NNC0165-1875 dosage and evidence
Written by Aaron CuhaReviewed Sep 2026
The short answer
The clearest test of adding a second appetite hormone to semaglutide, and it failed twice over. The authors call the extra effect modest and not clinically meaningful. People could not tolerate the higher dose.
Evidence grade for NNC0165-1875: Moderate. The rule: at least one finished study in people, and at least 100 people who took it. The sum on this page: 3 completed trials, 120 people given it. A grade counts how much has been done to people, not whether it works.
- People given it
- 120
- Human studies
- 3
- Found nothing
- 0
Dose
No human dose established
Amounts that were given in studies sit in Human evidence on this page. None of them is a personal dose.
3 completed trials, 120 people given it
2 effects reported, 2 unwanted, by people using it, not a trial
Goal pages: Fat loss and metabolism
In plain English
In plain English, from Aaron
This is how I would explain it to a friend. The evidence, with the numbers, is further down the page.
NNC0165-1875 is a long acting copy of PYY, the gut hormone that tells your brain the meal is over. Novo Nordisk tested it as an add-on to semaglutide. The idea was that two fullness signals would add up. It did not work out. It is not approved anywhere.
What people take it for
- More weight loss on top of semaglutide.
- A second appetite signal to stack with a GLP-1 drug.
What studies in people showed
The main trial had 120 people on semaglutide. Adding the 1.0 mg dose gave an extra effect the authors call modest and not clinically meaningful. Stomach and bowel side effects were common. People could not handle the step up to 2.0 mg. So the dose that might have worked could not be given. In rats on semaglutide, it did add weight loss. That did not carry over to people.
What people report
Reports, not study results
The good
- We have not collected user reports on this one yet.
The bad
- Stomach and bowel side effects were common at 1.0 mg.
- People could not tolerate the 2.0 mg dose plan.
Where these come from: The side effects come from the trial on this page. We have no user reports.
My bottom line
My opinion: this is the proof that stacking appetite drugs stacks the nausea too. More is not always more. If one GLP-1 drug is working, protect your muscle with protein and lifting before chasing add-ons.
An opinion, not a finding. I am a coach, not a doctor.
What it has been measured to do
Measured in people
Goals NNC0165-1875 has been tested for in people, biggest studies first. We count only what the studies on this page say, so the real numbers may be higher.
- Losing weightno headcount stated · 1 study
35 of the 36 indexed goals have no study of any kind behind NNC0165-1875
No study in people, animals or cells on this page reports a result for these. That does not prove NNC0165-1875 does nothing for them. It does mean anything you have heard about NNC0165-1875 and one of these did not come from a study cited here.
Show full evidence
What is NNC0165-1875?
The clearest test of adding a second appetite hormone to semaglutide, and it failed twice over. The authors call the extra effect modest and not clinically meaningful. People could not tolerate the higher dose.
Peptide YY, or PYY, is the gut hormone that tells your brain the meal is over. It works through a different switch from GLP-1. On paper that makes it the obvious partner, since two separate fullness signals should add up. Novo Nordisk built a long acting version and tested exactly that. It went from rats, to a first study in people, to a mid-stage trial as an add-on to semaglutide 2.4 mg.
In people, the result was not good. The mid-stage trial had 120 people. The authors wrote that the 1.0 mg dose, added to semaglutide, gave a modest but not clinically meaningful effect compared with a dummy. Stomach and bowel side effects were common at that dose. The plan to step up to 2.0 mg could not be tolerated at all.
In rats already on semaglutide, the added drug did cause extra weight loss. That looked hopeful. It did not carry over to people.
This is the most useful negative result in this group of drugs, because it tests the idea the whole combination approach rests on.
How does NNC0165-1875 work?
It is a long acting copy of PYY(3-36), the short form of peptide YY. Cells in the lower gut release it after you eat. PYY(3-36) works on the Y2 receptor. That switch quiets the brain cells that drive hunger, called neuropeptide Y cells. Because this is a separate path from GLP-1, the hope was that combining them would add up on appetite without adding up on side effects. The trials show that second hope was wrong.
What have studies in people found about NNC0165-1875?
A first study in people and a mid-stage trial are done, and both were published together with the rat work. That is unusually open. The mid-stage add-on result is bad on benefit and bad on side effects.
- Mid-stage trial, 120 people, testing the drug as an add-on to semaglutide 2.4 mg.
- The 1.0 mg dose gave an effect the authors call modest and not clinically meaningful, compared with a dummy on top of semaglutide.
- Stomach and bowel side effects were common at 1.0 mg.
- The plan to step up to 2.0 mg could not be tolerated. So the dose that might have worked could not be given.
- In obese rats already on semaglutide, the drug did cause extra weight loss. The gap between rats and people is worth noting.
What this does not tell you: A 120 person trial cannot rule out a small real effect, and the authors do not say it does. They say the effect was not clinically meaningful. That is a judgement about how big it was, not whether it existed. The more telling part is the side effect ceiling. When the dose that might work cannot be given on top of a GLP-1 drug, the combination fails for a practical reason. Nothing here tests PYY drugs on their own at higher doses.
The state of the research
This trial deserves more attention than it gets. It is the cleanest published test of the idea under the whole combination approach. The idea is that separate appetite paths should add benefit without adding harm. Here the benefit was not clinically meaningful and the harm capped the dose.
