Brenipatide (LY3537031): GIP/GLP-1 Dual Agonist, Trials and Status

Key facts

• Compound type: synthetic lipidated peptide; a dual incretin receptor agonist.
• Receptors: glucose-dependent insulinotropic polypeptide receptor (GIPR) and glucagon-like peptide-1 receptor (GLP-1R).
• Development code: LY3537031. Brenipatide is its international nonproprietary name (INN) and US adopted name (USAN).
• CAS number: 2408921-49-1. FDA UNII: C3939LZT6J (FDA Global Substance Registration System).
• Reported half-life: 9 to 12 days (phase 1, presented September 2026).
• Highest stage (October 2026): phase 3, in alcohol use disorder and major depressive disorder.
• Approval status (October 2026): not approved in any country.

Most new incretin drugs are tested first in diabetes and obesity. Brenipatide is the exception. Of its nine registered trials, seven are in addiction, mental health or asthma, grouped under the name RENEW. That makes it unusual among dual GIP and GLP-1 agonists: its development is aimed mainly at conditions of the brain and airways rather than metabolism.

How does brenipatide work?

GIP and GLP-1 are the two incretin hormones, released from the gut after a meal. Both act on class B G-protein-coupled receptors and both raise insulin release when blood glucose is high. GLP-1 also slows stomach emptying and acts on appetite centres in the brain. Our guide to GLP-1 peptides covers that class. A single peptide that activates both receptors is a dual incretin agonist; tirzepatide is the established example (Coskun et al., 2018).

Brenipatide's registered chemical name, in the FDA Global Substance Registration System, describes a synthetic peptide with several non-natural amino acids: D-tyrosine at the start of the chain, 2-aminoisobutyric acid, and alpha-methylated leucine and tyrosine. These are standard ways of making a peptide resist the enzymes that would otherwise break it down within minutes. A C20 fatty diacid is attached to a lysine side chain through a linker; fatty acids of this kind bind albumin in the blood, which slows clearance by the kidneys.

The result is a long-lasting molecule. Phase 1 data presented at Psych Congress 2026 reported a half-life of 9 to 12 days (Psychiatric Times, 18 September 2026). For comparison, tirzepatide's half-life is about 5 days according to its prescribing information, and retatrutide's about 6 days (Urva et al., 2022).

Why test an incretin drug in addiction and mental health?

GLP-1 receptors are not only in the gut and pancreas. They are also found in brain areas involved in reward, and in rodents and non-human primates GLP-1 receptor agonists reduce alcohol intake. Prescribers and patients using approved incretin drugs have also reported less interest in alcohol, but reports of that kind are not trial evidence.

The randomised human evidence so far is small and mixed:

• Exenatide, 2022. In 127 treatment-seeking people with alcohol use disorder over 26 weeks, exenatide did not reduce heavy drinking days compared with placebo, the trial's primary outcome. It did reduce brain responses to alcohol cues on imaging, and exploratory analyses found fewer heavy drinking days in a subgroup with obesity (Klausen et al., 2022).
• Semaglutide, 2025. In 48 non-treatment-seeking adults over 9 weeks, low-dose semaglutide reduced the amount of alcohol drunk in a laboratory session, drinks per drinking day and craving, but did not change the number of drinking days. In participants who smoked, cigarettes per day fell more than on placebo (Hendershot et al., 2025).

Both trials were small and both tested GLP-1 receptor agonists alone. What GIP receptor activity adds in the brain is much less studied, so the brenipatide trials are testing two things at once: whether the GLP-1 findings hold at scale, and whether a dual agonist behaves differently.

What trials are running?

As of 30 October 2026, ClinicalTrials.gov lists nine studies of brenipatide or LY3537031. All of the phase 2 and phase 3 trials are randomised, double-blind and placebo-controlled.

• RENEW-ALC-1 (phase 3, NCT07219966): moderate to severe alcohol use disorder, about 1,100 participants, primary outcome change in drinking patterns over up to 56 weeks. Recruiting since October 2025.
• RENEW-MDD-1 (phase 3, NCT07412756): major depressive disorder, about 1,000 participants, added to standard care; primary outcome time to relapse. Recruiting since February 2026.
• RENEW-Smk-1 (phase 2, NCT07223840): adults who have recently quit smoking, about 222 participants; primary outcome continuous abstinence confirmed by carbon monoxide testing over 24 weeks.
• RENEW-Op-1 (phase 2, NCT07420283): opioid use disorder in early recovery, about 465 participants, alongside buprenorphine; primary outcome weeks of abstinence confirmed by urine testing.
• RENEW-Bipolar-1 (phase 2, NCT07286175): bipolar disorder, about 400 participants, added to standard care; primary outcome time to relapse.
• RENEW-Scz-1 (phase 2, NCT07410507): schizophrenia, about 450 participants, added to standard care. Its primary outcome is percentage change in body weight at 52 weeks in participants with a BMI of 25 or more, which points to weight gain on antipsychotic medicines as a target.
• RENEW-Asthma (phase 2, NCT07219173): uncontrolled moderate to severe asthma, about 531 participants; primary outcome the yearly rate of asthma attacks over 52 weeks.
• Phase 1b (NCT07476118): about 150 people with overweight or obesity; primary outcome percentage change in body weight at 29 weeks. Active, not recruiting.
• Phase 1 (NCT04648865): 40 healthy participants given single doses or placebo, run in Japan from December 2020 to June 2021. Completed.

