Comparisons

Retatrutide vs tirzepatide vs semaglutide: the three-way comparison

Updated by the GLP Ladder Editorial Team. Editorial policy.

Short answer

Semaglutide (GLP-1) and tirzepatide (GIP and GLP-1) are FDA approved; retatrutide (GIP, GLP-1 and glucagon) is investigational as of Oct 19, 2026. Top-dose results, all intention-to-treat-style: semaglutide 2.4 mg −14.9% at 68 weeks, tirzepatide 15 mg −20.9% at 72 weeks, retatrutide 12 mg −25.0% at 80 weeks. Only tirzepatide vs semaglutide is head-to-head: −20.2% vs −13.7% (SURMOUNT-5).

On this page10 sections
  1. Three-way comparison table
  2. How to read the weight numbers
  3. Head-to-head evidence map
  4. Dose ladders
  5. Half-life and accumulation
  6. Side effects
  7. Type 2 diabetes results
  8. Status and outcomes
  9. FAQ
  10. Sources
Key facts (as of Oct 19, 2026)
ItemValueSource
Semaglutide targets and statusGLP-1 receptor; FDA approved (Ozempic 2017, Wegovy 2021)FDA, Oct 19, 2026
Tirzepatide targets and statusGIP and GLP-1 receptors; FDA approved (Mounjaro 2022, Zepbound 2023)Eli Lilly, May 13, 2022
Retatrutide targets and statusGIP, GLP-1 and glucagon receptors; not approved anywhereEli Lilly, Aug 12, 2026
Semaglutide 2.4 mg, STEP 1, week 68−14.9% vs −2.4% placebo (treatment-policy estimand)New England Journal of Medicine, Mar 18, 2021
Tirzepatide 15 mg, SURMOUNT-1, week 72−20.9% vs −3.1% placebo (treatment-regimen estimand)N Engl J Med, Jul 21, 2022
Retatrutide 12 mg, TRIUMPH-1, week 80−25.0% vs −3.9% placebo (treatment-regimen); −28.3% vs −2.2% (efficacy estimand)N Engl J Med, Sep 29, 2026
SURMOUNT-5 head-to-head, week 72Tirzepatide −20.2% vs semaglutide −13.7% (open-label)N Engl J Med, Jul 3, 2025
TRIUMPH-5 head-to-headRetatrutide vs tirzepatide (NCT06662383); active, not recruiting; no resultsClinicalTrials.gov, Jul 20, 2026
Half-livesSemaglutide about 1 week; retatrutide about 6 days; tirzepatide about 5 daysNovo Nordisk, Jun 18, 2026
Retatrutide U.S. submissionPlanned for Q1 2027 (Lilly, Sep 29, 2026)Eli Lilly, Sep 29, 2026

Also useful: Semaglutide overview, GLP-1 level plotter (all compounds), Retatrutide level plotter, Tirzepatide level plotter.

These three weekly peptides form a ladder of receptor targets: semaglutide hits one, tirzepatide two and retatrutide three. Semaglutide and tirzepatide are approved medicines with FDA labels. Retatrutide has finished several Phase 3 trials but is not approved anywhere. The master table below puts the published facts for all three side by side. Each drug has a full hub: retatrutide, tirzepatide and semaglutide.

Three-way comparison table

Retatrutide vs tirzepatide vs semaglutide, published facts as of Oct 19, 2026
ItemSemaglutideTirzepatideRetatrutide
Receptor targetsGLP-1GIP, GLP-1GIP, GLP-1, glucagon
BrandsWegovy, OzempicZepbound, MounjaroNone
StatusFDA approvedFDA approvedInvestigational
First U.S. approvalDec 5, 2017 (Ozempic)May 13, 2022 (Mounjaro)None; submission planned Q1 2027
Half-lifeApproximately 1 weekAbout 5 days (Zepbound label: 5–6)Approximately 6 days
Ladder start0.25 mg (Wegovy label)2.5 mg (label)2 mg (trial protocol)
Top dose2.4 mg; optional 7.2 mg (Wegovy)15 mg12 mg (trials)
Step intervalEvery 4 weeksAt least 4 weeksEvery 4 weeks
Pivotal obesity trialSTEP 1 (n=1,961)SURMOUNT-1 (n=2,539)TRIUMPH-1 (n=2,339)
Timepoint68 weeks72 weeks80 weeks
Top-dose weight change, ITT-style−14.9%−20.9%−25.0%
Placebo, same analysis−2.4%−3.1%−3.9%
Discontinuation for side effects, top dose6.8% vs 3.2% (label)6.2% vs 2.6%11.3% vs 4.9%

