What Is Petrelintide? Phase 2 Results, Side Effects and Phase 3 Status

Key facts

Petrelintide is a long-acting human amylin analogue from Zealand Pharma, co-developed with Roche, given once weekly by subcutaneous injection in trials.^[1]^[8]
In the phase 2 ZUPREME-1 trial it cut body weight by up to 10.7% at 42 weeks, against 1.7% on placebo.^[1]
In ZUPREME-2, in people with type 2 diabetes, weight fell by up to 9.2% at 28 weeks (placebo 2.0%).^[6]
Nausea was the most common side effect, in 20% of people on petrelintide against 6% on placebo in ZUPREME-1.^[1]
It is not approved anywhere. Three phase 3 ZUPREME trials with about 7,000 participants started in September and October 2026.^[7]^[9]^[10]

What Is Petrelintide?

Petrelintide is an investigational long-acting amylin analogue from Zealand Pharma, tested at once-weekly maintenance doses of 1.0 to 9.0 mg in its 493-person phase 2 trial.^[1]

Petrelintide at a glance, November 2026.
Feature	Petrelintide
Developer	Zealand Pharma, co-developed and co-commercialised with Roche since March 2025^[8]
Drug class	Long-acting human amylin analogue^[6]
Receptors	Agonist at amylin receptors (AMY1 and AMY3) and the calcitonin receptor^[3]
Dosing in trials	Once weekly, subcutaneous^[1]
Doses studied	0.04 mg to 9.0 mg^[3]^[1]
Half-life	About 10 days^[3]
Best phase 2 result	-10.7% at 42 wk vs -1.7% placebo (ZUPREME-1)^[1]
Most common side effect	Nausea, 20% vs 6% on placebo^[1]
Combination in development	With enicepatide (CT-388), Roche’s GLP-1/GIP receptor dual agonist^[7]
Status	Investigational; phase 3 ZUPREME programme started September 2026^[7]

Roche and Zealand Pharma signed an exclusive collaboration and licensing agreement on 12 March 2025 to develop petrelintide on its own and as a fixed-dose combination with Roche’s incretin CT-388.^[8] Zealand later named CT-388 as enicepatide.^[7] For the hormone petrelintide copies, see what is amylin.

How Petrelintide Works

Petrelintide activates the AMY1 and AMY3 amylin receptors and the calcitonin receptor, and it was designed to stay stable with no fibrillation around neutral pH, so it can be co-formulated with other peptides.^[3]^[2]

It mimics amylin. Amylin is made in pancreatic beta cells and released with insulin after a meal. Zealand says amylin receptor activation reduces body weight by restoring sensitivity to the satiety hormone leptin, so people feel full faster.^[6]
It is built for stability. Petrelintide is highly soluble in water-based formulations and physically stable at neutral pH, which allows co-formulation with other peptide drugs.^[3]
It lasts about 10 days. In phase 1 it was slowly absorbed, had a half-life of about 10 days and showed dose-proportional exposure at steady state, which supports once-weekly dosing.^[3]
It is meant as a combination partner. Roche says its tolerability profile supports its use alongside other drugs, and a phase 2 trial with enicepatide, ZYNERGY, is listed with a planned start of 30 November 2026.^[2]^[12]

Petrelintide Phase 2 Results

In the phase 2 ZUPREME-1 trial, petrelintide cut body weight by 7.9% to 9.8% at 28 weeks and by up to 10.7% at 42 weeks, against 1.7% on placebo.^[1]

ZUPREME-1: mean weight change at 28 weeks (primary endpoint)

Efficacy estimand, adults without type 2 diabetes. Weight kept falling to week 42, reaching up to 10.7%.

Efficacy estimand. Separate trials, not directly comparable.
Trial	Population	Length	Petrelintide	Placebo
ZUPREME-1 (n = 493)	Obesity or overweight, no diabetes	28 wk	-7.9% to -9.8%	-1.7%^[1]
ZUPREME-1 (n = 493)	Obesity or overweight, no diabetes	42 wk	Up to -10.7%	-1.7%^[1]
ZUPREME-2 (n = 220)	Obesity or overweight with type 2 diabetes	28 wk	-7.4% to -9.2%	-2.0%^[6]
Phase 1 MAD part 2	Overweight or obesity	16 wk	Up to -8.6%	Not stated in abstract^[3]

