The honest answer to “what are petrelintide side effects” is short: mostly nausea, mostly mild, mostly during the first weeks of stepping up. Here are the actual numbers, who reported them, and what nobody knows yet.
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Quick answer: In the published phase 2 trial ZUPREME-1, nausea was the most common adverse event with petrelintide: 79 of 404 participants (20%) versus 5 of 81 on placebo (6%). Vomiting (3% versus 6%), diarrhea (7% versus 7%) and constipation (7% versus 4%) were similar to placebo, and no deaths were reported.[1] The company poster adds that most stomach and bowel events were mild and happened during dose escalation, and that 1.5% stopped treatment because of them.[3] Petrelintide is not approved, and long-term safety is unknown.
Everything on this page describes adverse events reported in trials that Zealand Pharma sponsored (with Roche as Phase 3 partner). It documents what was observed in study participants. It does not predict what any reader would experience, and it is not medical advice. For how the trial doses were structured, see the petrelintide dosage guide. For the drug itself, see the petrelintide research entry.
The headline numbers: ZUPREME-1
ZUPREME-1 is the main peer-reviewed human dataset. It enrolled 485 adults with obesity and no type 2 diabetes who received weekly petrelintide at five dose levels (pooled here as 404 people) or placebo (81 people) for 42 weeks, including dose escalation.[1] These are the adverse events the paper reports by name.
Swipe the table sideways to see every column.
| Adverse event | Petrelintide (n=404) | Placebo (n=81) | Plain-English read |
|---|---|---|---|
| Nausea | 79 people (20%) | 5 people (6%) | About three times the placebo rate. The most common event. |
| Vomiting | 12 people (3%) | 5 people (6%) | Not higher than placebo overall. |
| Diarrhea | 30 people (7%) | 6 people (7%) | The same as placebo. |
| Constipation | 28 people (7%) | 3 people (4%) | Slightly higher, small numbers. |
| Deaths | None reported | None reported | Reported in the abstract. |
Source: published abstract.[1] Evidence category: published human clinical trial (Tier 1), funded by Zealand Pharma. Percentages are rounded as the paper reports them.
The authors summarize it this way: petrelintide had “similar gastrointestinal tolerability to that of placebo apart from predominantly mild nausea during dose escalation.”[1] That is the peer-reviewed wording, and it is more careful than the “placebo-like” language in company announcements.
Side effects by dose arm
The Lancet abstract pools all petrelintide arms. Zealand’s American Diabetes Association 2026 poster breaks the common events out by arm.[3] The poster labels the arms D1 to D5. Their sizes (79, 81, 83, 79 and 82 people) match the Lancet arms in ascending order, so D1 to D5 appear to be the 1.0, 2.5, 5.0, 7.0 and 9.0 mg arms. That mapping is my inference from the matching group sizes, not something the poster states.
Swipe the table sideways to see every column.
| Event | D1 (n=79) | D2 (n=81) | D3 (n=83) | D4 (n=79) | D5 (n=82) | All petrelintide | Placebo |
|---|---|---|---|---|---|---|---|
| Nausea | 19.0% | 12.3% | 22.9% | 15.2% | 28.0% | 19.6% | 6.2% |
| Vomiting | 3.8% | 0% | 0% | 2.5% | 8.5% | 3.0% | 6.2% |
| Diarrhea | 3.8% | 11.1% | 8.4% | 8.9% | 4.9% | 7.4% | 7.4% |
| Constipation | 3.8% | 3.7% | 6.0% | 12.7% | 8.5% | 6.9% | 3.7% |
| Abdominal pain | 2.5% | 2.5% | 2.4% | 5.1% | 7.3% | 4.0% | 3.7% |
| Decreased appetite | 3.8% | 0% | 6.0% | 2.5% | 2.4% | 3.0% | 0% |
| Injection site reactions | 6.3% | 2.5% | 7.2% | 8.9% | 11.0% | 7.2% | 6.2% |
| Fatigue | 2.5% | 8.6% | 8.4% | 8.9% | 9.8% | 7.7% | 4.9% |
| Headache | 3.8% | 0% | 7.2% | 5.1% | 8.5% | 5.0% | 3.7% |
| Hair loss (alopecia) | 0% | 3.7% | 4.8% | 10.1% | 4.9% | 4.7% | 1.2% |
Source: Zealand Pharma ZUPREME-1 poster, ADA 2026.[3] Evidence category: sponsor conference poster, not peer reviewed. The pooled counts match the Lancet abstract (for example nausea 79 of 404).
