With a trillion-dollar market cap and a wildly successful GLP-1 portfolio, Eli Lilly isn’t resting on its laurels. At the Psych Congress 2026, the company presented early-stage data that could support the potential of its next-gen GLP-1 and GIP receptor agonist to treat diseases far beyond obesity.
GLP-1s—and Eli Lilly—have both become synonymous with weight loss, but incretins may have potential beyond treating obesity and type 2 diabetes. Last week, the Indianapolis-based pharma provided evidence for their use in the neuropsychiatric space—specifically, to treat substance disorders and depression.
GLP-1 and GIP receptors are located throughout the body’s organs, including the brain, according to a poster Lilly shared with BioSpace and presented at the Psych Congress 2026 in New Orleans, where the company debuted a long-acting dual GIP/GLP-1 receptor agonist called brenipatide.
While this was the first time Lilly has publicly spoken about brenipatide at a conference, the asset is already in Phase 3 trials for alcohol use disorder (AUD) and major depressive disorder (MDD), according to Rob Nicholson, associate vice president, US & Global Neuroscience Medical Affairs, Psychiatry & Substance Use Disorders.
Lilly presented data at the meeting from a Phase 1 multiple ascending dose study of brenipatide in patients with overweight or obesity and in healthy volunteers. From a tolerability standpoint, Nicholson told BioSpace that overall side effects “in general were mild over the trial.”
“Interestingly, though, and I think noteworthy, is that the likelihood of an individual having a GI [gastrointestinal] side effect was comparable and equal between both those taking brenipatide and placebo,” he said.
Indeed, the overall frequency of GI-related treatment-emergent adverse effects (TEAE) was 25% in both brenipatide- and placebo-treated participants, per Lilly’s poster. Otherwise, TEAEs related to dysesthesia—or unusual touch-based sensations—were reported in 15.2% of brenipatide-treated participants compared to none in those on placebo. Four people discontinued brenipatide treatment due to TEAEs.
Overall, 57.6% of the 184 patients on brenipatide experienced TEAEs, compared to 42.9% of the 28 patients receiving placebo.
The Phase 1 trial, which included 212 individuals with a “wide range” of BMIs and different ethnicities, was intended to measure the safety, pharmacokinetics and pharmacodynamics to determine dosing for the later substance use, psychiatric and immunologic trials, according to Lilly.
Additionally, Nicholson noted, the candidate’s half-life was between nine and 12 days. “We found [that] to be especially interesting for us, given in neurosciences we’re looking at things from a weekly subcutaneous injection perspective,” he said, adding that a half-life of this length means its levels can be sustained between doses, with fewer peaks and troughs. This, along with brenipatide’s dual action mechanism, may have led to lower GI side effects compared to what is typical for GIP/GLP-1 receptor agonists, he said.
Brenipatide is currently being studied in the Phase 3 RENEW-MDD-1 trial for MDD and the Phase 3 RENEW-ALC-1 trial for moderate-to-severe AUD. Topline data for both studies are expected in early 2028. Brenipatide is the first GIP/GLP-1 receptor agonist to be investigated globally across AUD, Lilly said in its presentation.
Lilly, Altimmune, more target addiction
Recent studies have found an association between GLP-1s and a reduced risk of substance abuse and related severe outcomes, and Lilly isn’t the only company exploring their potential in this space.
Altimmune is developing pemvidutide, which targets the GLP-1 and glucagon receptors. Altimmune’s Phase 2 RECLAIM study hit its primary endpoint in July, with a 2.4-mg dose of pemvidutide eliciting a “statistically significant and clinically meaningful reduction in heavy drinking days,” according to a July 28 press release.
Meanwhile, Baseline Therapeutics launched in January with BT-001, a once-weekly GLP-1 analog being tested for AUD, as well as for cocaine and methamphetamine use disorders. The biotech kicked off a Phase 3 trial in AUD in the first quarter, according to its website.
When asked about the potential of GLP-1 and GIP drugs to treat addiction, Nicholson pointed to preclinical evidence showing that incretins could help with dopamine-driven reward-related responses. In someone with a substance use disorder, there “might be some real relevance there,” he said.
Notably, the RENEW-ALC-1 trial’s primary endpoint is not complete abstinence from alcohol but a change in drinking patterns. Less than 3% of people with AUD are treated with any type of medication, Nicholson said. In the U.S., he added, the approved medicines for the condition are intended for people who are looking to achieve abstinence or who want to maintain it.
“If you think through it, there may be a lot of people who live with alcohol use disorder for whom lifelong abstinence may not be what they see as their best outcome or the thing that they’d like to achieve,” Nicholson said, adding that there is recent evidence that shows reducing alcohol use can have meaningful clinical benefits from a health perspective.
As for RENEW-MDD-1, Lilly is primarily evaluating the safety and efficacy of brenipatide compared to placebo in delaying the return of major depressive symptoms.
“More than half the people who have recurrent MDD are going to have more than one episode, and every time you have an episode, it raises your risk for that next episode,” Nicholson said. Currently, he added, no therapies have been approved specifically to delay or reduce the risk of depressive episodes.
While Lilly is taking what Nicholson called the “big bet” moving brenipatide straight to Phase 3 in AUD and MDD, the asset is also being developed in Phase 2 for opioid use disorder, tobacco use disorder, bipolar disorder and schizophrenia. And in immunology, Lilly is running Phase 2 studies of brenipatide in asthma, irritable bowel syndrome and chronic obstructive pulmonary disease (COPD), he noted.
On the neuroscience side, Lilly has made some significant investments in new mechanisms of action; maybe most notably the company’s up to $3.8 billion acquisition of psychedelics developer AtaiBeckley, which closed last week. The company’s lead asset BPL-003, a synthetic form of 5-MeO-DMT, is in mid-stage development for treatment-resistant depression.
“We’re beginning to think through what could be possible there,” Nicholson said of that buy.
“One of the things I appreciate from overall leadership is the continued interest to think, ‘Where do we see unmet needs and what are the places we think we might be able to follow the science?’”