ZUPREME-1 design. 42 weeks, randomised 5:1, double-blind, at 32 sites in Poland, Romania and the USA, registered as NCT06662539. Mean weight was 107.1 kg and mean BMI 36.7; 53% of participants were women.^[1]^[4]
Placebo-adjusted effect. The estimated difference against placebo at week 28 ranged from -6.2% (1.0 and 2.5 mg) to -8.1% (5.0 mg).^[1]
Women and men. Roche reported that women lost considerably more weight than men in ZUPREME-1.^[2]
ZUPREME-2 in type 2 diabetes. Zealand reported on 7 October 2026 an HbA1c fall of up to 0.65% at week 28, against a rise of 0.23% on placebo, a placebo-adjusted fall of 0.61% to 0.88%. Baseline HbA1c was 8.0%.^[6]
Full ZUPREME-2 data have not been published yet; Zealand says they will be presented at a scientific conference. ClinicalTrials.gov lists the trial as completed, with no posted results.^[6]^[5]

Petrelintide Doses in Trials

Petrelintide has been studied at single doses of 0.04 to 2.4 mg and at once-weekly maintenance doses of 1.0, 2.5, 5.0, 7.0 and 9.0 mg in ZUPREME-1.^[3]^[1]

Trial protocols as reported by the publications and the companies. Not dosing advice.
Trial	Doses studied	Escalation as reported	Length
Phase 1 SAD	0.04 to 2.4 mg subcutaneous; 0.35 mg intravenous	Single dose^[3]	Single dose
Phase 1 MAD part 1	0.6 or 1.2 mg once weekly	None^[3]	6 weekly doses
Phase 1 MAD part 2	Target 2.4, 4.8 or 9.0 mg once weekly	Every 2 weeks^[3]	16 weeks
ZUPREME-1, phase 2 (n = 493)	1.0, 2.5, 5.0, 7.0 or 9.0 mg once weekly	Every 4 weeks for up to 16 weeks, then maintenance to week 42^[2]	42 weeks
ZUPREME-2, phase 2 (n = 220)	Three once-weekly doses, not disclosed	Every 4 weeks for up to 16 weeks, then maintenance to week 28^[6]^[5]	28 weeks
ZUPREME-3 and ZUPREME-4, phase 3	Not disclosed	12-week escalation, then maintenance to week 64^[7]	64 weeks

In ZUPREME-1, the 5.0 mg arm gave the largest week-28 weight loss (9.8%); the 7.0 and 9.0 mg arms did not add to it (9.3% and 9.4%).^[1]
Roche says 98% of people in the best-performing ZUPREME-1 cohort reached their maintenance dose.^[2]
Roche also says nausea was less common in ZUPREME-1 than in the earlier 16-week phase 1b, which escalated every second week instead of every fourth.^[2]

This section reports the doses studied in clinical trials. It is not dosing advice, and petrelintide is not approved for any use.

Petrelintide Side Effects

Nausea is the most common side effect of petrelintide, affecting 20% of people (79 of 404) in ZUPREME-1 against 6% on placebo, and it was mostly mild and seen during dose escalation.^[1]

ZUPREME-1, all petrelintide doses (n = 404) vs placebo (n = 81), 42 weeks.
Adverse event	Petrelintide	Placebo
Nausea	20%	6%
Diarrhoea	7%	7%
Constipation	7%	4%
Vomiting	3%	6%

Vomiting was lower than placebo. Across all petrelintide arms, vomiting affected 3% against 6% on placebo, and there was none in the maximally effective arm.^[1]^[2]
Stopping for side effects matched placebo. Discontinuation due to adverse events was 4.8% in the maximally effective arm and 4.9% on placebo. Trial withdrawal for any reason was 8.4% across petrelintide arms against 13.6% on placebo.^[2]
Type 2 diabetes. In ZUPREME-2, 1.9% stopped because of gastrointestinal side effects, against 1.7% on placebo, with no unexpected safety signals.^[6]
Phase 1. Nausea affected 16.7% to 33.3% on petrelintide against 16.7% on placebo in MAD part 2, with no serious or severe adverse events; one person stopped because of gastrointestinal events.^[3]
No deaths were reported in ZUPREME-1.^[1]

Petrelintide Phase 3 and Approval Status

As of November 2026, petrelintide is not approved anywhere; Zealand Pharma announced the start of the phase 3 ZUPREME programme on 22 September 2026, with three trials and about 7,000 participants.^[7]

