PYY1875 (NNC0165-1875)_Dosage, benefits & legal status
Also known as NNC0165-1875, PYY 1875, NN9775
A long-acting copy of the gut fullness hormone PYY that Novo Nordisk tested on top of semaglutide. It added 2.15 points of weight loss with frequent nausea, and development ended in 2023.
Common vial size is what vendors typically sell, not a recommendation. Enter your own vial in the calculator.
What is PYY1875 (NNC0165-1875)?
Plain language first. The technical label stays, but it never stands alone.Overview
Semaglutide works by copying GLP-1, a gut hormone that signals fullness, and PYY1875 was Novo Nordisk's attempt to add a second fullness hormone, PYY, for more weight loss. In a phase 2 trial in people already taking semaglutide 2.4 mg, adding 1.0 mg once a week gave 2.15 percentage points more weight loss over 16 weeks (5.55% against 3.06%). Nausea affected 44.7% against 10.7% and vomiting 31.9% against 3.6%, the authors judged the gain not clinically meaningful, and Novo ended development in 2023.
PYY1875 (NNC0165-1875) is a Novo Nordisk analog of PYY3-36, the 34-residue form of peptide YY that intestinal L-cells release after meals and that curbs appetite through Y2 receptors; in a 2003 NEJM crossover study, an infusion of native PYY3-36 cut buffet calorie intake by 30% in obese and 31% in lean volunteers. Novo's discovery work combined amino acid substitutions for Y2 selectivity and stability with a fatty diacid that binds albumin, aiming at once-weekly injection, but the exact structure of PYY1875 has not been published. It was tested as an add-on to semaglutide, since L-cells release PYY alongside GLP-1, and Novo announced in August 2023 that it had ended development after the phase 2.
What it's used for
Nothing. It was tested as a weekly add-on to semaglutide for weight loss until Novo Nordisk ended development in 2023.
How does PYY1875 (NNC0165-1875) work?
What it does in the body, and where.PYY1875 was built to copy PYY, a fullness signal the gut sends after meals, and to last long enough for one injection a week.
- 01The natural signalAfter a meal, L-cells in the intestine release PYY, and the enzyme DPP-4 trims two amino acids off to make PYY3-36, a 34-residue peptide. It acts on Y2 receptors in the brainstem and hypothalamus to reduce hunger, binding Y2 about 100-fold more tightly than Y1 in Novo's reference data (Ki 0.40 against 40 nanomolar). In 2003 an infusion cut buffet calorie intake by 30% in obese and 31% in lean volunteers.
- 02Making it lastNovo screened PYY3-36 variants for amino acid changes that control Y2 selectivity, potency and stability, and attached a fatty diacid so the peptide binds albumin in the blood. The aim was one injection a week; the exact changes in PYY1875 and its half-life in people have not been published.
- 03Stacking on GLP-1L-cells release PYY together with GLP-1, so the plan was to add PYY's signal to semaglutide, as Novo also did with the amylin analog cagrilintide in CagriSema. In the phase 2 the extra loss was 2.15 percentage points over 16 weeks, with nausea in 44.7%. Nausea had also held back an earlier nasal spray of PYY3-36.
What else is it used for?
Each group carries its own evidence level.Approved means regulators have cleared it for that purpose. Investigational means it is in trials. Early research means it is being studied and is not established.
Add-on to semaglutide (phase 2)
tested-and-failed- Human trial83 randomized after a 32-week semaglutide run-in: -5.55% on 1.0 mg against -3.06% on placebo from week 32 to week 48, a difference of -2.15 percentage points (95% CI -4.24 to -0.06; p=0.0437).
- Human trialWeight -4.54 against -2.23 kg, waist -4.80 against -2.69 cm, HbA1c -0.17 against -0.17 points.
- No dataResults were posted on January 8, 2026; Novo had announced the end of development in August 2023.
Tolerability and the dose change
tested-and-failed- Human trialFirst part, 8 per group for 16 weeks plus follow-up (registry results): nausea in 4, 7 and 1 and vomiting in 3, 6 and 0 on 1.0 mg, 2.0 mg and placebo, each with semaglutide; one serious adverse event at 2.0 mg.
- RegulatoryStopping treatment at 2.0 mg was attributed to tolerability issues, and the April 5, 2022, amendment moved the main dose to 1.0 mg.