That does not doom every combination. Amylin plus GLP-1, in cagrilintide with semaglutide, gave large weight loss in a final-stage trial. So the approach clearly can work. What this result shows is that it does not work automatically. Reading a hopeful rat result as a preview of a human one is exactly the mistake this site exists to flag. Novo Nordisk published the rat data, the first human study and the disappointing mid-stage trial in one paper. That is more than most companies do.
The evidence, in charts
Fig. 1a · how many people
120people, across 1 study in people cited here
| Study | People | Share |
|---|---|---|
| ClinicalTrials.gov 2025 | 120 | 100% |
The whole total is one study of 120. Counts are the number of people each study on this page says it signed up. That includes studies that only watched people and gave nobody the compound. 2 more studies in people give no headcount and are not counted here. Studies still signing people up are left out, and only studies cited on this page are counted.
Fig. 1b · evidence mix
All 3 sources here are studies in people.
- Study in people · done in people3100%
Counted from the list of sources on this page. It counts only what we cite, so there may be more studies out there. A review counts once, however many studies it sums up.
Fig. 2 · evidence over time
Sources here come from just two years, 2021 and 2025.
Too few different years on this page to draw a timeline.
Fig. 3 · legal status at a glance
US
Not approved
UK
Not approved
AU
Not approved
CA
Not approved
Not approved in any of the four countries shown. This is what the law says, not a verdict on the science. See Legal status below for the full text and any notes.
Fig. 4 · how much does what
Nobody has tested different amounts in people
This chart would show how the effect changes as the amount goes up. For this compound, nobody has measured that in people. So we leave it empty. We will not borrow an animal chart and pretend it works the same in people.
Fig. 5 · what the molecule is
- Kind of compound
- Peptide
- Molecule weight
- Modified 34-amino-acid peptide with a half-life-extending modification. No mass asserted; no source loaded states one.
- Half-life
- Stated in words, not a numbersee the exact wording below
- Chain length
- None on file
Half-life as stated on file: Long-acting, engineered for weekly subcutaneous dosing. No specific half-life figure was resolved in the sources loaded.
No amino acid sequence is on file for NNC0165-1875, so none is drawn rather than guessed from a name.
The studies we cite
- Study in people2025Long-acting PYY(3-36) analogue with semaglutide for obesity: from preclinical assessment through randomized clinical studies
Adding this long acting PYY to semaglutide was not worth it, and people could not tolerate the higher dose. In people, the authors describe the effect of the 1.0 mg dose added to semaglutide as modest but not clinically meaningful. Stomach and bowel side effects were common, and the step up to 2.0 mg was not tolerated. The programme also covered a first safety study in people and work in obese rats. In rats already on semaglutide, the added drug did cause extra weight loss.
A programme spanning obese male rats, a phase 1 study and a phase 2 study. In semaglutide-treated obese rats the analogue induced additional weight loss. In phase 1 all doses alone and coadministered with semaglutide were tolerated. In phase 2, verbatim: a modest but not clinically meaningful treatment effect of PYY1875 1.0 mg versus placebo as an add-on to semaglutide 2.4 mg was observed. Gastrointestinal adverse events were common at 1.0 mg and the 2.0 mg dose escalation regimen was not tolerated. The authors conclude the treatment was not well tolerated.
- Study in people2025A trial of NNC0165-1875 and semaglutide in people with overweight or obesity
The registry entry for the trial that did not pay off. Novo Nordisk enrolled 120 people with obesity and completed it in January 2023. The published report describes the added benefit over semaglutide alone as modest and not clinically meaningful, with the higher dose not tolerated. A record like this matters because it fixes what was promised, how many took part, and when it ended, against what was eventually published.
The phase 2 add-on trial record, 120 participants.
- Study in people2021A trial investigating NNC0165-1875 in people with overweight or obesity
The first study in people finished years ago and was never reported on the registry. Novo Nordisk enrolled 88 people who were overweight or obese, testing the peptide alone and alongside semaglutide, and completed it in August 2019. No results have been posted there. What is known about this stage comes from the journal paper above, not from the registry entry.
The earlier phase 1 record.
Where to buy NNC0165-1875
No seller we track lists NNC0165-1875 yet. We read sellers’ public product lists every week, and this section fills in as soon as one does. Every seller, graded
Common questions
Has NNC0165-1875 been tested in people?
Yes. 120 people given it across 3 completed trials cited here, 0 of which found nothing. The clearest test of adding a second appetite hormone to semaglutide, and it failed twice over. The authors call the extra effect modest and not clinically meaningful. People could not tolerate the higher dose.
What is the NNC0165-1875 dosage?
No human dose established. Amounts that were given in studies sit in Human evidence on this page. None of them is a personal dose. 3 completed trials, 120 people given it
Is NNC0165-1875 FDA-approved?
Investigational. Not approved. A mid-stage study finished, and its own authors said the result was too small to matter to patients.
Does adding PYY to semaglutide help?
Not in a useful way, based on the published mid-stage trial. The authors call the extra effect of the 1.0 mg dose modest and not clinically meaningful. People could not tolerate the 2.0 mg plan. So the dose that might have worked could not be given alongside semaglutide.
Why did it work in rats?
In obese rats on semaglutide, the drug did cause extra weight loss. But rats handle stomach side effects differently, and they cannot tell you they feel sick. Nausea is exactly what capped the dose in people. It is a good example of why animal results get their own section on this site.
Does this mean combination drugs do not work?
No. Cagrilintide with semaglutide gave large weight loss in a final-stage trial, so combining paths can clearly work. It means combining does not work automatically, and the side effects stack along with the benefit.