GLP-1 Comparison Chart: Every Agonist, One Consistent Analysis

By Evan Marsh, EditorUpdated August 7, 2026Trial data matched estimand for estimand

Most comparisons of these drugs are wrong in the same specific way, and it is not a matter of opinion. Obesity trials publish every result twice — once counting all randomized participants and once assuming everyone stayed on the drug — and the three main sponsors use six different names for those two analyses. Take the flattering number for one drug and the conservative number for another and you have manufactured a difference that does not exist. This table shows both conventions for every compound that reports both.

The comparison

Compound	Receptor targets	Pivotal trial	Duration	Counting everyone randomized	Assuming full adherence	Status
Retatrutide	GIP + GLP-1 + glucagon	TRIUMPH-1 (n=2,339)	80 weeks	−25.0%	−28.3%	Phase 3, not approved
Tirzepatide	GIP + GLP-1	SURMOUNT-1 (n=2,539)	72 weeks	−20.9%	Reported separately	Approved (Zepbound, Mounjaro)
CagriSema	Amylin + GLP-1	REDEFINE 1 (n=3,417)	68 weeks	−20.4%	Reported separately	Phase 3, not approved
Semaglutide	GLP-1	STEP-1 (n=1,961)	68 weeks	−14.9%	Reported separately	Approved (Wegovy, Ozempic)
Survodutide	Glucagon + GLP-1	SYNCHRONIZE-1 (n=725)	76 weeks	−13.0%	Reported separately	Phase 3, not approved

Mean body-weight reduction, every bar counting all randomised participants

InvestigationalFDA approved

RetatrutideTRIUMPH-1, 80 weeks

25.0%

TirzepatideSURMOUNT-1, 72 weeks

20.9%

CagriSemaREDEFINE 1, 68 weeks

20.4%

SemaglutideSTEP-1, 68 weeks

14.9%

SurvodutideSYNCHRONIZE-1, 76 weeks

13.0%

The naming problem, in one place. "Counting everyone randomized" is Lilly's treatment-regimen estimand and Novo Nordisk's treatment policyestimand. "Assuming full adherence" is Lilly's efficacy estimand and Novo'strial product estimand — sometimes written as if-all-adhered. Same two analyses, six names. Every figure in the bold column above uses the first convention, which is why retatrutide appears at 25.0% here rather than the 28.3% or 30.3% quoted elsewhere.

What the table still cannot tell you

Trial durations differ — 68 to 80 weeks. Weight curves in several of these programs were still descending at the end, so longer trials flatter their drug for reasons unrelated to the molecule.
Populations differ. Separate trials, separate enrollment criteria, separate eras. Cross-trial comparison is an estimate, not a measurement.
Evidence tiers differ. STEP-1, SURMOUNT-1, REDEFINE 1 and SYNCHRONIZE-1 are peer-reviewed publications. The retatrutide Phase 3 figures are company topline announcements, which is weaker evidence and can change on the way to publication.
Almost no head-to-head data exists. The one exception in this group is REDEFINE 4, where CagriSema was compared directly against tirzepatide — a trial CagriSema lost, and whose non-inferiority margin was not disclosed.

Weight is not the only axis

Ranking this class on the scale alone hides the thing most likely to matter clinically:

Compound	Hard outcome evidence	Other approved indications
Semaglutide	Reduces major adverse cardiovascular events	Type 2 diabetes; noncirrhotic MASH with fibrosis
Tirzepatide	Approved for obstructive sleep apnea in adults with obesity	Type 2 diabetes
Retatrutide	None	None — sleep apnea and knee osteoarthritis studied but not approved
CagriSema	None	None
Survodutide	None	None

Read the two tables together and the ordering reverses depending on the question. Largest weight reduction: retatrutide. Largest among drugs a person can actually be prescribed: tirzepatide. Only compound proven to reduce heart attacks and strokes: semaglutide. All three statements are accurate simultaneously.

What happens after stopping

One finding applies across the class and deserves more attention than the rankings. The STEP-1 trial extension followed participants after semaglutide withdrawal and documented substantial weight regain. Nothing suggests the newer compounds behave differently, and for retatrutide no discontinuation data has been published at all. These are treatments for a chronic condition, not courses with an endpoint.

Frequently asked questions

Which GLP-1 drug produces the most weight loss?

Retatrutide reported the largest reduction — 25.0% at 80 weeks counting every randomized participant — but it is investigational and not approved. Among approved drugs, tirzepatide leads at 20.9% over 72 weeks.

Why do the same drugs show different numbers on different sites?

Because every obesity trial reports two results: one counting all randomized participants and one assuming full adherence. Sponsors use six different names for those two analyses. The gap runs 1.6 to 3.6 percentage points — larger than the difference between some neighbouring drugs. Sites that mix conventions produce rankings that are simply wrong.

Are these numbers directly comparable?

Only approximately. Every drug in this table was tested in a separate trial, in a different population, over a different duration, in a different era. Matching the analysis convention removes the largest source of error, but trial length still varies from 68 to 80 weeks and no head-to-head trial exists between most of these compounds.

Which one is best?

It depends what "best" measures. On weight, retatrutide. On weight among prescribable drugs, tirzepatide. On demonstrated cardiovascular outcomes, semaglutide is the only one with that evidence. Ranking on weight alone hides that distinction.

Which of these can a doctor prescribe?

Semaglutide and tirzepatide are FDA approved. CagriSema, survodutide and retatrutide are investigational — no prescription pathway and no legal compounding route.

Sources

Jastreboff AM et al. Triple–Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial. New England Journal of Medicine, 2023;389(6):514–526. PubMed
Jastreboff AM et al. Tirzepatide Once Weekly for the Treatment of Obesity (SURMOUNT-1). New England Journal of Medicine, 2022;387(3):205–216. PubMed
Wilding JPH et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP-1). New England Journal of Medicine, 2021;384(11):989–1002. PubMed
Garvey WT et al. Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity (REDEFINE 1). New England Journal of Medicine, 2025;393(7):635–647. PubMed
le Roux CW et al. Survodutide Once Weekly for the Treatment of Adults with Obesity (SYNCHRONIZE-1). New England Journal of Medicine, published online 7 June 2026. PubMed · doi:10.1056/NEJMoa2600751
Novo Nordisk. REDEFINE 4 head-to-head results versus tirzepatide, February 2026. Company announcement · NCT06131437. Not peer-reviewed; non-inferiority margin not disclosed.
Eli Lilly. TRIUMPH-1 topline results, 21 May 2026. Company announcement. Not peer-reviewed.
Wilding JPH et al. Weight regain after withdrawal of semaglutide: the STEP 1 trial extension. Diabetes, Obesity and Metabolism, 2022;24(8):1553–1564. PubMed
Labels: Wegovy (semaglutide) · Zepbound (tirzepatide)

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Not medical advice. Semaglutide and tirzepatide are approved prescription medicines; decisions about them belong with a licensed physician. Retatrutide, CagriSema and survodutide are investigational and not approved for human use.