Phase 3a ZUPREME trials, sponsored by Roche with Zealand Pharma. Primary endpoint: % weight change at week 64.
Trial	Population	Planned size	Start	Primary completion (est.)
ZUPREME-3	Obesity or overweight with a comorbidity, no type 2 diabetes	3,900	30 Sep 2026	Dec 2028^[9]
ZUPREME-4	Obesity or overweight with type 2 diabetes	600	9 Oct 2026	Oct 2028^[10]
ZUPREME-5	Obesity or overweight with established cardiovascular disease	2,500	30 Sep 2026	Jul 2030^[11]

Zealand says the programme is designed to support future marketing applications for petrelintide on its own, and that ZUPREME-5 can last up to three years.^[7] By 7 October 2026 the first participants had started treatment.^[6] Zealand describes the programme as generating the evidence needed to support regulatory filings, so none has been made yet. The only approved amylin analogue is pramlintide; see what is pramlintide.

Petrelintide vs Cagrilintide vs Eloralintide

Petrelintide reached up to 10.7% weight loss at 42 weeks in phase 2, against 10.8% at 26 weeks for cagrilintide 4.5 mg and 20.1% at 48 weeks for eloralintide, but no head-to-head trial exists.^[1]^[13]^[17]

Separate trials with different lengths and populations. Not directly comparable.
Feature	Petrelintide	Cagrilintide	Eloralintide
Developer	Zealand Pharma with Roche^[8]	Novo Nordisk	Eli Lilly
Receptors	AMY1, AMY3 and calcitonin receptor^[3]	Amylin and calcitonin, non-selective^[15]	Selective for AMY1^[16]
Half-life	About 10 days^[3]	159 to 195 hours^[14]	310 to 366 hours^[16]
Best phase 2 result alone	-10.7% at 42 wk^[1]	-10.8% at 26 wk, 4.5 mg^[13]	-20.1% at 48 wk, 9 mg^[17]
Nausea in phase 2	20% vs 6% placebo^[1]	20% to 47% vs 18% placebo^[13]	11% to 64% by arm vs 14% placebo^[18]
Main combination	With enicepatide (CT-388)^[7]	CagriSema (with semaglutide)	EloraTZP (with tirzepatide)
Status (Nov 2026)	Phase 3 (ZUPREME)^[7]	CagriSema filed with FDA Dec 2025^[19]	Phase 3 (ENLIGHTEN)^[20]

Petrelintide’s design focus is tolerability and co-formulation: it is stable at neutral pH, and its phase 2 vomiting rate was below placebo.^[3]^[1] Eloralintide has shown the largest weight loss of the three on its own and is the only one designed to be selective for AMY1.^[17]^[16] Read more: what is cagrilintide, what is eloralintide and eloralintide vs cagrilintide.

Frequently Asked Questions

What is petrelintide?

Petrelintide is an investigational long-acting amylin analogue from Zealand Pharma, co-developed with Roche. It is given once weekly by injection in trials and is being studied for chronic weight management.

How much weight do people lose on petrelintide?

In the phase 2 ZUPREME-1 trial, weight fell by 7.9% to 9.8% at 28 weeks and by up to 10.7% at 42 weeks, against 1.7% on placebo. In ZUPREME-2, in people with type 2 diabetes, it fell by up to 9.2% at 28 weeks against 2.0%.

What are the side effects of petrelintide?

Mostly mild gastrointestinal effects. In ZUPREME-1, nausea affected 20% (placebo 6%), diarrhoea 7% (placebo 7%), constipation 7% (placebo 4%) and vomiting 3% (placebo 6%). Nausea mainly occurred during dose escalation.

Is petrelintide FDA approved?

No. Petrelintide is not approved by the FDA or any other regulator. Its phase 3 ZUPREME programme started in September 2026, and the first phase 3 trial has an estimated primary completion date of December 2028.

What doses of petrelintide were used in trials?

ZUPREME-1 tested once-weekly maintenance doses of 1.0, 2.5, 5.0, 7.0 and 9.0 mg, reached by escalating every 4 weeks. Phase 1 trials used single doses of 0.04 to 2.4 mg and weekly doses up to 9.0 mg. These are trial protocols, not advice.

Is petrelintide better than cagrilintide?

There is no head-to-head trial. Petrelintide reached up to 10.7% weight loss at 42 weeks in phase 2 and cagrilintide 10.8% at 26 weeks, in separate trials with different designs. Petrelintide has a longer half-life of about 10 days, against 159 to 195 hours for cagrilintide.

Sources

For research use only. Not for human or veterinary consumption. This guide summarises published research for information only. It is not medical advice and does not describe any use of products sold on this site.

What Is Petrelintide? Zealand Pharma and Roche’s Once-Weekly Amylin Analogue