First-in-human trial (phase 1)
Investigational- human-early88 men aged 18 to 55 with a BMI of 25 to 34.9 received single doses of 0.1 to 2.4 mg alone or 0.03 to 2.4 mg with semaglutide 0.25 mg, about 8 per placebo-controlled group; the 2025 paper's abstract says all doses were tolerated.
- No dataExposure (AUC and peak concentration) was a registered outcome, but no results are posted on the registry.
Native PYY3-36 in people
peer-reviewed-human- Human trialDouble-blind crossover: a PYY3-36 infusion cut buffet calorie intake by 30% in obese and 31% in lean volunteers (both P<0.001).
- Human observationFasting PYY was lower in obese subjects (10.2 against 16.9 pmol/L).
Design and animal work
Early research- Lab studyPYY3-36 variants were screened for amino acid changes that control Y2 selectivity, potency and stability, then given a fatty diacid for albumin binding; PYY1875 was the one taken into trials.
- Animal studyThe analog family lowered blood sugar in db/db mice and, with a GLP-1 drug, in ZSF1 rats; the separate 2025 Obesity paper reports that PYY1875 added weight loss in semaglutide-treated obese male rats.
It is often described as a phase 1/2 drug; the 2025 Obesity paper describes two separate trials, a phase 1 (NCT03707990) and a phase 2 (NCT04969939). Summaries often leave out that Novo Nordisk ended development in August 2023. Novo's 2021 announcement gave around 75 people and 42 weeks; the registry shows 120 enrolled, 83 randomized to the add-on phase and a 48-week treatment span in the second part. Novo said the trial was completed in May 2023, while the registry completion date is January 30, 2023. The 2.15-point result (about 2.2) is often read as total weight loss; it is the extra loss over semaglutide alone in a 16-week add-on window that followed a 32-week semaglutide run-in. The registry summary says participants inject twice weekly: that counts one PYY1875 or placebo shot and one semaglutide shot, and PYY1875 itself was given once weekly. NNC0165-1273 is a different, non-lipidated Novo PYY3-36 analog offered to researchers through Novo's compound-sharing program, not PYY1875.
The published record
Papers and trials about PYY1875 (NNC0165-1875)
4 papers tagged human · 2 not reviews or lab · 1 clinical trial publications
2 registered trials · 1 with posted results
Furthest stage reached: Phase 2, results posted
Counted from Europe PMC indexing, not read by a person; a human tag can land on reviews, commentary or lab papers; clinical trial publications is the narrower count.
At a glance
Four things to know about PYY1875 (NNC0165-1875)
Evidence
Investigational
Category
Weight loss and metabolic
Common vial
Varies
Half-life
Not established
How much, and do you cycle it?
The range, and whether you take breaks.1.0 mg once weekly, added to semaglutide 2.4 mg (phase 2 trial), once weekly (phase 2 trial). Continuous once-weekly dosing in the phase 2; development ended in 2023 Trial dose
The main part of the phase 2 gave weekly semaglutide for a 32-week run-in, then added weekly PYY1875 or placebo for 16 weeks with no breaks. No product exists, so there is no schedule to plan around.
How long does it stay in the body?
The half-life, and where the figure comes from.Not establishedNo figure
No human half-life has been confirmed for this page. The phase 1 registered exposure (AUC and peak concentration) as outcomes, not half-life, and no results are posted on the registry, and the figures in the 2025 Obesity paper have not been verified for this page. It was designed to bind albumin for once-weekly dosing, a design goal rather than a measured value.
Source: ClinicalTrials.gov, NCT03707990 (no results posted)
You can compare this against the whole library to see where it sits.
How do I dose and price it?
Enter your vial and your dose. Pick a mix. We show the draw and the cost.The vial holds a fixed amount of drug. Adding more water does not make more drug, it just spreads it thinner, so you draw a bigger number on the syringe for the same dose.
Choose your mix
Measuring the water1 mL = one full 100-unit syringe.
How do you store it?
Before mixing, and after.Dry powder in the freezer or fridge. Once mixed, fridge, and use within about a month.
Unmixed lyophilized PYY1875 (NNC0165-1875) keeps for a long time cold. Once you add water the clock starts: most reconstituted vials hold up for roughly 28 to 30 days at fridge temperature. Keep it out of light, and do not freeze it after mixing.