Sources: Wegovy label (Novo Nordisk, Jun 18, 2026), Ozempic approval (FDA, Oct 19, 2026), Zepbound label (DailyMed, Aug 28, 2026), Mounjaro approval (Eli Lilly, May 13, 2022), retatrutide half-life (The Lancet, Oct 27, 2022), ladder (Eli Lilly, Dec 11, 2025), STEP 1 (New England Journal of Medicine, Mar 18, 2021), SURMOUNT-1 (N Engl J Med, Jul 21, 2022), TRIUMPH-1 (N Engl J Med, Sep 29, 2026) (Eli Lilly, May 21, 2026), submission plan (Eli Lilly, Sep 29, 2026).

How to read the weight numbers

“ITT-style” here means the analysis counts every randomized participant, whether or not they kept taking the drug. STEP 1 calls this the treatment-policy estimand; SURMOUNT-1 and TRIUMPH-1 call it the treatment-regimen estimand. Lilly’s press releases lead with a different number, the efficacy estimand, which estimates the effect if everyone had stayed on treatment. For retatrutide 12 mg that figure is −28.3% (Eli Lilly, May 21, 2026). Always check which one a headline uses.

Even with matched estimands, this is a cross-trial comparison:

  • The trials ran for 68, 72 and 80 weeks.
  • They were run in different years with different baseline weights. TRIUMPH-1 participants averaged 112.7 kg; SURMOUNT-1 participants averaged 104.8 kg.
  • Side-effect rates come from different kinds of source: label tables pooling several trials for semaglutide and tirzepatide, and one trial’s topline for retatrutide.

The 104-week retatrutide figure of −30.3% that circulates online is an efficacy-estimand result from an extension in a selected group of 532 people (BMI of 35 or more, who completed 80 weeks and tolerated their dose) (Eli Lilly, May 21, 2026). It is not the general 12 mg result.

Head-to-head evidence map

Which pairs have been tested directly
PairTrialPopulationResult
Tirzepatide vs semaglutideSURMOUNT-5751 adults with obesity, no diabetes−20.2% vs −13.7% at 72 weeks (open-label)
Tirzepatide vs semaglutideSURPASS-21,879 adults with type 2 diabetesHbA1c −2.30 (15 mg) vs −1.86 points (1 mg) at 40 weeks
Retatrutide vs tirzepatideTRIUMPH-5 (NCT06662383)Adults with obesityActive, not recruiting; no results
Retatrutide vs semaglutideNCT06260722Type 2 diabetesActive, not recruiting; no results

Sources: (N Engl J Med, Jul 3, 2025) (N Engl J Med, Aug 5, 2021) (ClinicalTrials.gov, Jul 20, 2026)

The SURMOUNT-5 abstract does not name its estimand, so its numbers are shown as least-squares means. TRIUMPH-5’s primary completion was estimated for November 2026 when we checked the registry.

Dose ladders

All three climb in 4-week steps from a low starting dose. For semaglutide and tirzepatide the ladders are the FDA labels; for retatrutide they are trial protocols, reported as published facts and not as recommendations.

Ladders at the earliest allowed pace
WeeksSemaglutide (Wegovy label)Tirzepatide (Zepbound label)Retatrutide (TRIUMPH 12 mg arm)
1–40.25 mg2.5 mg2 mg
5–80.5 mg5 mg4 mg
9–121 mg7.5 mg6 mg
13–161.7 mg10 mg9 mg
17–202.4 mg12.5 mg12 mg
21 onward2.4 mg (optional 7.2 mg)15 mg12 mg

Sources: (Novo Nordisk, Jun 18, 2026) (DailyMed, Aug 28, 2026) (Eli Lilly, Dec 11, 2025)

Milligram doses are not comparable across molecules; each program chose its own scale. Ask your prescriber about any approved-drug dose.

