Brenipatide for Alcohol Use Disorder: Emerging Findings

Eli Lilly's phase 3 program for brenipatide, an investigational long-acting dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist, includes 2 trials enrolling approximately 2,200 patients across 5 continents with alcohol use disorder (AUD).¹ Rather than requiring lifelong abstinence as the sole meaningful outcome, the trials are assessing changes in drinking patterns, an endpoint intended to capture outcomes that may be more attainable and clinically meaningful for many patients with AUD who do not see abstinence as their only viable goal. Efficacy and safety results from the program are expected by mid-2028.

Brenipatide is also being evaluated in recurrent major depressive disorder (MDD). More than half of patients who experience a depressive episode go on to have another, and many remain on maintenance therapy after an acute episode resolves specifically to prevent relapse.² Even with maintenance treatment, an unmet need remains for therapies that can delay or prevent the next episode. "There remains an unmet need to help address those who would like to have something to keep them from having that next episode or delay the time that they get to that next episode," Nicholson said. The cumulative burden that accrues with each recurrence was cited as the clinical rationale for evaluating whether brenipatide can extend time to the next depressive episode.

The broader rationale for brenipatide across psychiatric and substance use indications stems from ongoing work characterizing incretin biology and its potential relevance to the underlying drivers of these conditions, rather than only their symptoms. Beyond the AUD and recurrent MDD program, phase 2 trials are underway evaluating brenipatide in opioid use disorder, tobacco use disorder, bipolar disorder, and schizophrenia.

Dr Nicholson is associate vice president of US & global neuroscience medical affairs in psychiatry and substance use disorders at Eli Lilly.

References

1. Goldsmith P, Garhyan P, Yan S, et al. Brenipatide, a GIP/GLP-1 receptor agonist: clinical data supporting dose selection for substance use, psychiatric, and immunologic disorders. Poster presented at: Psych Congress 2026 Annual Meeting; September 15-19; New Orleans, LA. Accessed September 18, 2026.

2. Hardeveld F, Spijker J, De Graaf R, et al. Recurrence of major depressive disorder across different treatment settings: results from the NESDA study. J Affect Disord. 2013;147(1-3):225-231.