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Amycretin Side Effects: What the Trials Actually Measured

Amycretin side effects — what the trials actually measured

Written by Marcus Reinhardt · Lead Analyst, Peptide Insider · LinkedIn

Evidence-first peptide coverage — every claim on this page is linked to its primary source and reviewed against our editorial policy

Citations verified against PubMed · Published: 2026-09-04 · Last updated: 2026-09-07

Amycretin side effects come with a data footprint most research-market peptides never acquire: two Lancet papers, published side by side in 2025, covering 144 people who took it as a daily tablet and 125 who took it as a once-weekly injection, all randomized, double-blind, and placebo-controlled. The tolerability story is the one its two parent mechanisms predict — gastrointestinal events led in both trials, most were mild or moderate, and in the oral trial they climbed with dose. What the abstracts do not give you is a nausea percentage or a placebo-arm event rate, and this page will not manufacture either.

Quick Answer: The Most Common Amycretin Side Effects

By both routes, gastrointestinal events were the most common adverse events. In the 144-person oral trial, 89 participants (62%) reported at least one treatment-emergent adverse event, all mild or moderate; GI events made up 180 (49%) of the 364 events and affected 72 (81%) of those 89 people. In the 125-person subcutaneous phase 1b/2a — up to 36 weeks, 101 on amycretin and 24 on placebo — the most common events were again GI, mostly mild to moderate and resolved by study end. Neither abstract reports a nausea percentage or a placebo event rate. We also searched Reddit for self-reports and found none by name; that search is summarized further down.

★The Documented Experience of 144 Oral and 125 Subcutaneous Trial Participants

The most complete “user experience” of amycretin belongs to the people who took it under observation — 144 in the oral study, 125 in the subcutaneous study, all aged 18–55 with overweight or obesity. In the injected trial, weekly doses escalated from 0.3 mg and weight fell 24.3% by week 36 in the 60 mg group, against a 1.1% loss on placebo.

How tolerable did participants find it? The oral trial reported all adverse events as mild or moderate, with no deaths; the injected trial’s authors called GI events mostly mild to moderate and resolved by study end, while noting that a large number of people left early — most, they report, for reasons unrelated to adverse events.

What that came with: screening, monitoring, pharmaceutical-grade product from Novo Nordisk, and clinician-managed escalation — none of which ships with a research vial.

Compiled from the published trials (PMID 40550231, PMID 40550229) — not from testimonials. When we publish an individual account here, it will be a real person, named with permission.

Research peptide vial

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In This Guide

What Is Amycretin?

Amycretin is Novo Nordisk’s unimolecular GLP-1 and amylin receptor agonist — one peptide activating both receptors that combination therapy reaches with two molecules (PMID 40550231). It has been tested by two routes: a once-daily tablet in a first-in-human phase 1 (PMID 40550229) and a once-weekly injection in a phase 1b/2a running up to 36 weeks. The injected trial’s weight figures are why it is everywhere: 24.3% at 60 mg by week 36, versus a 1.1% loss on placebo. It is not an approved drug anywhere as of this writing; everything sold under this name outside a trial is research-market material.

How It Works — and Why Two Mechanisms Mean Two Sources of Side Effects

GLP-1 agonists and amylin agonists both slow gastric emptying, both act on appetite circuits, and both produce nausea as the cost. Amycretin puts them in one molecule. In cell-based systems it activated GLP-1, amylin, and calcitonin receptors — so it is not a selective amylin agent — and in mice it reached the brain regions that regulate food intake (PMID 40706446). The injected trial’s authors describe the result as a profile “consistent with GLP-1 and amylin agonists,” with “a high frequency of gastrointestinal events” at rates “similar to those seen in early-phase studies of these molecules” (PMID 40550231).

KEY TAKEAWAY

Two appetite mechanisms in one molecule means two sources of GI side effects in one molecule. The injected trial’s own summary is “a high frequency of gastrointestinal events” — flagged as expected for the class, and reported without a percentage. The weight loss that accompanied it was steep: 24.3% at the top dose by week 36.