Three things stand out, and each needs care:
- The top arm had the most nausea. Nausea was 28.0% in the arm that appears to be 9.0 mg, versus 12.3% to 22.9% in the others. With about 80 people per arm the gaps are noisy, but the direction is what you would expect if higher doses cause more nausea.
- Vomiting in that top arm (8.5%) was above the placebo rate (6.2%), even though the pooled rate looks lower than placebo. Pooling hides this. Small counts (7 people) mean it could be chance.
- Hair loss was higher with petrelintide (4.7% versus 1.2%). The poster does not explain why, and the trial was not designed to find out. It is listed here because the gap is noticeable next to the other rows.
How severe, how long, and how many people quit
- Severity: the poster says 77% of stomach and bowel events with petrelintide were mild.[3]
- Timing: those events were reported during dose escalation. The poster gives no week-by-week timing, so how fast they faded is not documented here.[3]
- Stopping because of stomach or bowel events: 1.5% of petrelintide participants (6 of 404) versus 0% on placebo, per the poster and trade coverage of it.[3][4]
- Any adverse event: 70.8% of petrelintide participants versus 69.1% on placebo, as reported by Healio from the ADA presentation.[8]
- Stopping for any adverse event: Zealand’s March 2026 announcement gave 4.8% in the maximally effective arm versus 4.9% on placebo. That is a sponsor-reported figure, not peer reviewed.[9]
- Anti-nausea medicine: trade coverage reports use of anti-nausea medicine in 2.5% to 8.5% of petrelintide participants versus 1.2% of placebo participants.[4]
- Reaching the target dose: 88% to 98% of petrelintide participants reached their assigned dose.[3][4]
- Escalation design: weekly dosing, stepped up every 4 weeks, with escalation lasting 4 to 16 weeks, according to the poster.[3]
The poster also charts overall discontinuations and serious adverse events, but those values are not stated in its text, so they are not repeated here. Check the poster itself if you need them.[3]
What Phase 1 found
The two Phase 1 trials (healthy volunteers and people with overweight) were small, run at one site in Germany, and sponsored by Zealand. They are useful because they tested the whole dose range closely and measured heart rate, injection sites and antibodies.[2]
Swipe the table sideways to see every column.
| Finding | What was reported |
|---|---|
| Serious or severe events | None. No adverse events of special interest (liver, pancreas, gallbladder). |
| Single-dose trial: nausea and vomiting | Only at the two highest single doses (1.4 and 2.4 mg). |
| Weekly dosing, 16 weeks (part 2), nausea | 17% to 33% of petrelintide participants versus 17% on placebo (12 people per arm, so each person is about 8 points). |
| Vomiting in part 2 | Only one participant, who stopped after the third dose because of moderate nausea and vomiting. |
| Decreased appetite | Among the most common events in part 2 (58% to 83% of petrelintide arms versus 42% on placebo). This is the drug’s intended effect. |
| Heart rate | Average pulse about 5 beats per minute below baseline toward the end of treatment. |
| Injection site reactions | All mild and transient. More frequent in the arms that needed up to three injections per dose (5 of 12 in the highest arm versus 2 of 12 on placebo). |
| Antibodies to petrelintide | No participant tested positive. |
| Dose reductions | None needed, though escalation was every 2 weeks. |
Source: Phase 1 paper.[2] Evidence category: published human clinical trial (Tier 1), 132 people dosed, sponsor-authored.