What are the side effects and cautions?
Known cautions and warnings for this compound.Who should avoid it
- Not studied in people with diabetes: the phase 2 enrolled adults with a BMI of 30 to 45 and no diabetes
- Not studied as a long-term treatment without semaglutide: everyone in the phase 2 also took semaglutide 2.4 mg, and the phase 1 gave only single doses
- Use outside a trial: development ended in 2023, and no product or published structure exists
Stop and get help
- Repeated vomiting or being unable to keep fluids down: nausea and vomiting were the main problems in the trial
- Abdominal pain that does not settle: it was reported in 4 of 47 on 1.0 mg against none of 28 on semaglutide alone
Common effects
- Nausea in 21 of 47 (44.7%) on 1.0 mg against 3 of 28 (10.7%) on semaglutide alone, from week 32 to week 56, covering the 16-week add-on phase and follow-up
- Vomiting in 15 of 47 (31.9%) against 1 of 28 (3.6%); constipation in 12 of 47 against 4 of 28; diarrhea in 5 of 47 against 0 of 28
- At 2.0 mg in the first 16-week part of the trial, 7 of 8 had nausea and 6 of 8 vomited, against 1 of 8 and 0 of 8 on placebo with semaglutide
- Serious adverse events in 2 of 47 (4.3%) on 1.0 mg against 0 of 28; 3 of 47 withdrew from the add-on phase against none on semaglutide alone
Where this page says nothing is established, that means nobody has studied it, not that a compound is safe.
Is PYY1875 (NNC0165-1875) approved?
And where the numbers on this page come from.No. PYY1875 (NNC0165-1875) was never approved, and its development has ended. There is no legal route to obtain it as a medicine.
- Approval statusInvestigational
- RouteUnder the skin (subcutaneous)
- Checked19 October 2026
- DoseFrom published clinical trials. Not approved by a regulator for this dose.
- Vial sizeFrom what vendors typically list; not a recommendation.
- SourcesClinicalTrials.gov, NCT04969939 posted resultsClinicalTrials.gov, NCT04969939 recordNCT04969939 protocol, version 4.0 (April 5, 2022)ClinicalTrials.gov, NCT03707990Wulff BS et al., Obesity 2025;33:1457-1474Novo Nordisk, first-half 2023 financial statement (Form 6-K, August 10, 2023)Novo Nordisk, first-half 2021 financial statement (Form 6-K, August 4, 2021)Novo Nordisk Annual Report 2019, pipeline tableØstergaard et al., Science Translational Medicine 2025;17(791):eadq6392Østergaard et al., Scientific Reports 2021;11:21179Batterham et al., New England Journal of Medicine 2003;349:941-948UniProt P10082, peptide YY (human)FDA GSRS substance record, peptide YY human (3-36) (UNII 7PQZ90ULIR)Novo Nordisk compound-sharing program, PYY3-36 analog data sheet
What has happened recently
Never approved anywhere; the furthest stage was phase 2, and no orphan, fast track or breakthrough designation was found. Novo Nordisk's 2019 pipeline table described it as a novel analog of the appetite-regulating hormone PYY intended for once-weekly treatment. Its first-in-human trial (NCT03707990) gave single doses to 88 men at one site in Tempe, Arizona, from October 15, 2018, to August 13, 2019, and has no posted results. The phase 2 (NCT04969939) ran in the US from July 15, 2021, to January 30, 2023; Novo had announced it on August 4, 2021, as a 42-week trial in around 75 people, and a protocol amendment on April 5, 2022, lowered the main dose for tolerability. On August 10, 2023, Novo said it had completed the proof-of-concept trial in May 2023 and had "terminated further development of PYY 1875", giving no reason beyond the trial. The preclinical and clinical results were published in Obesity on July 8, 2025, and the phase 2 results were posted on ClinicalTrials.gov on January 8, 2026.
You can compare this against the whole library, or read how to check a seller.
What else is like PYY1875 (NNC0165-1875)?
Others in Fat loss without GLP-1, side by side.If you're weighing PYY1875 (NNC0165-1875), it's worth reading Spexin, 5-Amino-1MQ, and AOD-9604 in the same class.