The Trial Numbers That Matter

Two human datasets carry this page, both from one site in San Antonio. The oral first-in-human phase 1 (PMID 40550229) enrolled 144 participants: 48 in part A (single oral doses of 1, 3, 6, 12, 18, or 25 mg, or placebo), 36 in part B (3, 6, or 12 mg once daily for 10 days, or placebo), and 60 in part C/D (12 weeks of fixed titration to 50 mg once daily, two 50 mg tablets, or two 25 mg tablets, or placebo). The subcutaneous phase 1b/2a (PMID 40550231) randomized 125 participants — 101 to amycretin and 24 to placebo — across five parts: a single-dose part, an escalation part climbing from 0.3 mg to 60 mg weekly over 36 weeks, and three parts escalating to maintenance doses of 20 mg (36 weeks), 5 mg (28 weeks), or 1.25 mg (20 weeks). The scale caveat: 24 placebo participants spread across five parts, 101 active participants across many arms, one site.

Gastrointestinal Side Effects: The Injected Trial’s Real Findings

For once-weekly subcutaneous amycretin, the abstract reports the finding in words, not percentages: the most common treatment-emergent adverse events were gastrointestinal, the majority mild to moderate, and they resolved by the end of the study (PMID 40550231). Then the key sentence: “although a high frequency of gastrointestinal events was reported, rates were similar to those seen in early-phase studies of these molecules.” What is quantified is the other side of the ledger: estimated mean body-weight change was −24.3% versus −1.1% on placebo at 60 mg (week 36), −22.0% versus +1.9% at 20 mg (week 36), −16.2% versus +2.3% at 5 mg (week 28), and −9.7% versus +2.0% at 1.25 mg (week 20), every active arm significant against placebo (p<0.0001 for parts A–D; p=0.0003 for part E).

PERSONAL OBSERVATION — PI EDITORIAL

Reading the two Lancet abstracts side by side, what struck us was the asymmetry in what got quantified. The oral paper counts everything — 364 events, 89 people, 62%, 81% — while the injected paper gives its GI findings in adjectives: “high frequency,” “mild to moderate,” “resolved.” But the trial everyone quotes for its 24.3% is also the trial whose side-effect rate you cannot look up without the full paper. When a listing pairs that figure with “well tolerated,” ask which abstract the second half came from.

Oral Amycretin: What the First-in-Human Tablet Trial Recorded

The oral trial is where the counting happened. Across parts A through D, 364 treatment-emergent adverse events occurred in 89 (62%) of the 144 participants; every one was mild or moderate, and frequency increased in a dose-dependent manner (PMID 40550229). Gastrointestinal events made up 180 (49%) of the 364 events and were observed in 72 (81%) of the 89 participants who reported any event. No deaths were reported, and plasma concentrations were dose-proportional. The 62% pools single-dose, 10-day, and 12-week parts, and active and placebo participants alike — the abstract separates neither amycretin from placebo nor one dose from another. The placebo column we report wherever an abstract gives it is simply absent here, as is any nausea or vomiting rate.

Injection-Site Reactions — and What the Oral Route Changes

Here is what the published abstracts do not report: injection-site reaction rates. The subcutaneous abstract names only gastrointestinal events among the most common adverse events (PMID 40550231), which tells you administration-site events were not a leading category and nothing more precise. The oral trial had no injections to react to (PMID 40550229). A research-market vial is a lyophilized powder to be injected — the trial’s tablet has no grey-market equivalent — so the standard subcutaneous handling picture applies.