Semaglutide, Wegovy label ladder to 2.4 mg: dose steps and modeled relative amountWeekly doses of 0.25 mg, 0.5 mg, 1 mg, 1.7 mg, 2.4 mg, 4 weeks per step, final step held 12 weeks. Modeled amount peaks at 4.28 mg-equivalents. Model: one-compartment, half-life 7 days.stable window01.252.53.755mg-eq048121620242832weeks from start0.25 mg0.5 mg1 mg1.7 mg2.4 mg
  • Weekly dose (published steps)
  • Modeled amount (mg-eq)
  • Stable window
Wegovy prescribing information: 0.25 → 0.5 → 1 → 1.7 → 2.4 mg, each step 4 weeks. Ladder as published by Novo Nordisk (Jun 18, 2026); curve is a modeled relative amount (t½ 7 days), not plasma concentration. Reported as published, not a recommendation.
Tirzepatide, FDA label ladder to 15 mg: dose steps and modeled relative amountWeekly doses of 2.5 mg, 5 mg, 7.5 mg, 10 mg, 12.5 mg, 15 mg, 4 weeks per step, final step held 8 weeks. Modeled amount peaks at 21.46 mg-equivalents. Model: one-compartment, half-life 5 days.stable window06.2512.518.7525mg-eq048121620242832weeks from start2.5 mg5 mg7.5 mg10 mg12.5 mg15 mg
  • Weekly dose (published steps)
  • Modeled amount (mg-eq)
  • Stable window
Zepbound and Mounjaro prescribing information: 2.5 mg for 4 weeks, then +2.5 mg steps after at least 4 weeks, up to 15 mg. Ladder as published by DailyMed (Aug 28, 2026); curve is a modeled relative amount (t½ 5 days), not plasma concentration. Reported as published, not a recommendation.
Retatrutide, Phase 3 12 mg arm: dose steps and modeled relative amountWeekly doses of 2 mg, 4 mg, 6 mg, 9 mg, 12 mg, 4 weeks per step, final step held 12 weeks. Modeled amount peaks at 19.67 mg-equivalents. Model: one-compartment, half-life 6 days.stable window06.2512.518.7525mg-eq048121620242832weeks from start2 mg4 mg6 mg9 mg12 mg
  • Weekly dose (published steps)
  • Modeled amount (mg-eq)
  • Stable window
TRIUMPH-1 (and TRIUMPH-2/-3/-4, TRANSCEND-T2D-1) 12 mg arm: 2 mg start, stepped every 4 weeks. Ladder as published by Eli Lilly (May 21, 2026); curve is a modeled relative amount (t½ 6 days), not plasma concentration. Reported as published, not a recommendation.

Half-life and accumulation

Model values for once-weekly dosing (GLP Ladder one-compartment model, relative amount)
Model valueSemaglutideTirzepatideRetatrutide
Half-life used7 days5 days6 days
Time to peak used1.5 days1 day1 day
Fraction left after 7 days0.50000.37890.4454
Weekly accumulation ratio2.00001.61011.8033
About 97% of steady stateAbout 35 daysAbout 25 daysAbout 30 days

The model uses a one-compartment Bateman function and reports a relative amount in milligram-equivalents, not a blood concentration. Overlay all three in the multi-compound plotter, or open the retatrutide plotter, tirzepatide plotter and semaglutide plotter one at a time. The retatrutide titration tool and the tirzepatide titration tool date each step.

