Eloralintide and Petrelintide: The Amylin-Only Drugs in Phase 3

Eloralintide and petrelintide are experimental once-weekly injections that copy amylin, a fullness hormone, without any GLP‑1 action. Lilly’s eloralintide produced about 20% weight loss at 48 weeks on its best doses in a published phase 2 trial, against 0.4% on placebo.^[1] Petrelintide, from Zealand Pharma and Roche, produced up to 9.8% at 28 weeks and 10.7% at 42 weeks in its phase 2, with nausea in 20% of people against 6% on placebo and very little vomiting.^[5] Neither is approved. Both are now in phase 3, and the first of those trials are not due to finish until 2028,^[11][12] so no approval is likely before then. The only amylin drug you can get today is pramlintide (Symlin), which is approved for diabetes, not weight loss.^[9]

What “amylin-only” means

Semaglutide and tirzepatide work mainly through the GLP‑1 receptor. Amylin drugs act on a separate set of receptors that respond to amylin, a hormone the pancreas releases with insulin after meals. The drugs on this page act on amylin receptors and nothing else, so any weight they take off comes from that route alone. (Why amylin is interesting, and why it is hard to turn into a medicine, is explained on the cagrilintide page.)

The two leaders take different approaches. Eloralintide is selective: in lab tests it switched on the amylin 1 receptor about 12 times more strongly than the related calcitonin receptor.^[3] Lilly says it is “designed to preferentially activate the amylin 1 receptor.”^[4] In rats, it caused less food aversion than cagrilintide, which acts on these receptors more broadly.^[3] Whether that matters in people is not yet known. Petrelintide takes the other route. It is built on the sequence of human amylin and reworked so it stays stable in a near-neutral solution, which makes it easier to mix with other drugs later on.^[8]

Pramlintide: the amylin drug already approved

Pramlintide (sold as Symlin) has been on the market for years, but only for diabetes. Its label says it is for people with type 1 or type 2 diabetes “who use mealtime insulin therapy” and still have not reached their blood-sugar goal.^[9] Weight loss was never its job, and the label makes the reasons plain:

• It wears off fast. Its half-life is about 48 minutes, so it is injected before each major meal, not once a week.^[9]
• The weight effect was small. In the two type 2 diabetes trials on the label, people on pramlintide lost an average of 1.4 kg and 1.6 kg, while the placebo groups gained 0.3 kg and 0.1 kg.^[9]
• It carries a boxed warning. Used with insulin, it “increases the risk of severe hypoglycemia, particularly in patients with type 1 diabetes,” so the label tells patients to cut their mealtime insulin by half when they start it.^[9]
• Nausea is common. In the long-term type 1 diabetes trials, 48% of people on pramlintide reported nausea, against 17% on placebo.^[9]

Pramlintide showed that amylin could work in people, but it was held back by small effects and dosing at every meal.^[15] The new drugs fix the dosing problem: each is injected once a week. The open question is how much weight they take off without a GLP‑1 drug alongside.

Eloralintide (Eli Lilly)

Eloralintide, also known as LY3841136, first showed weight loss in a 12-week phase 1 trial of 100 people. Doses were given without any gradual increase, and weight fell by 2.6% to 11.3% depending on dose. Stomach side effects were uncommon: 8% reported nausea and 4% vomiting.^[2]

The phase 2 results came out on November 6, 2025, presented at ObesityWeek and published the same day in The Lancet. That makes them peer-reviewed. Its 263 volunteers, recruited at 46 U.S. sites, had a BMI of 30 or more (or 27 or more with a related health problem) and did not have type 2 diabetes. Its main measure was weight change at 48 weeks.^[1]

Sources: the Lancet paper.^[1] The journal rounds to whole numbers; a 2026 review gives the top result as 20.1%.^[16] Two things in this table stand out. First, the weight loss rises steadily with dose, from 9% to about 20%, with no GLP‑1 action at all. Second, the side effects are not just stomach-related. Fatigue was reported by 43% to 46% of people on the 9 mg regimens, against 12% on placebo, and nausea was high in the group that started at 6 mg straight away. Starting low and stepping up (3 mg to 9 mg) cut nausea by more than half compared with starting at 6 mg, at the cost of some weight loss. The groups were small, 24 to 54 people each, so these rates are not precise.

Eloralintide phase 3: the ENLIGHTEN trials

Lilly says it is now running phase 3 trials of eloralintide on its own for obesity, sleep apnea and knee osteoarthritis pain.^[4] Five are registered on ClinicalTrials.gov. All measure weight change at 64 weeks against placebo, and all are recruiting.