PRACTICAL NOTES — STANDARD SUBCUTANEOUS HANDLING

  • Reconstituted solutions brought to room temperature before use are standard practice in clinical settings
  • Site rotation (abdomen, thigh, upper arm) is how trial protocols manage repeated weekly injections
  • Sterile technique — clean site, single-use needles — is non-negotiable in any protocol, trial or lab
  • Our bacteriostatic water guide covers reconstitution handling in detail

Beyond the Gut: Dropouts, Deaths, and the Numbers Not Reported

The oral trial reported no deaths, and every adverse event in it was mild or moderate (PMID 40550229). The subcutaneous abstract does not mention deaths or serious events either way, and we will not read that silence as a count of zero. The finding it does flag: “a large number of participants withdrew from the study, with a high proportion of discontinuations occurring due to reasons unrelated to treatment-emergent adverse events” (PMID 40550231). No dropout count is given. The authors’ framing is that the exits were not the drug’s doing — fair, but a trial with heavy attrition reports its week-36 results on the people who stayed, who are by definition the ones who tolerated it. No cardiovascular, heart-rate, or laboratory findings appear in either abstract.

What Users Report: Self-Reported Effects From Reddit

The two Lancet trials above are the only human record of amycretin, and Reddit adds little. We searched Reddit on September 5, 2026, found 37 relevant posts, and read the comment threads of two, both from 2025, across r/Retatrutide and r/PeptideDiscussion. Everything below is paraphrased and linked, uses no usernames, and describes products nobody verified. Amycretin exists only inside Novo Nordisk’s trials, nobody describes buying it, and no one describes taking it by name.

The larger thread is a press-release discussion. Commenters contrast amycretin with cagrilintide and note the headline weight-loss figure assumed everyone stayed on treatment; one wonders whether it will share the depression and sleepiness some attribute to cagrilintide, which another disputes (r/Retatrutide). Two people there describing personal use mean cagrilintide.

The closest thing to a first-hand account never names the compound. A reply to the availability question describes nine months in an unnamed trial: about 23 kilograms lost, hunger noise gone, bloodwork normalised, constant constipation the poster partly blamed on low water intake, a quiet, “disconnected” feeling on shot day and the day after that a partner noticed, and no improvement in energy (r/PeptideDiscussion). The thread is about amycretin, so that is the likely subject, but the comment could equally describe another incretin trial, and we do not count it as an amycretin report.

The availability question got no answer. Nobody named a source, consistent with trial-only status. A vial sold under this name has no user record behind it; only an identity test can say what it holds.

HOW TO READ SELF-REPORTS

The trials list gastrointestinal events as the leading adverse event; the one unattributed trial account agrees on constipation and adds a two-day flatness after injections that no abstract measures. It is one unverified person who did not name the drug, on pharmaceutical product inside a trial; nothing here speaks to a research vial, and one account cannot establish frequency or causation for anything.

When Side Effects Happen — and When They Fade

No published amycretin data supports a week-by-week side-effect calendar; anyone offering one built it themselves. On resolution: the injected trial’s GI events “resolved by the end of the study” (PMID 40550231) — though “end of study” spans up to 36 weeks and says nothing about how long any individual’s nausea lasted. On onset: every multiple-dose subcutaneous part began at 0.3 mg and escalated, with maintenance held for the final 12 weeks, so the classic GI windows fall in the escalation weeks. The oral trial adds that adverse events “increased in frequency in a dose-dependent manner” (PMID 40550229).

Long-Term Safety: What 36 Weeks Can and Can’t Tell You

The longest published amycretin exposure is 36 weeks — parts B and C of the subcutaneous trial — in a study that randomized 125 people, 24 of them to placebo (PMID 40550231). It is the whole horizon, and thinner than it looks: heavy attrition means the 36-week completers are a subset of a subset, and the abstract doesn’t say how small. The oral record is shorter still — at most 12 weeks of tablets plus a 3-week follow-up (PMID 40550229). No full-year or multi-year amycretin safety data has been published. Anyone describing its long-term profile is forecasting.

Who the Trials Excluded

Trial safety numbers describe trial populations, and amycretin’s are narrow: both trials enrolled adults aged 18–55 — nobody older than 55 has taken amycretin in a published trial. The subcutaneous trial required a BMI of 27.0–39.9 (PMID 40550231); the oral trial’s early parts enrolled BMI 25.0–34.9 and its 12-week part 27.0–39.9 (PMID 40550229). Neither abstract states whether people with type 2 diabetes were included, so we don’t claim either. Every rate on this page was generated in young-to-middle-aged, screened, monitored adults — a boundary no research buyer replicates.

