Curious about NNC0165-1875? You’re not alone. This investigational peptide has popped up in obesity-drug conversations as a partner to semaglutide. The twist? It’s not a GLP-1 drug at all. It’s a long-acting analogue of peptide YY (PYY3-36), a natural gut signal that tells your brain you’re getting full. Think of it as satiety’s quiet enforcer—especially at the Y2 receptor—engineered to last longer than the fleeting pulses your gut normally produces.
Here’s everything you need to know—clear, direct, and grounded in what’s publicly available.
What NNC0165-1875 Is (and Isn’t)
NNC0165-1875—sometimes nicknamed “PYY1875”—is a selective Y2 receptor agonist designed as a long-acting analogue of PYY3-36. Translation: it aims to amplify your body’s own fullness cues, for longer, with more predictable effects than the native peptide’s short half-life. It was developed by Novo Nordisk and studied both alone and combined with semaglutide for weight management.
The key idea: leverage satiety via Y2 (PYY pathway) on top of slower gastric emptying and appetite control via GLP-1 (semaglutide). In theory, two complementary levers on appetite and intake.
It’s not FDA-approved, and it’s not available as a prescription product. In Novo Nordisk’s 2023 annual report, the company noted that the phase 1/2 program in combination with semaglutide was completed and that the project was terminated—meaning this candidate is no longer moving forward in their pipeline.
How It’s Supposed to Work (in Plain English)
PYY is a hormone released by your gut after meals. The PYY3-36 fragment binds strongly to Y2 receptors in the brain’s appetite circuits, dialing down hunger and meal size. The native signal fades quickly; a long-acting analogue like NNC0165-1875 tries to stretch that satiety window to help reduce daily calorie intake.
Pairing this with a GLP-1 agonist (like semaglutide) is a rational combo: GLP-1 slows gastric emptying and nudges the brain toward eating less, while PYY-Y2 adds a second, physiologic “you’re full” message. The combo strategy is part of a broader trend in obesity pharmacology—layering mechanisms to get more weight loss at tolerable doses. Evidence with other pairings supports the concept, though every combo has to prove itself.
What The Studies Looked Like
Publicly, we have two main clinical storylines:
- Early-phase work (phase 1): Long-acting PYY analogues—including NNC0165-1875—progressed through first-in-human studies for obesity. These kinds of trials typically assess safety, pharmacokinetics (how long the drug stays around), and early signals on appetite/weight.
- Combination trials with semaglutide:
- NCT03707990: Phase 1 trial evaluating NNC0165-1875 alone or together with semaglutide in people with overweight or obesity.
- NCT04969939: Phase 2 trial testing semaglutide + NNC0165-1875 vs semaglutide alone in people with obesity. Multiple reviews and databases list the study as completed, but results have not been publicly posted in peer-reviewed journals or on the trial registry.
Novo Nordisk’s 2023 annual report then states the combination project was terminated after completing the phase 1/2 work, which is the most definitive status signal we have.
What We Can and Can’t Say About Efficacy
Can we claim that NNC0165-1875 works? Not responsibly. Here’s why:
- Mechanistically, Y2 agonism should reduce appetite and can lower calorie intake in controlled settings. That’s the biological promise of PYY3-36 analogues.
- Practically, for this specific analogue, the phase 2 combo trial completed without public readout, and Novo terminated the project. Without data, we can’t quantify incremental benefit over semaglutide, tolerability trade-offs, or durability.
If you’ve seen claims online that it “beats semaglutide” or “adds X% more weight loss,” those are not supported by published, citable results as of today.
Safety and Tolerability: What’s Typical for This Class
PYY3-36 analogues, like GLP-1 agents, tend to live in the GI side-effect neighborhood—think nausea and fullness—because they operate on the same appetite-regulatory axis that governs gastric comfort. That said, dose, formulation, and titration matter. Without the NNC0165-1875 phase-2 readout, we can’t say whether the combo raised, lowered, or matched the GI burden vs semaglutide alone. That uncertainty likely factored into portfolio decisions. (This is inference about class effects; we lack a public head-to-head outcome for this molecule.)
Why It Still Matters (Even If the Program Ended)
Pipeline “misses” teach the field a lot:
- Mechanism validation: The ongoing interest in PYY-Y2 confirms satiety signaling remains a credible lever in obesity medicine, even if this analogue didn’t advance.
- Combo logic: Developers are still chasing multi-hormone or multi-pathway approaches—GLP-1 with amylin analogues, GLP-1/glucagon co-agonists, and more—because stacking mechanisms can unlock greater efficacy at safer doses.
- Portfolio pruning: Terminations aren’t failures so much as reallocations toward assets with cleaner data, better tolerability, or stronger differentiation.
What’s the Bottom Line for Clinicians and Health Nerds?
- NNC0165-1875 is a long-acting PYY3-36 analogue (Y2 receptor agonist) developed by Novo Nordisk for obesity, studied alone and with semaglutide.
- The phase 2 combination trial completed but has no publicly posted results; Novo’s 2023 annual report says the project was terminated. No approval, no Rx availability.
- The scientific rationale—reinforcing satiety (PYY-Y2) on top of GLP-1 effects—remains sound and continues elsewhere in the field, but the specific molecule isn’t moving forward.
Quick FAQ (Short, Straight, Evidence-Aware)
- Is NNC0165-1875 the same as cagrilintide? No. Cagrilintide is an amylin analogue (AM833); NNC0165-1875 is a PYY analogue targeting Y2. Different hormones, different receptors.
- Will it come to market later under a new name? There’s no public indication of a rebrand or relaunch. If that changes, it would reappear in company reports or new trial registrations. For now, it’s terminated at Novo Nordisk per their 2023 report.
- Why would a promising mechanism be shelved? Many reasons: tolerability, insufficient incremental efficacy, strategic focus, manufacturing, or competitive positioning. Without a readout, we can’t pinpoint which. That’s normal in early-stage drug development.
If You’re Tracking Obesity Science
Watch for three things:
- New PYY analogues (from any sponsor) that solve the tolerability/efficacy puzzle at the Y2 receptor.
- Combo strategies pairing GLP-1 with amylin, glucagon, or GIP—and eventually with non-hormonal mechanisms—to push efficacy while balancing side effects.
- Transparent readouts: robust, peer-reviewed phase-2/3 publications with method details (dose, titration, discontinuation rates), not just headlines.
The Takeaway
NNC0165-1875 was a smart idea—a durable PYY3-36 signal aimed at satiety, tested alongside a market-leading GLP-1. Despite a clean mechanistic narrative, the program did not advance and was terminated after early-phase work. For the field, the message isn’t “PYY doesn’t work”; it’s that this implementation didn’t clear the bar. Keep your eye on next-gen satiety agents and combination regimens—they’re the frontier shaping what “medical weight loss” looks like over the next few years.
Note on evidence: This guide relies on trial registry entries, company reports, and recent reviews. As of today, there are no peer-reviewed, publicly posted phase-2 efficacy data for NNC0165-1875. If and when that changes, the conclusions should be revisited.