A long-acting copy of the gut fullness hormone PYY that Novo Nordisk tested on top of semaglutide. It added 2.15 points of weight loss with frequent nausea, and development ended in 2023.
- Dose
- 1.0 mg once weekly, added to semaglutide 2.4 mg (phase 2 trial)
- How often
- Once weekly (phase 2 trial)
An appetite peptide found by computer search, still almost entirely in animals.
- Dose
- Research only
- How often
- Not established
A capsule studied for speeding up metabolism and burning fat.
- Dose
- 2.5 up to 5 mg per day injected (the capsule dose is far higher, see below)
- How often
- Daily, cycled
A growth-hormone fragment marketed for fat loss, with weak proof it works.
- Dose
- 0.3 mg per day
- How often
- Daily
Guides for this compound
- How to Reconstitute a Peptide
Mix peptide powder with bacteriostatic water, step by step.
- How to Read an Insulin Syringe
Read the units, convert to millilitres, and draw the exact dose.
- mcg vs mg: The Peptide Dosing Mistake to Avoid
Your vial says mg and your protocol says mcg. Here is the conversion and how to check it.
- How to Read a Peptide COA
What the purity number does and does not tell you, and how to spot an edited report.
- How to Vet a Peptide Vendor
Independent COAs, HPLC purity, and the red flags that mean walk away.
Sources
- ClinicalTrials.gov, NCT04969939 posted results(2026)120 enrolled; 83 randomized to the add-on phase; weight change -5.55% against -3.06%, a difference of -2.15 percentage points (95% CI -4.24 to -0.06; p=0.0437); side-effect counts by arm.
- ClinicalTrials.gov, NCT04969939 record(2023)Randomized, double-blind phase 2 in the US; adults with a BMI of 30 to 45 and no diabetes; once-weekly PYY1875 1.0 or 2.0 mg with semaglutide 2.4 mg.
- NCT04969939 protocol, version 4.0 (April 5, 2022)(2022)Tolerability problems at 2.0 mg; starting dose lowered, escalation steps added and main maintenance dose changed from 2.0 to 1.0 mg.
- ClinicalTrials.gov, NCT03707990(2019)First-in-human single-dose trial in 88 men at one US site, alone and with semaglutide 0.25 mg; no results posted.
- Wulff BS et al., Obesity 2025;33:1457-1474(2025)Rat, phase 1 and phase 2 results; the add-on effect was modest and not clinically meaningful, and the treatment was not well tolerated.
- Novo Nordisk, first-half 2023 financial statement (Form 6-K, August 10, 2023)(2023)Phase 2 proof-of-concept trial completed in May 2023; Novo terminated further development of PYY 1875.
- Novo Nordisk, first-half 2021 financial statement (Form 6-K, August 4, 2021)(2021)Phase 2 started, expected to enroll around 75 people with obesity for 42 weeks.
- Novo Nordisk Annual Report 2019, pipeline table(2020)A novel analog of the appetite-regulating hormone PYY, intended for once-weekly treatment.
- Østergaard et al., Science Translational Medicine 2025;17(791):eadq6392(2025)Screening of PYY3-36 variants for Y2 selectivity, potency and stability with fatty diacid albumin binding; one analog, PYY1875, progressed to clinical trials.
- Østergaard et al., Scientific Reports 2021;11:21179(2021)Fatty diacid acylation of PYY3-36 extends half-life, with attachment site and linker shaping potency; a lead analog added weight loss to liraglutide in obese minipigs.
- Batterham et al., New England Journal of Medicine 2003;349:941-948(2003)PYY3-36 infusion cut buffet calorie intake by 30% in obese and 31% in lean volunteers (both P<0.001).
- UniProt P10082, peptide YY (human)(2026)36-residue amidated gut hormone; PYY3-36 is a Y2 agonist that reduces appetite; arginine or glycine at position 9.
- FDA GSRS substance record, peptide YY human (3-36) (UNII 7PQZ90ULIR)(2026)34-residue sequence of native PYY3-36 with a C-terminal tyrosine amide.
- Novo Nordisk compound-sharing program, PYY3-36 analog data sheet(2026)Reference binding for PYY3-36: Ki 0.40 nM at Y2 against 40 nM at Y1, 13 nM at Y4 and 3.2 nM at Y5.
Beyond these, 4 records are indexed. Browse the records