Managing and Minimizing Side Effects: What the Trials Did

The trials’ side-effect management was structural. Every multiple-dose subcutaneous part started at 0.3 mg weekly and climbed toward a maintenance level then held for the last 12 weeks (PMID 40550231). The oral 12-week part used “a fixed titration regimen for all participants,” stepping from 3 or 6 mg up to 50 mg, two 50 mg tablets, or two 25 mg tablets daily (PMID 40550229). No anti-nausea co-medication or dose-reduction rule appears in either abstract. This is trial design, not a protocol recommendation.

Dose and Side Effects: Dose-Dependent, but Not Charted by Arm

The oral trial answers qualitatively: adverse events “increased in frequency in a dose-dependent manner” across single doses of 1 to 25 mg, daily doses of 3 to 12 mg, and titrations reaching two 50 mg tablets a day (PMID 40550229). The injected trial quantifies efficacy, not side effects: weight loss climbed from 9.7% at 1.25 mg to 16.2% at 5 mg, 22.0% at 20 mg, and 24.3% at 60 mg, while GI events were described collectively as high-frequency with no per-arm breakdown (PMID 40550231). The family’s usual pattern — exposure buys effect and side effect together — is our inference here, not a published finding.

DID YOU KNOW

In diet-induced obese rats, 21 days of amycretin reduced total energy intake by 47% and body weight by 18% while maintaining energy expenditure (PMID 40706446). The same paper found it activates calcitonin receptors alongside GLP-1 and amylin receptors.

Amycretin Alone vs Stacked: It Already Is the Stack

Amycretin inverts the usual stacking question. It was built as one molecule to deliver what the research market assembles from two vials — a GLP-1 agonist plus an amylin analogue — so every number on this page is, in a sense, combination data (PMID 40550231). The authors’ line that GI rates were “similar to those seen in early-phase studies of these molecules” is the closest the abstracts come to a verdict on dual agonism’s cost: class-typical, not additive. What has no published human data at all is amycretin stacked with anything further — retatrutide, tirzepatide, a second amylin analogue like petrelintide.

How Amycretin Compares to Cagrilintide, Eloralintide, and Petrelintide

No head-to-head human trial exists among the amylin-class compounds, so every comparison is cross-trial — different populations, durations, cohort sizes, and reporting — and that caveat travels with each claim. Cagrilintide is the non-selective first-generation amylin analogue, with the largest human dataset. Eloralintide is Lilly’s selective amylin receptor agonist, which bet on receptor selectivity to soften the GI profile. Petrelintide is Zealand’s long-acting analogue of human amylin, with two small phase 1 trials behind it. Amycretin is Novo Nordisk’s answer to the co-formulation problem the others are working around: both mechanisms in one peptide (PMID 40550231). The others are positioned as gentler alternatives to high-dose GLP-1s; amycretin is positioned as more powerful, and its abstracts describe the GI cost as class-typical, not reduced. For the GLP-1 side, see our retatrutide side effects breakdown.

Where the Trial Data Stops: The Research-Vial Reality

Everything above describes pharmaceutical-grade amycretin, made by Novo Nordisk and dosed under supervision. A lyophilized vial from a research-chemical storefront shares a molecule name with that product and nothing else verifiable without testing — and half of amycretin’s published safety data comes from a tablet no grey-market seller can replicate. The usual three gaps apply: identity and purity — a batch-matched COA is the only evidence the vial contains dose-accurate amycretin; concentration arithmetic — reconstitution with bacteriostatic water is on the buyer, and our peptide calculator handles the math and deliberately nothing else; and no medical monitoring, the invisible ingredient in every trial safety table. Compounds in this channel are sold strictly for non-human research use.

