management (SCALE). N Engl J Med. 2015. PMID: 26132939.
16.Lincoff AM, et al. Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes (SELECT). N Engl J Med. 2023. PMID: 37952131.
17.Frías JP, et al. Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes (SURPASS-2). N Engl J Med. 2021. PMID: 34170647.
18.Perkovic V, et al. Effects of Semaglutide on Chronic Kidney Disease in Patients with Type 2 Diabetes (FLOW). N Engl J Med. 2024. PMID: 38785209.
19.Sanyal AJ, et al. Phase 3 Trial of Semaglutide in Metabolic Dysfunction-Associated Steatohepatitis (ESSENCE). N Engl J Med. 2025. PMID: 40305708.
20.Loomba R, et al. Tirzepatide for MASH with Liver Fibrosis (SYNERGY-NASH, phase 2). N Engl J Med. 2024. PMID: 38856224.
21.Kosiborod MN, et al. Semaglutide in Patients with Heart Failure with Preserved Ejection Fraction and Obesity (STEP-HFpEF). N Engl J Med. 2023. PMID: 37622681.
22.Packer M, et al. Tirzepatide for Heart Failure with Preserved Ejection Fraction and Obesity (SUMMIT). N Engl J Med. 2025. PMID: 39555826.
23.Malhotra A, et al. Tirzepatide for the Treatment of Obstructive Sleep Apnea and Obesity (SURMOUNT-OSA). N Engl J Med. 2024. PMID: 38912654.
24.Bliddal H, et al. Once-Weekly Semaglutide in Persons with Obesity and Knee Osteoarthritis (STEP 9). N Engl J Med. 2024. PMID: 39476339.
25.Marso SP, et al. Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes (SUSTAIN-6). N Engl J Med. 2016. PMID: 27633186.
26.Husain M, et al. Oral Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes (PIONEER 6). N Engl J Med. 2019. PMID: 31185157.
27.Rosenstock J, et al. Orforglipron, an Oral Small-Molecule GLP-1 Receptor Agonist, in Early Type 2 Diabetes (ACHIEVE-1). N Engl J Med. 2025. PMID: 40544435.

FLOW Trial: Semaglutide Kidney Subgroup Detail (2026)

A deep dive into the FLOW trial secondary analyses: eGFR slope, cardiovascular and all-cause death, heart failure, and benefit across CKD severity, SGLT2i, and MRA subgroups.

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GLP-1 After Hepatitis C Cure (SVR): Metabolic Syndrome Reversal

Hepatitis C SVR patients commonly develop new metabolic syndrome + obesity within 5 years. GLP-1 receptor agonists are safe + effective in this population. We review the published cohort data, the MASH overlap, and the hepatology pathway.

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Retatrutide vs Wegovy: cross-trial weight-loss + safety evidence (2026)

Retatrutide (investigational) -28.3% TBWL at 12 mg / 80 wk in TRIUMPH-1 vs Wegovy (FDA-approved 2021) -14.9% at 68 wk in STEP-1 — about 1.9x the magnitude on a cross-trial basis. No head-to-head RCT. Wegovy has SELECT (20% MACE reduction); retatrutide TRIUMPH-3 CVOT pending.

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Wegovy Constipation: STEP-1 Rates, Mechanism & Evidence-Based Relief Protocol

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GLP-1 Weight-Loss Trial Results: The Complete Database (STEP, SURMOUNT & Every Major Trial)

How to read this database

Semaglutide (Wegovy / Ozempic / Rybelsus) — weight-loss trials

Tirzepatide (Zepbound / Mounjaro) — weight-loss trials

Oral orforglipron & liraglutide — weight-loss trials

Organ-outcome & indication trials (heart, kidney, liver, sleep apnea, knee, diabetes)

What the trials actually show

Frequently Asked Questions

References

Where to get tirzepatide (Mounjaro / Zepbound): vetted providers

Breeze Meds

Enhance MD

Embody

How to read this database

Semaglutide (Wegovy / Ozempic / Rybelsus) — weight-loss trials

Tirzepatide (Zepbound / Mounjaro) — weight-loss trials

Oral orforglipron & liraglutide — weight-loss trials

Organ-outcome & indication trials (heart, kidney, liver, sleep apnea, knee, diabetes)

What the trials actually show

Frequently Asked Questions

References

Related research

Where to get tirzepatide (Mounjaro / Zepbound): vetted providers

Breeze Meds

Enhance MD

Embody