There is no head-to-head trial of petrelintide against semaglutide or tirzepatide, so any claim that one “beats” another is a guess. This page puts the published numbers side by side, shows why they cannot simply be compared, and says what the one relevant head-to-head result does show.
Ask PeptideBlog about any peptide
Quick answer: Petrelintide is an amylin analogue, while semaglutide targets the GLP-1 receptor and tirzepatide targets the GIP and GLP-1 receptors.[2][6][7] In separate trials, semaglutide 2.4 mg produced 14.9% mean weight loss at 68 weeks, tirzepatide up to 20.9% at 72 weeks, and petrelintide 7.9% to 9.8% at week 28 (up to 10.7% by week 42).[6][7][1][4] The trials differ in length, population and analysis method, so the figures are not a ranking.
People searching “petrelintide vs semaglutide” or “petrelintide vs tirzepatide” want to know whether the newer drug is stronger or gentler. The honest answer starts with what the evidence can and cannot support. For each drug there is a separate research entry on this site: semaglutide, tirzepatide and petrelintide. This page does not tell any reader what to take, and the numbers below describe trial participants, not individual outcomes.
Three different mechanisms
Semaglutide and tirzepatide belong to the incretin family, hormones released by the gut after eating. Petrelintide belongs to a different family. Amylin is a hormone made alongside insulin that helps signal fullness. Petrelintide is a long-acting version of it.
Swipe the table sideways to see every column.
| Drug | Type | Receptors it acts on | Maker |
|---|---|---|---|
| Petrelintide | Amylin analogue, once weekly | Amylin receptors (AMY1 and AMY3) and the calcitonin receptor[2] | Zealand Pharma with Roche |
| Semaglutide (2.4 mg weekly) | GLP-1 receptor agonist[6] | GLP-1 receptor | Novo Nordisk |
| Tirzepatide | Dual GIP and GLP-1 receptor agonist[7] | GIP receptor and GLP-1 receptor | Eli Lilly |
Because amylin works through different receptors, the working idea is that it might add to an incretin drug rather than copy it. That idea is being tested in combination trials, covered below. For how petrelintide differs from the other amylin drugs, see the amylin drug comparison.
Approval status
Semaglutide 2.4 mg was approved by the FDA for chronic weight management on 4 June 2021.[8] Tirzepatide was approved for the same purpose on 8 November 2023 under the brand name Zepbound.[9] Petrelintide is not approved anywhere and is in Phase 3. The approval timeline guide explains what the registry dates imply.
The weight-loss numbers
These are the headline results from the main trial of each drug. All three trials enrolled adults with obesity or overweight and no type 2 diabetes, and compared the drug with placebo.
Swipe the table sideways to see every column.
| Trial | Drug and amounts studied | Length | Mean weight change, drug | Mean weight change, placebo | Analysis method |
|---|---|---|---|---|---|
| STEP 1 (2021)[6] | Semaglutide 2.4 mg weekly; 1,961 adults | 68 weeks | 14.9% loss | 2.4% loss | Regardless of whether treatment continued |
| SURMOUNT-1 (2022)[7] | Tirzepatide 5, 10 or 15 mg weekly; 2,539 adults | 72 weeks | 15.0%, 19.5% and 20.9% loss | 3.1% loss | Treatment-regimen estimand |
| ZUPREME-1 (2026)[1][4] | Petrelintide, five arms from 1.0 to 9.0 mg weekly; 485 treated | 42 weeks (main endpoint at week 28) | 7.9% to 9.8% loss at week 28; up to 10.7% by week 42 | 1.7% loss at week 28 | Efficacy estimand (people who stayed on treatment) |
Evidence category: published human clinical trials (Tier 1), each funded by the drug’s maker. The 10.7% week 42 figure is the maximum reported in the paper and in the sponsor’s announcement; it is not an average across arms.
Why you cannot read down the column
A tempting conclusion is that petrelintide loses about half as much weight as the incretin drugs. The table does not support that, for four reasons.
- Time. STEP 1 ran 68 weeks and SURMOUNT-1 ran 72. The main petrelintide endpoint was at week 28, and weight was still falling at week 42 (up to 10.7%).[1][4] Nobody knows where it levels off, and the Phase 3 trials use a week 64 endpoint to answer that.
- Analysis method. The petrelintide figures use the efficacy estimand, which counts people while they stay on treatment. STEP 1’s figure counts everyone as randomized, whether or not they continued, and SURMOUNT-1’s headline uses a treatment-regimen estimand. An efficacy estimand usually gives a larger number than a treatment-regimen one for the same drug. This page uses each figure only with the label its source gives it.[6][7][4]
- Who was enrolled. SURMOUNT-1 participants averaged 104.8 kg with a BMI of 38.0.[7] ZUPREME-1 participants averaged 107.1 kg with a BMI of 36.7.[1] Different starting points change how percentages should be read.
- Placebo. Placebo arms lost 1.7%, 2.4% and 3.1%, which reflects different lifestyle support and follow-up in each trial.
