Eli Lilly discloses that GIP/GLP-1 candidate brenipatide is in Phase 3 for depression and alcohol use disorder

Eli Lilly publicly discussed an experimental incretin drug called brenipatide for the first time at the Psych Congress 2026 meeting in New Orleans, and disclosed that the long-acting dual GIP/GLP-1 receptor agonist is already in Phase 3 trials for alcohol use disorder and major depressive disorder ^[1].

The disclosure came from Rob Nicholson, associate vice president of US and global neuroscience medical affairs, psychiatry and substance use disorders at Lilly ^[1]. Brenipatide hits the same two gut hormone receptors as tirzepatide, the molecule in Mounjaro and Zepbound, but it is a separate, unapproved compound being developed mainly for brain and immune conditions rather than weight loss ^[1].

What the early data showed

The poster Lilly presented covered a Phase 1 multiple-ascending-dose study in people with overweight or obesity and in healthy volunteers ^[1]. The trial enrolled 212 people with what Lilly described as a wide range of body mass indexes and different ethnicities, and was designed to measure safety, pharmacokinetics and pharmacodynamics in order to pick doses for later substance use, psychiatric and immunology trials ^[1].

Among the 184 participants who received brenipatide, 57.6% had a treatment-emergent adverse event, compared with 42.9% of the 28 participants on placebo ^[1]. Gastrointestinal side effects — the most familiar downside of GLP-1 drugs — occurred at the same rate in both groups, 25% ^[1]. Side effects involving dysesthesia, or unusual touch sensations, were reported in 15.2% of people on brenipatide and in none on placebo ^[1]. Four people stopped brenipatide because of side effects ^[1].

Nicholson said overall side effects "in general were mild over the trial," and called the matching GI rates between drug and placebo noteworthy ^[1]. He said the drug's half-life ran between nine and 12 days, which he framed as useful for a weekly subcutaneous injection because blood levels stay steadier between doses, with fewer peaks and troughs ^[1]. He suggested that profile, along with the dual mechanism, may explain the lower-than-expected GI effects ^[1]. A Phase 1 tolerability study is not designed to prove a drug works, and no efficacy results in depression or alcohol use disorder have been reported.

The Phase 3 program

Two late-stage trials are underway: RENEW-ALC-1 in moderate-to-severe alcohol use disorder ^[1][2][4] and RENEW-MDD-1 in major depressive disorder ^[1][3]. Topline data for both are expected in early 2028 ^[1].

The alcohol trial's main goal is not complete abstinence but a change in drinking patterns ^[1]. Nicholson said fewer than 3% of people with alcohol use disorder are treated with any medication, and that approved US options are aimed at people seeking or maintaining abstinence ^[1]. In depression, Lilly is primarily testing whether brenipatide beats placebo at delaying the return of major depressive symptoms; Nicholson said no therapies are currently approved specifically to delay or reduce the risk of depressive episodes ^[1].

Lilly is also running Phase 2 studies of brenipatide in opioid use disorder, tobacco use disorder, bipolar disorder and schizophrenia, plus asthma, irritable bowel syndrome and chronic obstructive pulmonary disease ^[1].

Why it matters for patients

Millions of Americans already take GLP-1 drugs for weight and diabetes, and many have wondered whether the reported drop in cravings extends past food. This program is one of the first attempts to answer that with large, randomized trials rather than observational data ^[1]. If the trials succeed, the practical question for patients would be whether a weekly injection could be prescribed for drinking or depression itself — not as a side benefit of weight treatment.

Brenipatide is not approved for any use, and its safety in people with psychiatric conditions has not been established in late-stage testing. The tolerability signals reported so far come from a small early study in people without those conditions ^[1].

Others are pursuing the same idea. Altimmune's pemvidutide, a GLP-1/glucagon drug, hit the primary endpoint of its Phase 2 RECLAIM study in July, with a 2.4-mg dose producing what the company called a statistically significant and clinically meaningful reduction in heavy drinking days ^[1]. Baseline Therapeutics launched in January with BT-001, a once-weekly GLP-1 analog, and started a Phase 3 alcohol trial in the first quarter ^[1].

What happens next

Early 2028 is the expected timing for topline results from both RENEW-ALC-1 and RENEW-MDD-1 ^[1]. Any regulatory filing date has not been disclosed.