Side effects

Selected adverse events at the top dose vs placebo (label pools for semaglutide and tirzepatide; TRIUMPH-1 topline for retatrutide)
Adverse eventSemaglutide 2.4 mgTirzepatide 15 mgRetatrutide 12 mg
Nausea44% vs 16%28% vs 8%42.4% vs 14.8%
Diarrhea30% vs 16%23% vs 8%32.0% vs 13.5%
Vomiting24% vs 6%13% vs 2%25.3% vs 4.8%
Constipation24% vs 11%11% vs 5%26.1% vs 10.9%
Dysesthesia2% vs 1%Not in label table12.5% vs 0.9%
Hair loss3% vs 1%5% vs 1%Not in topline

Sources: (Novo Nordisk, Jun 18, 2026) (DailyMed, Aug 28, 2026) (Eli Lilly, May 21, 2026)

Placebo rates differ across sources (nausea 16%, 8% and 14.8%), a sign that the populations and the way events were collected differ too. Dysesthesia, an abnormal skin sensation, is the clearest retatrutide-specific signal; it reached 20.9% on 12 mg in TRIUMPH-4 (Eli Lilly, Dec 11, 2025).

Type 2 diabetes results

Glucose and weight results in type 2 diabetes trials (separate trials)
Drug and doseTrialTimepointHbA1c changeWeight change
Retatrutide 12 mgTRANSCEND-T2D-140 weeks−1.94 points (vs −0.81)−15.3% (vs −2.6%)
Tirzepatide 15 mgSURPASS-240 weeks−2.30 points−11.2 kg (label)
Semaglutide 1 mgSURPASS-240 weeks−1.86 points−5.7 kg (label)

Sources: TRANSCEND-T2D-1, treatment-regimen estimand (The Lancet, Jun 6, 2026); SURPASS-2 (N Engl J Med, Aug 5, 2021) and Mounjaro label (DailyMed, Aug 27, 2026).

TRANSCEND-T2D-1 enrolled people managing diabetes with diet and exercise alone and compared retatrutide with placebo (Eli Lilly, Mar 19, 2026). SURPASS-2 enrolled people on metformin and compared tirzepatide with semaglutide. The populations differ, and weight is reported in different units, so read down the rows within a trial, not across trials.

Status and outcomes

Semaglutide has the longest track record and a proven cardiovascular benefit: in SELECT, major cardiovascular events occurred in 6.5% on semaglutide vs 8.0% on placebo, a hazard ratio of 0.80 (New England Journal of Medicine, Dec 14, 2023). Tirzepatide holds approvals for type 2 diabetes (Eli Lilly, May 13, 2022), weight management (FDA, Nov 8, 2023) and obstructive sleep apnea (FDA, Dec 20, 2024). Retatrutide is investigational: Lilly said on Aug 12, 2026 that no retatrutide medicine has been approved by any regulator (Eli Lilly, Aug 12, 2026), and it is legally available only to people enrolled in Lilly trials. Products sold online as “GLP-3” or research-use retatrutide are not the trial drug; see GLP-3 vs GLP-1.

For the pairwise pages, see retatrutide vs tirzepatide, tirzepatide vs semaglutide and retatrutide vs semaglutide. If you take semaglutide or tirzepatide, talk to your prescriber before acting on any comparison.

Frequently asked questions

Retatrutide vs tirzepatide vs semaglutide: which is strongest?

By average trial weight loss at the top dose, retatrutide reported the most (−25.0% at 80 weeks in TRIUMPH-1), then tirzepatide (−20.9% at 72 weeks in SURMOUNT-1), then semaglutide (−14.9% at 68 weeks in STEP 1), all under intention-to-treat-style estimands. These are separate trials. Only tirzepatide vs semaglutide has been tested head to head, in SURMOUNT-5. Retatrutide is not approved.

Which is FDA approved: retatrutide, tirzepatide or semaglutide?

Semaglutide is approved as Ozempic (Dec 5, 2017) and Wegovy (Jun 4, 2021). Tirzepatide is approved as Mounjaro (May 13, 2022) and Zepbound (Nov 8, 2023). Retatrutide is not approved anywhere; Lilly plans a U.S. submission in the first quarter of 2027, and the drug is legally available only to participants in its clinical trials.

