BI 1820237
BI 1820237, neuropeptide Y receptor type 2 agonist
Written by Aaron CuhaReviewed Sep 2026
Also known as: NPY2R agonist
A first-in-human study in 95 men that found the thing combination therapy has to worry about: its effect on gastric emptying was additive with liraglutide, which is where the nausea comes from.
Overview
Boehringer Ingelheim's entry into the same pathway as the PYY analogue, aimed at the same problem: GLP-1 drugs cause gastrointestinal side effects and some people do not respond to them, so a second satiety receptor is worth targeting.
The phase 1 result is mostly a tolerability story, and a specific one. Drug-related adverse events, mainly gastrointestinal, occurred in 39 percent of participants in the single-agent parts and 30.6 percent in the combination part. More informative than the rates is the mechanism: post-dose paracetamol pharmacokinetics, which is how you measure gastric emptying indirectly, suggested that this drug and low-dose liraglutide had additive effects on slowing the stomach.
That is the honest explanation for why stacking appetite drugs produces stacking nausea, measured rather than assumed.
Mechanism of action
A peptidic agonist at neuropeptide Y receptor type 2, the same receptor PYY(3-36) acts through. Y2 is presynaptic and inhibitory on hypothalamic neuropeptide Y neurons, so agonising it reduces appetite drive. Slowed gastric emptying is part of how that is experienced, and it is also the source of the nausea and vomiting.
Human evidence
One published first-in-human study of single doses in 95 men, reporting safety, tolerability and gastric emptying. No weight loss efficacy result in humans has been published.
- 95 otherwise healthy men with raised BMI, single ascending doses from 0.075 to 2.4 mg, three parts including a liraglutide combination arm.
- Drug-related adverse events, mainly gastrointestinal, in 39.0 percent of the single-agent parts and 30.6 percent of the combination part.
- Transient nausea and vomiting at higher doses.
- Tolerability did not worsen when combined with liraglutide, but gastric emptying effects appeared additive on paracetamol pharmacokinetics.
- This was a single-dose study with tolerability as the primary endpoint. It reports no weight outcome.
What this does not tell you: 95 healthy men given single doses. No women, no repeat dosing, no weight endpoint, and liraglutide 0.6 mg is the starting dose rather than a therapeutic one. The synergy claim comes from mice and has not been demonstrated in people; the trial that could demonstrate it, in combination with survodutide, has not reported. Read this page as a mechanism and tolerability record rather than as evidence the drug works.
Reading the research record
The additive gastric emptying finding is the reason this small phase 1 is worth a page. Combination obesity therapy is usually discussed as if pathways were independent, so benefits would add and side effects would not. Here someone measured, and the slowing of the stomach added up. Nausea and vomiting are the main reason people stop these drugs, so a combination that stacks that effect has a ceiling that has nothing to do with how well it suppresses appetite.
The PYY analogue in this same batch ran into exactly that ceiling in phase 2. Two independent programmes hitting the same receptor family, one showing the mechanism and the other showing the consequence, is a stronger signal than either alone.
The evidence, charted
Fig. 1 · evidence composition
2of 3 citations (67%) are in people
Counted from the citation list on this page. The Human count is the same number shown in the badge at the top. Both understate any literature larger than the sources we cite.
Fig. 2 · evidence over time
Citations here span just two years, 2025 and 2026.
Too few distinct publication years on this page to plot as a timeline.
Fig. 3 · legal status at a glance
US
Not approved
UK
Approved
AU
Approved
CA
Not approved
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.
Key studies & citations
- Human2025
A randomized phase I study of BI 1820237, a novel neuropeptide Y receptor type 2 agonist, alone or in combination with low-dose liraglutide
95 otherwise healthy men with BMI 25.0 to 34.9, three-part partially blinded first-in-human study of single ascending doses from 0.075 to 2.4 mg, with and without liraglutide 0.6 mg. Drug-related adverse events, mainly gastrointestinal, in 39.0% of participants in parts 1 and 2 and 30.6% in part 3. Transient nausea and vomiting at higher doses. No difference in tolerability when combined with liraglutide, and post-dose paracetamol pharmacokinetics suggested additive effects on gastric emptying.
Diabetes, Obesity and Metabolism - Animal2025
Novel NPY2R agonist BI 1820237 provides synergistic anti-obesity efficacy when combined with the GCGR/GLP-1R dual agonist survodutide
The preclinical basis for combining it with survodutide, reporting synergy. Animal work, and the word synergistic belongs to that paper rather than to any human result.
Molecular Metabolism - Human2026
A study of BI 1820237 in combination with survodutide in people with overweight or obesity
The human combination study with survodutide, which is the test of the synergy claim above.
ClinicalTrials.gov
Frequently asked questions
Does BI 1820237 cause weight loss?
Unknown in humans. The published study gave single doses and measured safety, tolerability and gastric emptying, not weight. The synergy claim with survodutide comes from mouse work, and the human combination trial has not reported.
What does the gastric emptying finding mean for me?
It is the measured reason that combining appetite drugs tends to combine the nausea. If you have struggled with gastrointestinal side effects on a GLP-1, this class of add-on is unlikely to be the answer, and the phase 2 result for the related PYY analogue supports that.
How is this different from the PYY analogue?
They hit the same receptor from different starting molecules, and the PYY analogue is further along. Its phase 2 add-on to semaglutide produced an effect its own authors called not clinically meaningful, with a dose ceiling set by tolerability. That is the most likely preview of where this one lands.