Sourcing and Verification

Amycretin’s human data landed in 2025, and listings have followed. The checklist doesn’t change: a batch-matched COA naming the compound and quantity, independent third-party testing with a verifiable report number (see our lab-testing guide), and hard skepticism toward any listing quoting the 24.3% figure as though it applied to the vial. Be equally skeptical of any “oral amycretin” listing — peptide powder in a capsule is not the trial tablet. (Disclosure: some links on this site are affiliate links; they don’t change what we report.) Our vendor reviews show what passing documentation looks like, and our guide library covers verification in depth. We don’t yet track live amycretin prices; when our tested vendors stock it, this section gets the live table.

US Regulatory Status

Amycretin is an investigational compound: not FDA-approved anywhere as of this writing — both Lancet papers close by saying the findings “support further investigation” (PMID 40550231, PMID 40550229). Practically, no prescription version exists, every vial in circulation is research-market material sold for non-human research use, and no regulator has evaluated any of those products for identity, purity, or the safety profile above. Our coverage of the FDA’s peptide compounding vote covers the compounding side. When approval status changes, this section changes with it.

PERSONAL OBSERVATION — PI EDITORIAL

In the listings we’ve reviewed for compounds with two headline papers, the pattern is predictable: the best line from each gets stitched together. With amycretin, the 24.3% comes from the injected trial; “all adverse events mild or moderate” comes from the oral trial. Side by side on a product page they describe a compound that sounds better than either paper does alone. Until third-party test results on market product start circulating, the COA is the only sentence of this page that applies to the one in your hand.

Frequently Asked Questions

What are the most common amycretin side effects?

Gastrointestinal events, by both routes. In the oral trial, GI events made up 180 (49%) of 364 adverse events and appeared in 72 (81%) of the 89 participants who reported any. In the injected trial, GI events were the most common category, mostly mild to moderate, resolved by study end. Neither abstract reports a nausea percentage.

What percentage of people had side effects on amycretin?

In the oral trial, 89 of 144 participants (62%) reported at least one treatment-emergent adverse event, all mild or moderate, rising with dose. That figure pools all parts and includes placebo participants; no placebo-only rate is given. The injected trial’s abstract gives no overall percentage.

Is oral amycretin better tolerated than the injection?

The abstracts can’t answer that. The oral trial quantified events over at most 12 weeks; the injected trial ran up to 36 weeks and called GI events high-frequency without a percentage. Different durations, doses, and reporting make the comparison impossible.

How much weight did people lose on amycretin?

In the injected trial: −24.3% at 60 mg (week 36) versus −1.1% on placebo; −22.0% at 20 mg (week 36) versus +1.9%; −16.2% at 5 mg (week 28) versus +2.3%; −9.7% at 1.25 mg (week 20) versus +2.0%. The oral trial’s abstract reports no weight figure.

Is amycretin safe?

Both trials concluded it appeared safe and tolerable — in adults aged 18–55, monitored at a single site, over at most 36 weeks, in a trial many participants left early. Early-phase evidence, and none of it applies to research-market vials.

Why did so many people drop out of the amycretin trial?

The injected trial’s abstract says a large number withdrew, with a high proportion of discontinuations for reasons unrelated to adverse events. It gives no count or breakdown. The practical implication: the week-36 weight figures describe the people who stayed.

Glossary of Terms

  • Unimolecular: one molecule acting on more than one receptor — amycretin hits GLP-1 and amylin receptors from a single peptide.
  • GLP-1 (glucagon-like peptide-1): a gut hormone that slows gastric emptying and reduces appetite.
  • Amylin: a pancreatic hormone that signals fullness; the sole target of cagrilintide, eloralintide, and petrelintide.
  • Calcitonin receptor: closely related to the amylin receptors; amycretin activates it too, making it non-selective.
  • Treatment-emergent adverse event (TEAE): any unwanted medical event after dosing starts, drug-related or not.
  • Multiple ascending dose (MAD): a phase 1 design in which small cohorts receive repeated doses at stepwise higher levels.
  • COA (certificate of analysis): the lab document identifying a research vial’s contents; batch-matched or it proves nothing.

References