What are the receptor targets of retatrutide, tirzepatide and semaglutide?

Semaglutide acts on the GLP-1 receptor only. Tirzepatide acts on the GIP and GLP-1 receptors. Retatrutide acts on the GIP, GLP-1 and glucagon receptors, which is why it is called a triple agonist and nicknamed GLP-3 online.

Which has the fewest side effects?

All three mainly cause nausea, diarrhea, vomiting and constipation. Top-dose nausea vs placebo was 44% vs 16% for Wegovy 2.4 mg, 28% vs 8% for Zepbound 15 mg (both label pools), and 42.4% vs 14.8% for retatrutide 12 mg in TRIUMPH-1. Discontinuation for side effects was 6.8%, 6.2% and 11.3% respectively. The sources differ, so no clean ranking is possible.

Which has the longest half-life?

Semaglutide, at approximately 1 week per its label. Retatrutide's half-life is approximately 6 days, from a Phase 1b study. Tirzepatide's is about 5 days (5 to 6 days in the Zepbound label). In GLP Ladder's model, the weekly accumulation ratio is 2.0000 for semaglutide, 1.8033 for retatrutide and 1.6101 for tirzepatide.

Are there head-to-head trials between them?

One pair has results: tirzepatide vs semaglutide in SURMOUNT-5 (obesity, −20.2% vs −13.7% at 72 weeks) and SURPASS-2 (type 2 diabetes). Retatrutide vs tirzepatide is being tested in TRIUMPH-5 (NCT06662383), and retatrutide vs semaglutide in a type 2 diabetes trial (NCT06260722). Neither had results as of Oct 19, 2026.