The fair reading is narrow: petrelintide produced meaningful weight loss against placebo at 28 to 42 weeks, and incretin drugs produced larger losses over longer periods in larger trials. Whether a longer petrelintide trial narrows or widens that gap is not known.
Tolerability and quitting
This is where the comparison is most tempting and least safe. The three trials do not measure stopping the same way, so the figures below sit side by side only to show how different the definitions are.
Swipe the table sideways to see every column.
| Measure | Semaglutide (STEP 1) | Tirzepatide (SURMOUNT-1) | Petrelintide (ZUPREME-1) |
|---|---|---|---|
| Stopped treatment for stomach or bowel reasons | 4.5% (59 people) vs 0.8% (5) on placebo[6] | Not reported as this category in the abstract | 1.5% vs 0% on placebo[5] |
| Stopped treatment for any adverse event | Not extracted for this page | 4.3% (5 mg), 7.1% (10 mg), 6.2% (15 mg) vs 2.6% on placebo[7] | 4.8% in the maximally effective arm vs 4.9% on placebo (sponsor announcement)[4] |
| Any adverse event | Not extracted for this page | Not extracted for this page | 70.8% vs 69.1% on placebo[5] |
| Nausea | Not extracted for this page | Not extracted for this page | 19.6% vs 6.2% on placebo (pooled arms)[5] |
Evidence categories: STEP 1 and SURMOUNT-1 abstracts (published human trials); ZUPREME-1 discontinuation from the Healio report of the ADA 2026 poster and the Zealand announcement (trade press and sponsor sources, not peer reviewed). “Not extracted” means the figure was not captured for this page, not that it was zero.
One more point on definitions: the three discontinuation rows count different things (stomach or bowel reasons only, versus any adverse event), over different lengths of time (28 to 72 weeks), and with different dose-escalation schedules. The ZUPREME-1 numbers look gentle, but nausea was still about three times the placebo rate in the pooled arms. The petrelintide side-effects guide breaks that down by dose arm. The Phase 1 petrelintide paper also notes that, in a 68-week Phase 3 trial, gastrointestinal events occurred in 54.0% of people on cagrilintide versus 73.8% on semaglutide.[2] That is the paper’s own citation of another trial, which this page did not check at the source.
Is there a head-to-head trial?
No. None of the registered petrelintide trials reviewed for this page lists semaglutide or tirzepatide as a comparator. The Phase 3 trials are designed to measure weight change at week 64 and other outcomes, and the combination trial with Roche’s enicepatide is a Phase 2 dose-finding study.[11] Until a direct comparison exists, every “petrelintide vs semaglutide” ranking is inference built on separate trials.
The closest test so far: CagriSema vs tirzepatide
The only head-to-head result involving an amylin analogue and an approved incretin drug is not about petrelintide. REDEFINE 4 compared CagriSema (cagrilintide, another amylin analogue, plus semaglutide) with tirzepatide 15 mg in 809 adults over 84 weeks, open label. CagriSema produced 20.2% weight loss versus 23.6% for tirzepatide (treatment-regimen estimand), and did not meet the noninferiority criterion.[10] It was reported as a sponsor topline, and no peer-reviewed paper was found. It shows that adding an amylin analogue to an incretin drug did not automatically beat tirzepatide alone. It says nothing direct about petrelintide, a different molecule. See the CagriSema entry and the cagrilintide entry.
What is still unknown
- How much weight petrelintide takes off by week 64, and whether it plateaus.
- How its tolerability compares when measured the same way over the same period.
- Whether combining it with an incretin (Roche is testing enicepatide) beats either drug alone.[11]
- Long-term safety, which the side-effects guide covers in detail.
Frequently asked questions
Is petrelintide better than semaglutide?
Nobody knows. There is no head-to-head trial. In separate trials, semaglutide 2.4 mg produced 14.9% mean weight loss at 68 weeks and petrelintide 7.9% to 9.8% at 28 weeks (up to 10.7% by 42 weeks), but the trials differ in length, analysis method and population.
Is petrelintide stronger than tirzepatide?
There is no evidence that it is. In SURMOUNT-1, tirzepatide produced up to 20.9% mean weight loss at 72 weeks. Petrelintide’s published Phase 2 results are shorter and smaller, and the two drugs have never been compared in the same trial.
Does petrelintide cause less nausea than semaglutide or tirzepatide?
It has not been compared directly. In ZUPREME-1, nausea occurred in 19.6% of petrelintide participants versus 6.2% on placebo, and 1.5% stopped for stomach or bowel reasons versus 0% on placebo. The other trials define and measure these things differently.
Is petrelintide a GLP-1 drug?
No. Petrelintide is an amylin analogue. Semaglutide is a GLP-1 receptor agonist and tirzepatide is a dual GIP and GLP-1 receptor agonist.
Has petrelintide been tested with semaglutide or tirzepatide?