Why nausea happens early
Plain English: petrelintide copies amylin, a hormone that tells the brain you are full and slows how fast the stomach empties. A slower stomach and a stronger “full” signal are exactly what can make a person queasy, especially when the signal is new. That is why the nausea clusters in the escalation weeks, when the dose is changing.[2]
Technical: amylin analogues act on amylin and calcitonin receptors in the brainstem. The Phase 1 authors say the clear dose relationship for nausea and vomiting in the single-dose trial “illustrated the importance of dose escalation” for stomach tolerability.[2] The pulse-rate drop is a known feature of other long-acting amylin drugs, the same paper notes. Decreased appetite is the pharmacology working, not a separate side effect. For more on how amylin drugs differ, see the petrelintide, eloralintide and cagrilintide comparison and the cagrilintide entry.
ZUPREME-2: the type 2 diabetes trial
ZUPREME-2 enrolled 220 adults with overweight or obesity and type 2 diabetes. Zealand’s topline announcement says 1.9% of petrelintide participants stopped for stomach or bowel events versus 1.7% on placebo, that the most common events were stomach and bowel related, “the vast majority” mild and during escalation, and that no unexpected safety signals appeared.[5] Dosing was stepped up every fourth week for up to 16 weeks.[5]
That is a short company statement. It gives no overall adverse event rates, no serious event data and no breakdown by arm. The company says full results will come at a scientific meeting.[5] Treat it as Tier 2 sponsor-reported evidence until the data are public. The registry record for NCT06926842 has no results posted.[7]
Putting the numbers in context
Cross-trial comparisons are unreliable: different people, doses, lengths and definitions. With that warning, ZUPREME-1’s principal investigator, W. Timothy Garvey, told a press conference that petrelintide’s nausea rate was “about half the rate of nausea” seen in GLP-1 trials, according to Healio.[4] That is a speaker’s statement about other trials, not a head-to-head result, and the same article notes the study was sponsor-funded and that he reports an advisory role with Zealand.[4] The Phase 1 authors make a related point from a different angle: in a 68-week phase 3 trial, a different amylin drug, cagrilintide, had stomach-related events in 54.0% of people versus 73.8% for semaglutide.[2] See the CagriSema entry and the GLP-1 and obesity peptide hub for the wider class.
What is not known
- Long-term safety. The longest published petrelintide exposure is 42 weeks.[1] The Phase 3 trials run to week 64 or longer, and the largest does not complete until 2030 (see the dosage guide for the registry details).
- Full ZUPREME-2 safety data. Only a company summary exists so far.[5]
- Muscle and body composition. The abstract does not report them, so claims about “keeping muscle” are untested in this paper.[1]
- Hair loss. Higher with petrelintide in the poster table, unexplained.[3]
- Heart rate and antibodies in the Phase 2 trials. Measured in Phase 1; not in the poster text reviewed here.[2][3]
- Pancreas, liver and gallbladder. Phase 1 found no events of special interest in 132 people. That is too few to rule out rare problems.[2]
- Interactions with other drugs. Not covered in the sources reviewed.
Unregulated supply risks
Petrelintide has no approval anywhere, so nothing sold under its name is the sponsor’s trial product, and none of the safety numbers above apply to it. Unapproved research peptides are not made under the quality controls that apply to an approved drug, so identity, purity, concentration and sterility cannot be assumed from a label. Those are the exact things a third-party certificate of analysis tries to check, and a certificate is only as good as the lab and the batch it covers. That uncertainty sits on top of the trial uncertainty.
Frequently asked questions
What are the side effects of petrelintide?
In ZUPREME-1, nausea was the most common adverse event (20% versus 6% on placebo), mostly mild and during dose escalation. Vomiting (3% versus 6%), diarrhea (7% versus 7%) and constipation (7% versus 4%) were similar to placebo, and no deaths were reported. Reported in a sponsor-funded trial.
Does petrelintide cause nausea?
It did more often than placebo in ZUPREME-1: 79 of 404 petrelintide participants (20%) versus 5 of 81 on placebo (6%). The company poster says stomach and bowel events were mostly mild and happened during dose escalation.
Does petrelintide cause vomiting?
Not more than placebo overall (3% versus 6% in ZUPREME-1). The company poster shows a higher rate in the highest-dose arm (8.5% versus 6.2%), based on 7 people, so small numbers limit the conclusion.
