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MetabolicHuman studies cited: 3

NNC0480-0389

NNC0480-0389, long-acting GIP receptor agonist

Written by Reviewed Sep 2026

Also known as: Long-acting GIP agonist

A GIP receptor agonist being added to semaglutide in phase 2, with 500 participants. Its mirror image, a GIP antagonist added to semaglutide, is in phase 2 at the same time.

Overview

This is the agonist half of the GIP paradox, tested as an add-on rather than as a single molecule. Novo Nordisk makes semaglutide, so pairing it with a separate long-acting GIP receptor agonist is a route to a tirzepatide-like dual mechanism using two drugs instead of one.

The phase 2 dose-finding study enrolled 500 participants and is recorded as completed. No results are published as of this review.

What makes this page worth reading is not the drug on its own. It is that AT673, a GIP receptor antagonist, is in phase 2 being added to the same background drug for the same purpose, and both cannot be the right direction for the same reason.

Mechanism of action

A long-acting agonist at the GIP receptor, a class B1 G protein-coupled receptor that raises cyclic AMP. In the pancreatic beta cell that potentiates glucose-stimulated insulin secretion in a glucose-dependent way. The non-pancreatic actions in adipose tissue and the central nervous system are where the weight effects are thought to originate, and they are less well characterised. Paired with a GLP-1 receptor agonist the intended result resembles tirzepatide's dual activity.

Human evidence

A registered phase 1 and phase 2 programme with no published results. Everything on this page is registry information.

  • Phase 2 dose finding in combination with semaglutide enrolled 500 participants and is recorded as completed.
  • No results are posted on ClinicalTrials.gov and no peer-reviewed publication was located for this compound.
  • An earlier first-in-human programme ran in healthy participants and people with type 2 diabetes.
  • A further combination study is registered.

What this does not tell you: There is no efficacy or safety result to report. A completed 500-person phase 2 with no posted results means the data exists and is not public, which is a statement about what you can know today rather than about the drug. Anything presented as a result for this compound should be traceable to a specific conference presentation or paper.

Reading the research record

This compound sits inside an unresolved contradiction that runs through the whole incretin field. Activating the GIP receptor produces weight loss, which is how tirzepatide works. Blocking the GIP receptor also produces weight loss, which is how maridebart cafraglutide works. Both results come from randomised human trials. As of this review two drugs are in phase 2 adding opposite GIP interventions to the same background drug, semaglutide: NNC0480-0389 agonises the receptor and AT673 antagonises it. Proposed explanations exist, including receptor desensitisation under sustained agonism producing functional antagonism, and differing central versus peripheral effects, but none is established. This site reports the paradox rather than resolving it, because nobody has resolved it.

The evidence, charted

Fig. 1 · evidence composition

3of 3 citations (100%) are in people

Every citation cited here is Human work; no other study type is cited on this page. This count is of our own citation list and understates any literature larger than the sources we cite.

Fig. 2 · evidence over time

Citations here span just two years, 2022 and 2026.

Too few distinct publication years on this page to plot as a timeline.

Fig. 3 · legal status at a glance

Approved in 2 of 4, prescription route in 0, not approved in 2. A jurisdiction's classification is a regulatory fact, not a verdict on the science; see Legal status below for the full text and any notes.

Fig. 4 · dose response

No human dose response curve exists

We draw this figure where the data supports it. For this compound in humans it does not, so the panel stays empty rather than borrowing an animal curve and implying it transfers.

Awaiting a dose ranging studyProducing one takes a trial that gives different amounts to different groups and measures the difference. Nobody has funded that for this compound.

Key studies & citations

  • Human2026

    A research study of NNC0480-0389 and semaglutide in people with type 2 diabetes

    Phase 2 dose finding, 500 participants, in combination with semaglutide. Recorded as completed with no results posted as of this review.

    ClinicalTrials.gov
  • Human2022

    A trial investigating NNC0480-0389 in healthy participants and people with type 2 diabetes

    The earlier first-in-human programme.

    ClinicalTrials.gov
  • Human2026

    A study of NNC0480-0389 in combination with semaglutide

    A further registered study in the combination programme.

    ClinicalTrials.gov

Frequently asked questions

What does this drug do?

It activates the GIP receptor and is being given alongside semaglutide, which activates the GLP-1 receptor. Together that is the same two-receptor combination tirzepatide achieves in one molecule. No results have been published, so what it achieves in people is not yet known publicly.

Why would anyone add GIP to semaglutide instead of just using tirzepatide?

Different manufacturers, for one: the company developing this makes semaglutide and not tirzepatide. Beyond that, separating the two agonists allows each to be dosed independently, which a fixed single molecule does not.

Is there a result yet?

No. A 500-person phase 2 is recorded as completed with no results posted and no publication located. The data exists and is not public.

Related compounds

GIPSemaglutideTirzepatideAT673