Sources

  1. Once-Weekly Semaglutide in Adults with Overweight or Obesity. New England Journal of Medicine (Wilding JPH et al.; PMID 33567185), Mar 18, 2021. Accessed Oct 19, 2026.
  2. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med 2022;387(3):205-216 (Jastreboff AM et al.; PubMed PMID 35658024; doi:10.1056/NEJMoa2206038), Jul 21, 2022. Accessed Oct 19, 2026.
  3. Tirzepatide as Compared with Semaglutide for the Treatment of Obesity. N Engl J Med 2025;393(1):26-36 (Aronne LJ et al.; PubMed PMID 40353578; doi:10.1056/NEJMoa2416394), Jul 3, 2025. Accessed Oct 19, 2026.
  4. Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes. N Engl J Med 2021;385(6):503-515 (Frías JP et al.; PubMed PMID 34170647; doi:10.1056/NEJMoa2107519), Aug 5, 2021. Accessed Oct 19, 2026.
  5. Retatrutide, a Triple Hormone Receptor Agonist, for Treatment of Obesity. N Engl J Med (abstract via PubMed PMID 42814954; doi:10.1056/NEJMoa2604169), Sep 29, 2026. Accessed Oct 19, 2026.
  6. Lilly's triple agonist, retatrutide, delivered powerful weight loss in pivotal Phase 3 obesity trial. Eli Lilly and Company (via PR Newswire; also investor.lilly.com), May 21, 2026. Accessed Oct 19, 2026.
  7. Lilly's triple agonist, retatrutide, delivered weight loss of up to an average of 71.2 lbs along with substantial relief from osteoarthritis pain in first successful Phase 3 trial. Eli Lilly and Company (via PR Newswire), Dec 11, 2025. Accessed Oct 19, 2026.
  8. Lilly's triple agonist, retatrutide, demonstrated significant reductions in A1C and weight in first Phase 3 trial for treatment of type 2 diabetes. Eli Lilly and Company (via PR Newswire), Mar 19, 2026. Accessed Oct 19, 2026.
  9. Efficacy and safety of retatrutide, a GIP, GLP-1, and glucagon receptor agonist, in people with type 2 diabetes and inadequate glycaemic control with diet and exercise (TRANSCEND-T2D-1): a double-blind, randomised, phase 3 trial. The Lancet (published online Jun 6, 2026; issue Jun 13, 2026; 407(10546):2402-2413; abstract via PubMed PMID 42250575; doi:10.1016/S0140-6736(26)00967-0), Jun 6, 2026. Accessed Oct 19, 2026.
  10. Lilly's triple agonist, retatrutide, delivered substantial weight loss and A1C reduction, underscoring its potential promise for people with obesity and type 2 diabetes. Eli Lilly and Company (via PR Newswire; also investor.lilly.com), Sep 29, 2026. Accessed Oct 19, 2026.
  11. Lilly calls on online platforms, payment companies and regulators to shut down the illegal retatrutide black market. Eli Lilly and Company (via PR Newswire), Aug 12, 2026. Accessed Oct 19, 2026.
  12. LY3437943, a novel triple GIP, GLP-1, and glucagon receptor agonist in people with type 2 diabetes: a phase 1b, multicentre, double-blind, placebo-controlled, randomised, multiple-ascending dose trial. The Lancet 2022;400(10366):1869-1881 (abstract via PubMed PMID 36354040; doi:10.1016/S0140-6736(22)02033-5), Oct 27, 2022. Accessed Oct 19, 2026.
  13. LY3437943, a novel triple glucagon, GIP, and GLP-1 receptor agonist for glycemic control and weight loss: From discovery to clinical proof of concept. Cell Metabolism 2022;34(9):1234-1247.e9 (abstract via PubMed PMID 35985340; doi:10.1016/j.cmet.2022.07.013), Aug 18, 2022. Accessed Oct 19, 2026.
  14. A Study of Retatrutide (LY3437943) Compared to Tirzepatide (LY3298176) in Adults Who Have Obesity (TRIUMPH-5). ClinicalTrials.gov (U.S. NLM), Jul 20, 2026. Accessed Oct 19, 2026.
  15. FDA approves Lilly's Mounjaro™ (tirzepatide) injection, the first and only GIP and GLP-1 receptor agonist for the treatment of adults with type 2 diabetes. Eli Lilly and Company (investor.lilly.com), May 13, 2022. Accessed Oct 19, 2026.
  16. FDA Approves New Medication for Chronic Weight Management. U.S. Food and Drug Administration, Nov 8, 2023. Accessed Oct 19, 2026.
  17. FDA Approves First Medication for Obstructive Sleep Apnea. U.S. Food and Drug Administration, Dec 20, 2024. Accessed Oct 19, 2026.
  18. ZEPBOUND (tirzepatide) injection, for subcutaneous use - Full Prescribing Information, Medication Guide and Instructions for Use (DailyMed SPL set ID 487cd7e7-434c-4925-99fa-aa80b1cc776b, version 40). U.S. National Library of Medicine (DailyMed) / Eli Lilly and Company, Aug 28, 2026. Accessed Oct 19, 2026.
  19. MOUNJARO (tirzepatide) injection, for subcutaneous use - Full Prescribing Information, Medication Guide and Instructions for Use (DailyMed SPL set ID d2d7da5d-ad07-4228-955f-cf7e355c8cc0, version 40). U.S. National Library of Medicine (DailyMed) / Eli Lilly and Company, Aug 27, 2026. Accessed Oct 19, 2026.
  20. WEGOVY (semaglutide) injection, for subcutaneous use; WEGOVY (semaglutide) tablets, for oral use - Full Prescribing Information (SPL, Revised 6/2026). Novo Nordisk / National Library of Medicine DailyMed, Jun 18, 2026. Accessed Oct 19, 2026.
  21. Drugs@FDA record NDA215256 (WEGOVY semaglutide injection) - submissions history. U.S. Food and Drug Administration (openFDA Drugs@FDA API), Oct 19, 2026. Accessed Oct 19, 2026.
  22. Drugs@FDA record NDA209637 (OZEMPIC semaglutide injection) - submissions history. U.S. Food and Drug Administration (openFDA Drugs@FDA API), Oct 19, 2026. Accessed Oct 19, 2026.
  23. Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes. New England Journal of Medicine (Lincoff AM et al.; PMID 37952131), Dec 14, 2023. Accessed Oct 19, 2026.

Guides and data