How many people stopped petrelintide because of side effects?
The poster reports 1.5% of petrelintide participants (6 of 404) stopped because of stomach or bowel events in ZUPREME-1. In ZUPREME-2, the company reported 1.9% versus 1.7% on placebo.
Does petrelintide cause hair loss?
Hair loss was reported in 4.7% of petrelintide participants versus 1.2% on placebo in the ZUPREME-1 poster. The poster does not explain it, and the trial was not designed to find a cause.
Are petrelintide side effects milder than other weight-loss drugs?
Not established. A trial investigator said nausea was about half the rate seen in GLP-1 trials, but that is a cross-trial comparison, not a head-to-head study. No trial has compared petrelintide directly with semaglutide or tirzepatide.
Are there long-term safety data for petrelintide?
No. The longest published exposure is 42 weeks. Phase 3 trials run to week 64 or more, with the largest completing in 2030.
Is petrelintide approved?
No. Petrelintide is in Phase 3 development with Zealand Pharma and Roche and is not approved by the FDA, the EMA or any other regulator.
Can you buy petrelintide?
Not as an approved medicine. Some research suppliers list it for laboratory use, including this coming-soon research listing. Those products are not the sponsor’s trial drug and are not covered by any trial data.
Bottom line
The strongest evidence, a peer-reviewed 485-person phase 2 trial, shows petrelintide causing more nausea than placebo (20% versus 6%), mostly mild and during escalation, with vomiting, diarrhea and constipation close to placebo and no deaths.[1] Company data add that 1.5% stopped for stomach or bowel reasons and flag hair loss as higher than placebo.[3] Phase 1 found no serious events in a small group.[2] What is speculative: any claim that petrelintide is gentler than other drugs, which no head-to-head trial has tested. What is missing: long-term data, full diabetes-trial safety data and an approval. Petrelintide is in Phase 3 and approved nowhere.
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. Full text reviewed.
- 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. Only values stated in the text or table were used.
- Healio. Novel amylin drug confers 10% weight loss with adverse events comparable to placebo. 30 September 2026. https://www.healio.com/news/endocrinology/20260930/novel-amylin-drug-confers-10-weight-loss-with-adverse-events-comparable-to-placebo Trade press report including investigator remarks (Tier 5, practitioner-reported). Not independent confirmation of trial data.
- Zealand Pharma. Company announcement No. 54 / 2026: positive phase 2 ZUPREME-2 topline results for petrelintide in people with overweight or obesity and type 2 diabetes. 7 October 2026 (copy distributed by Inderes). https://www.inderes.fi/releases/zealand-pharma-announces-positive-phase-2-zupreme-2-topline-results-for-amylin-analog-petrelintide-in-people-with-overweight-or-obesity-and-type-2-diabetes Company announcement (sponsor-reported, not peer reviewed).
- ClinicalTrials.gov. NCT06662539: Once-weekly petrelintide versus placebo for obesity or overweight with co-morbidities (ZUPREME-1). Sponsor: Zealand Pharma. https://clinicaltrials.gov/study/NCT06662539 Trial registry record.
- ClinicalTrials.gov. NCT06926842: Efficacy and safety of petrelintide in participants with overweight or obesity and type 2 diabetes (ZUPREME-2). Sponsor: Zealand Pharma. https://clinicaltrials.gov/study/NCT06926842 Trial registry record. No results posted.
- Healio. Petrelintide, a novel amylin analog, induces 10% weight loss, very well tolerated. Endocrine Today, July 2026 issue (ADA Scientific Sessions, 5 to 8 June 2026). healio.com Trade press report of a conference presentation. Not independent confirmation of trial data.
- Zealand Pharma. Company announcement No. 3 / 2026: positive phase 2 results for petrelintide (ZUPREME-1 topline). 5 March 2026 (copy distributed by Santelog). santelog.com Company announcement (sponsor-reported, not peer reviewed).
Educational reference only, not medical advice. This page documents adverse events reported in published and registered research. It does not tell any reader what to take, and it does not say any amount is safe or effective. Talk to a qualified, licensed clinician about personal medical decisions.
