Early Brenipatide Data Shows Substance Use Treatment Potential

Rob Nicholson, PhD, presented phase 1 data on brenipatide, an investigational long-acting dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist dosed weekly by subcutaneous injection.¹ The compound is currently being evaluated across neuroscience and immunology indications. Gastrointestinal effects were the most commonly reported adverse events in the phase 1 trial and occurred at comparable rates in the brenipatide and placebo arms, according to Nicholson, who described the overall tolerability profile as consistent with expectations for the drug class. The drug's half-life ranged from 9-12 days; "That is a prolonged half-life that gives us a durability of exposure that extends beyond the dosing period of a week," Nicholson said. That sustained exposure between weekly doses, combined with the tolerability findings, is what developer Eli Lilly points to as distinguishing brenipatide from approved incretin therapies for patients who may benefit from once-weekly dosing.

Nicholson also outlined the unmet need in alcohol use disorder (AUD) driving the compound's development in that indication. More than 25 million US adults live with AUD, yet fewer than 1 in 10 receive any form of treatment. "When we look at overall from a treatment perspective, less than 3% of those who have alcohol use disorder get any kind of medication at this time," Nicholson said.

The rationale for evaluating brenipatide in AUD includes the distribution of GLP-1 receptors in brain regions beyond the gut, including areas implicated in reward processing, and a hypothesized role for dopaminergic pathways in the compound's effects on reward-related responses.² Nicholson also noted anecdotal reports from patients on approved incretin therapies describing reduced alcohol craving and consumption, along with mood improvements, apart from the drugs' cardiometabolic effects. Those observations, together with the unmet need and underlying receptor biology, informed the decision to pursue an incretin therapy optimized for neuroscience indications. Lilly is also separately studying brenipatide for relapse prevention in tobacco use disorder and, in combination with other medications, for opioid use disorder.

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. Henney AE, Riley DR, Heague M, et al. Relative efficacy of GLP-1 and GLP-1/GIP receptor agonists in the prevention of alcohol-use disorders using a target trial emulation approach. Diabetes Obes Metab. 2026;28(1):137-150.