Emerging compound · Phase 3 (dual GIP/GLP-1 agonist, psychiatric indications)

Brenipatide (LY3537031)

A tirzepatide-class drug that Lilly is developing for addiction and depression rather than obesity. It is the clearest sign yet that the incretin mechanism is being taken seriously in psychiatry.

Phase 3

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At a glance

Brenipatide is a once-weekly dual GIP/GLP-1 receptor agonist from Eli Lilly, the same mechanism class as tirzepatide. Lilly is testing it in Phase 3 for alcohol use disorder, in two trials of about 2,200 participants over 56 weeks, and for major depressive disorder in a trial of about 1,000. Coverage of the programme reports that Lilly moved directly from Phase 1 to Phase 3 for both conditions. Phase 2 studies cover tobacco and opioid use disorder, bipolar disorder, and schizophrenia. Phase 1 results presented in September 2026 described pharmacokinetics and tolerability. No efficacy data has been released.

Class: Dual GIP/GLP-1 receptor agonist, once weekly
Sponsor: Eli Lilly
Stage: Phase 3 (alcohol use disorder, depression); Phase 2 in other conditions
Target: Addiction and mood disorders, not weight

What it is

Brenipatide, coded LY3537031, activates the same two receptors as tirzepatide: GIP and GLP-1. What sets it apart is the intended use. Lilly is not developing it for weight loss. Its Phase 3 programme targets alcohol use disorder and depression, with earlier trials in other addictions and in serious mental illness.

The idea grew out of an observation that has followed the GLP-1 drugs since their spread: many people taking them report less interest in alcohol, and sometimes less craving generally. We cover that evidence in GLP-1s and alcohol and mental health and cravings. Brenipatide is the first incretin drug built around that observation from the start.

Current research status

Lilly's Phase 3 programme includes RENEW-ALC-1 and RENEW-ALC-2 in alcohol use disorder, together about 2,200 participants over 56 weeks, and RENEW-MDD-1 in major depressive disorder, about 1,000 participants. Phase 2 studies are running in tobacco use disorder, opioid use disorder, bipolar disorder, and schizophrenia.

Phase 1 results in more than 200 participants were presented at Psych Congress, held September 15 to 19, 2026. Brenipatide is investigational and not approved for any use.

Mechanistic rationale

GLP-1 receptors are found in brain regions involved in reward and motivation, not only in the gut and pancreas. In animal studies, activating them reduces alcohol intake and the rewarding effects of several drugs. Observational data in people taking semaglutide have pointed in the same direction. The hypothesis behind brenipatide is that this effect is real, separable from weight loss, and strong enough to treat addiction.

Whether GIP adds anything to that effect is less clear, and it is one of the questions the programme will answer. The choice of a dual agonist rather than a pure GLP-1 drug suggests Lilly expects the combination to help, but it has not published the reasoning.

Available evidence

Human research

Phase 1 (presented at Psych Congress, September 2026): In more than 200 participants, brenipatide had a half-life of about 9 to 12.5 days, consistent with weekly dosing. Gastrointestinal adverse events occurred in 25% of participants on the drug and 25% on placebo. Dysesthesia, an abnormal or unpleasant skin sensation, occurred in 15.2% on the drug against none on placebo.^[1]

No efficacy data has been released. Phase 1 trials test safety and dosing, not whether a drug works, and the programme's decision to move straight to Phase 3 means those trials will be the first real test of efficacy.

The dysesthesia signal is worth tracking across the class. The FDA noted that altered skin sensation was more frequent at the higher 7.2 mg dose when it approved Wegovy HD in March 2026, and said it was investigating the reaction further.

Why it's interesting

Alcohol use disorder is common, harmful, and undertreated, and the few approved medications are used by a small minority of people who could benefit. A weekly injection with a mechanism people already associate with reduced cravings would be a meaningful addition.

A positive Phase 3 would also change how the incretin class is understood. It would establish an approved psychiatric use for a mechanism so far defined by weight and blood sugar.

Limitations & risks

Everything important is still unknown. There is no efficacy data in any indication, and skipping Phase 2 removes the usual chance to find the right dose and population before committing to large trials. Psychiatric and addiction trials also have high placebo responses, which makes them hard to win.

Two confounders will need to be ruled out. People who feel nauseated drink less, so any effect on alcohol must be shown to go beyond gastrointestinal side effects. People who lose weight may feel better, so any effect on depression must be shown to go beyond weight change. The dysesthesia rate in Phase 1 is also high enough to watch.

Community discussion notes

Brenipatide will be discussed as an "anti-addiction shot", and the framing will run well ahead of the data. Nothing about its efficacy is known yet. It is investigational, and anything sold under that name outside a trial is not the drug.

What it would mean

Brenipatide is a bet that the reduced craving people describe on GLP-1 drugs is a real pharmacological effect, large enough to treat addiction and depression in its own right. Lilly is making that bet at Phase 3 scale with no efficacy data published, which shows conviction and also raises the risk. The trials should give the clearest answer yet on whether incretin drugs act on the brain's reward systems in a clinically useful way.

Frequently asked questions

Is brenipatide a weight-loss drug?

No. It uses the same receptor targets as tirzepatide, but Lilly is developing it for alcohol use disorder, depression, and other psychiatric and addiction conditions, not for obesity.

Why did Lilly skip Phase 2?

Coverage of the programme reports that Lilly moved directly from Phase 1 to Phase 3 for alcohol use disorder and depression. Lilly has not explained the decision in the sources we reviewed. It speeds development but means Phase 3 is the first test of whether the drug works.

Is it the same as tirzepatide?

It acts on the same two receptors, GIP and GLP-1, but it is a different molecule developed for different conditions. It is not a reformulation of tirzepatide.

What is dysesthesia?

An abnormal or unpleasant skin sensation such as tingling, burning, or sensitivity to touch. It occurred in 15.2% of brenipatide participants in Phase 1 against none on placebo.

Is brenipatide available?

No. It is investigational and available only in clinical trials.

References

GEN. Lilly's GIP/GLP-1 candidate brenipatide shows early clinical promise in substance use and psychiatric disorders. September 2026. https://www.genengnews.com/topics/translational-medicine/lillys-gip-glp-1-candidate-brenipatide-shows-early-clinical-promise-in-substance-psych-disorders/
Psychiatric Times. Early brenipatide data shows substance use treatment potential. September 2026. https://www.psychiatrictimes.com/view/early-brenipatide-data-shows-substance-use-treatment-potential
FDA. FDA approves fourth product under National Priority Voucher program: higher-dose semaglutide. March 2026. https://www.fda.gov/news-events/press-announcements/fda-approves-fourth-product-under-national-priority-voucher-program-higher-dose-semaglutide