Sources: ENLIGHTEN-1,^[10] ENLIGHTEN-2,^[11] ENLIGHTEN-3,^[17] ENLIGHTEN-4^[18] and ENLIGHTEN-6.^[19] ENLIGHTEN-6 is the one to watch if you are already on a GLP‑1 drug and have stalled: it tests whether adding eloralintide helps. Lilly is also pairing eloralintide with tirzepatide; results from a 48-week phase 2b of that combination were presented at the EASD meeting in September 2026, which so far is a conference presentation rather than a paper.^[4]

Petrelintide (Zealand Pharma and Roche)

Petrelintide was discovered by Zealand Pharma, which now develops and plans to sell it with Roche under a 2025 agreement.^[6] In phase 1 it lasted about 10 days in the body and reduced weight by up to 8.6% after 16 weeks.^[7]

The phase 2 trial, ZUPREME‑1, reported in two steps. On March 5, 2026, Roche announced top-line results: up to 10.7% weight loss at 42 weeks against 1.7% on placebo, no vomiting at the most effective dose, and 4.8% of people stopping because of side effects against 4.9% on placebo.^[6] Those were company-reported numbers. The full peer-reviewed paper followed on September 29, 2026, in The Lancet Diabetes & Endocrinology.^[5] It covers 485 adults without type 2 diabetes at 32 sites in Poland, Romania and the U.S. Five in six people were given petrelintide, and its main measure was weight change at 28 weeks.

Weight kept falling after week 28, reaching up to 10.7% by week 42.^[5] The side-effect numbers are the main selling point. Nausea affected 20% of people on petrelintide against 6% on placebo, mostly mild and during the dose increases. Vomiting was 3% against 6%, diarrhea 7% against 7%, and constipation 7% against 4%.^[5]

The weakness is the ceiling. Going from 5 mg to 9 mg added nothing, so higher doses are unlikely to unlock much more on their own. At roughly 10% after 42 weeks, petrelintide on its own is a moderate weight-loss drug. Zealand and Roche present it as a gentler option for long-term use and as a partner for other drugs: in March 2026 Roche said it planned a phase 2 trial combining petrelintide with its own drug CT‑388.^[6]

Petrelintide: what is still to come

• ZUPREME‑2 tests petrelintide in 221 people with type 2 diabetes over 28 weeks. ClinicalTrials.gov lists it as completed in August 2026.^[20] Roche said results were expected in the second half of 2026;^[6] none had been announced by early October 2026.
• ZUPREME‑3, the main phase 3, plans to enroll 3,900 people without diabetes for 64 weeks. It is registered as starting September 30, 2026, is recruiting, and has an estimated primary completion of December 2028.^[12]
• ZUPREME‑4 (600 people with type 2 diabetes, estimated October 2028)^[13] and ZUPREME‑5 (2,500 people with heart disease, estimated July 2030)^[14] started on the same date.

Eloralintide vs petrelintide

The two drugs have never been tested against each other, and their phase 2 trials differ in length, size and population. Read this table as a summary of two separate trials, not a contest.

Sources: eloralintide phase 2^[1] and ENLIGHTEN-2;^[11] petrelintide ZUPREME‑1^[5] and ZUPREME‑4.^[13] On these numbers eloralintide takes off about twice as much weight, but over a longer trial and with more fatigue and, at some doses, more nausea. Petrelintide’s side-effect profile looks closer to placebo. Lilly also has the head start: its phase 3 began about nine months earlier.

The rest of the amylin-only field

A 2026 review counts six long-acting amylin drugs in human trials: cagrilintide, eloralintide, petrelintide, MET‑233i, ABBV‑295 and AZD6234.^[15] Apart from cagrilintide, none of the others has peer-reviewed weight results yet. Here is where they stand on ClinicalTrials.gov.

Sources: SELENE 1,^[21] SELENE 2,^[22] SELENE 3,^[23] APRICUS,^[24] the ABBV‑295 phase 2^[25] and the MET‑233 study.^[26] AstraZeneca went straight from phase 2b into three phase 3 trials, but without published results there is no weight-loss figure to report. Novo Nordisk’s cagrilintide results alone are on the cagrilintide page. Amycretin, recently renamed zenagamtide,^[16] is not on this list because it also acts on the GLP‑1 receptor. The full late-stage field, amylin and otherwise, is on our GLP-1 pipeline tracker.

When could an amylin-only drug be approved?

Not soon. A company files for approval only after its phase 3 trials finish, and FDA’s review comes after that. The earliest estimated finish among these trials is ENLIGHTEN‑2 in January 2028, with the main eloralintide trial due in March 2028.^[10][11] Petrelintide’s first phase 3 results are estimated for October to December 2028,^[12][13] and AstraZeneca’s for August 2028.^[21] No company has given an approval date, and none can be given honestly yet. These are estimates and they often slip.

Combinations may arrive first. Novo Nordisk has already filed CagriSema, which pairs cagrilintide with semaglutide; the status of that filing is on the cagrilintide page and the head-to-head numbers are in CagriSema vs semaglutide in REDEFINE 5.

Can you get eloralintide or petrelintide now?

Only by joining a trial. Both companies call these drugs investigational,^[4][6] and no product containing either one is approved, so no pharmacy can fill a prescription for them. Several of the phase 3 trials above are still recruiting, and ClinicalTrials.gov lists the sites.

Any vial sold online under these names, for example as a “research peptide,” is not the drug Lilly or Zealand tested, and nobody checks what is inside it. FDA has already warned sellers of cagrilintide marketed this way, as the cagrilintide page shows. Our explainers on what cannot legally be compounded and whether peptides are legal set out the rules. If you want weight-loss treatment now, semaglutide and tirzepatide are approved for weight management and have years of safety data behind them.