What has been reported so far?

Only phase 1 findings, in a poster at Psych Congress 2026 in New Orleans (15 to 19 September 2026), as reported by Psychiatric Times. Beyond the 9 to 12 day half-life, gastrointestinal effects were the most common adverse events and occurred at comparable rates on brenipatide and placebo; the presenter described tolerability as consistent with the drug class. The poster has not been published as a peer-reviewed paper, and phase 1 studies are too small and short to say anything about efficacy or long-term safety.

How does it compare with tirzepatide, semaglutide and retatrutide?

• Tirzepatide has the same two targets and a shorter half-life, and it is approved for type 2 diabetes and weight management. In SURMOUNT-1, weight fell 15.0% to 20.9% at 72 weeks against 3.1% on placebo (Jastreboff et al., 2022). See Brenipatide vs Tirzepatide.
• Semaglutide acts on the GLP-1 receptor only, and has the most direct trial evidence in alcohol use disorder of any drug in the class. See Brenipatide vs Semaglutide.
• Retatrutide adds the glucagon receptor to GIP and GLP-1. Its phase 3 TRIUMPH-1 trial reported 17.6% to 25.0% weight reduction at 80 weeks against 3.9% on placebo (Jastreboff et al., 2026). See Brenipatide vs Retatrutide.

No trial has compared brenipatide with any of these compounds.

What is not known yet?

• Efficacy. No phase 2 or phase 3 trial has reported. Every claim about effects on drinking, smoking or mood is, for now, a hypothesis.
• The role of GIP. The addiction rationale rests mainly on GLP-1 receptor findings. Whether GIP receptor activity helps, hinders or does nothing in these conditions is untested in humans.
• Weight effects. No weight data have been published. The phase 1b obesity study and the schizophrenia trial will be the first sources.
• Peer-reviewed pharmacology. As of October 2026 there is no peer-reviewed paper on brenipatide in PubMed; the half-life and tolerability figures come from a conference poster.
• Long-term safety. The phase 3 trials run for a year or more and will give the first long-term safety data.

The bottom line

Brenipatide is a long-acting dual GIP and GLP-1 agonist whose development has moved away from metabolism and towards addiction, mood disorders, schizophrenia and asthma. The idea rests on GLP-1 receptors in brain reward areas and on small trials of exenatide and semaglutide with mixed results. Its own evidence is so far limited to phase 1 safety and half-life data. The RENEW trials, the first of which is estimated to complete in 2027, will decide whether that idea holds. As of October 2026 it is not approved anywhere. The brenipatide profile has the full trial register.

References

1. Coskun T, et al. (2018). LY3298176, a novel dual GIP and GLP-1 receptor agonist for the treatment of type 2 diabetes mellitus: From discovery to clinical proof of concept. Molecular Metabolism. PubMed 30473097
2. Goldsmith P, Garhyan P, Yan S, et al. (2026). Brenipatide, a GIP/GLP-1 receptor agonist: clinical data supporting dose selection for substance use, psychiatric, and immunologic disorders. Poster, Psych Congress 2026 Annual Meeting, New Orleans, 15 to 19 September 2026. Reported in Psychiatric Times, 18 September 2026
3. Hendershot CS, et al. (2025). Once-Weekly Semaglutide in Adults With Alcohol Use Disorder: A Randomized Clinical Trial. JAMA Psychiatry. PubMed 39937469
4. Jastreboff AM, et al. (2022). Tirzepatide Once Weekly for the Treatment of Obesity. New England Journal of Medicine. PubMed 35658024
5. Jastreboff AM, et al. (2026). Retatrutide, a Triple Hormone Receptor Agonist, for Treatment of Obesity. New England Journal of Medicine. PubMed 42814954
6. Klausen MK, et al. (2022). Exenatide once weekly for alcohol use disorder investigated in a randomized, placebo-controlled clinical trial. JCI Insight. PubMed 36066977
7. Urva S, et al. (2022). LY3437943, a novel triple GIP, GLP-1, and glucagon receptor agonist in people with type 2 diabetes: a phase 1b, multicentre, double-blind, placebo-controlled, randomised, multiple-ascending dose trial. The Lancet. PubMed 36354040
8. FDA Global Substance Registration System. Brenipatide, UNII C3939LZT6J. FDA UNII record
9. ClinicalTrials.gov. Studies of brenipatide (LY3537031), records read 30 October 2026. ClinicalTrials.gov search