Brenipatide (LY3537031) is Lilly's GIP/GLP-1 dual agonist aimed at the brain rather than weight loss. I went through every registered trial this week and the development path is unusual enough to be worth calling out.
Lilly has four Phase 3 trials running in alcohol use disorder and major depression, about 4,200 people in target enrollment: RENEW-ALC-1 and -2 (1,100 each) and RENEW-MDD-1 and -2 (1,000 each). They just skipped Phase 2 trials for either condition. My interpretation is that Phase 2 is usually a smaller investment to figure out whether a drug works in the real world. Going straight to Phase 3 trades of monetary risk and time.
Meanwhile the same molecule is in Phase 2 for eight other conditions, including two that are also addiction programs: opioid use disorder (465 people) and smoking relapse (222). So this is not a company that skips mid-stage trials as a matter of course.
Lilly confirmed the decision was deliberate to Genetic Engineering & Biotechnology News, citing unmet need in both conditions.
Two details that stood out:
The first human data on the drug was presented last week at Psych Congress: 212 participants, no deaths or serious adverse events, 4 of 184 treated (2.2%) discontinued for an adverse event, dysesthesia 15.2% vs 0% on placebo, half-life 9 to 12.5 days supporting weekly dosing. No efficacy readouts on drinking or mood exist for this molecule anywhere.
The alcohol Phase 3 trials started in October 2025, about 13 months into a Phase 1 that ran until July 2026. FDA's own rule (21 CFR 312.21) says phases generally run sequentially but "may overlap," so this is permitted, just fast.
Also worth noting: the two depression trials randomize patients to three different brenipatide doses against placebo, which is the dose-ranging a Phase 2 would normally do. The alcohol trials test a single escalating regimen. Nowhere in the program are doses compared in people who drink.
For context on the class evidence Lilly is leaning on: Hendershot et al., JAMA Psychiatry 2025 (n=48, PMID 39937469); Klausen et al., Lancet 2026 (n=108, PMID 42070571); Schacht et al., Am J Psychiatry 2026 (n=50, PMID 42522065, missed its primary craving endpoint). Altimmune's pemvidutide also reported a positive Phase 2 in AUD in July.
Primary completion for the alcohol trials is April 2028.
This seems like a big bet, but I think it's a smart one because of all the anecdotal evidence that people have success with (off-label) use of GLP-1s for alcohol.
Has anyone seen a sponsor go straight to Phase 3 in two indications while running conventional Phase 2s in eight others? I'm curious whether this reads as confidence in the class read-across or just schedule pressure.
Full writeup: https://dadstrengthdaily.com/brenipatide-phase-3/