Not in published results. Roche has registered a Phase 2 trial of petrelintide with its own incretin drug enicepatide, which had not started recruiting when the registry was read on 30 October 2026.
Which of the three is approved?
Semaglutide 2.4 mg (Wegovy) was approved by the FDA in June 2021 and tirzepatide (Zepbound) in November 2023 for chronic weight management. Petrelintide is investigational and not approved anywhere.
Why not just compare the percentages?
Because the trials differ in length (28 to 72 weeks), in analysis method, in who was enrolled and in the placebo response. Each of those factors can change a result, so the percentages are not a like-for-like ranking.
Bottom line
Petrelintide is an amylin analogue with a published Phase 2 result of 7.9% to 9.8% weight loss at week 28 versus 1.7% on placebo. Semaglutide and tirzepatide have larger losses over longer periods in larger trials, and are approved. No trial has compared petrelintide with either, and the percentages from separate trials cannot be ranked. The most informative result so far is indirect: adding an amylin analogue to an incretin drug (CagriSema) did not beat tirzepatide in REDEFINE 4. What petrelintide can do over 64 weeks, and in combination, is what the next trials are meant to answer.
Keep reading
Sources
- Garvey WT, Ard J, Connery L, et al. Petrelintide, a human amylin analogue for the treatment of obesity (ZUPREME 1): a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Diabetes Endocrinol. 2026;14(11):914-926. Published 29 September 2026. https://doi.org/10.1016/S2213-8587(26)00213-5 Published human clinical trial (Tier 1). Funded by Zealand Pharma. PMID 42810355. Abstract reviewed.
- Braendholt Olsen M, Griffin J, Hovelmann U, et al. Safety, tolerability, pharmacokinetics, and pharmacodynamics of petrelintide for weight management: two randomized, controlled phase 1 trials. Diabetes Obes Metab. 2026;28(7):5915-5925. Published 22 April 2026. https://doi.org/10.1111/dom.70753 Published human clinical trial (Tier 1). Authors from Zealand Pharma and Profil. PMID 42017294, PMC13243934.
- Garvey WT, et al. ZUPREME-1 poster and slides, American Diabetes Association Scientific Sessions 2026. Zealand Pharma. https://www.zealandpharma.com/media/4lzjvdba/garvey-et-al_zupreme1_ada2026_poster_and_slides.pdf Sponsor conference poster (developer document), not peer reviewed.
- Zealand Pharma. Company announcement No. 3 / 2026: positive phase 2 results for petrelintide (ZUPREME-1 topline). 5 March 2026 (copy distributed by Santelog). https://www.santelog.com/actualites-sante-nasdaq/zealand-pharma-announces-positive-phase-2-results-petrelintide-amylin-analog Company announcement (sponsor-reported, not peer reviewed).
- Healio. Petrelintide, a novel amylin analog, induces 10% weight loss, very well tolerated. 8 June 2026 (Endocrine Today, July 2026 issue). Coverage of ADA Scientific Sessions, New Orleans, 5 to 8 June 2026. https://www.healio.com/news/endocrinology/20260714/petrelintide-a-novel-amylin-analog-induces-10-weight-loss-very-well-tolerated Trade press report of a conference presentation. Not independent confirmation of trial data.
- 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. https://doi.org/10.1056/NEJMoa2032183 Published human clinical trial (Tier 1). Funded by Novo Nordisk. PMID 33567185. Abstract reviewed.
- 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. https://doi.org/10.1056/NEJMoa2206038 Published human clinical trial (Tier 1). Funded by Eli Lilly. PMID 35658024. Abstract reviewed.
- Patient Care Online. FDA approves semaglutide 2.4 mg for chronic weight management in obesity and overweight. 5 June 2021. https://www.patientcareonline.com/view/fda-approves-semaglutide-2-4-mg-for-chronic-weight-management-in-obesity-overweight Trade press report of an FDA approval (approval date 4 June 2021).
- U.S. Food and Drug Administration. FDA approves new medication for chronic weight management. 8 November 2023. https://www.fda.gov/news-events/press-announcements/fda-approves-new-medication-chronic-weight-management Government regulatory announcement (FDA).
- Patient Care Online. CagriSema achieves 23% weight loss but misses noninferiority vs tirzepatide in REDEFINE 4. 23 February 2026. https://www.patientcareonline.com/view/cagrisema-achieves-23-weight-loss-but-misses-noninferiority-vs-tirzepatide-in-redefine-4 Trade-press report of a sponsor topline. No peer-reviewed REDEFINE 4 paper was found.
- ClinicalTrials.gov. NCT07589686: Phase 2 dose-finding study of petrelintide with enicepatide (CT-388). Sponsor: Hoffmann-La Roche. https://clinicaltrials.gov/study/NCT07589686 Trial registry record; not yet recruiting when read on 30 October 2026; no results.
Educational reference only, not medical advice. This page documents what published and registered research reports. It does not tell any reader what to take, and it does not say any compound is safe or effective for any person. Talk to a qualified, licensed clinician about personal medical decisions.
