The first wave of GLP-1 medicines changed how researchers think about appetite. Brenipatide may help answer a much bigger question: can the same biology alter the pull of alcohol, nicotine and opioids?
Eli Lilly is no longer testing that idea at the edge of its pipeline. The company has advanced brenipatide into two Phase 3 studies for alcohol use disorder, a Phase 2 smoking-relapse study and a Phase 2 opioid-use-disorder study alongside buprenorphine. Separate trials are examining major depressive disorder, bipolar disorder, schizophrenia, asthma, chronic obstructive pulmonary disease and obesity.
That breadth makes brenipatide one of the most unusual incretin programs in development. It also creates an easy trap: a large clinical program can look like proof before results exist.
The accurate story is more interesting. Brenipatide is a serious test of whether long-acting GIP and GLP-1 receptor activation can influence reward, craving and relapse—not merely body weight. The hypothesis has support from animal research, observational data and early randomized work with other GLP-1 medicines. Brenipatide itself, however, still has to demonstrate that it works.
What is brenipatide?
Brenipatide, development code LY3537031, is an investigational peptide from Eli Lilly that activates both the glucose-dependent insulinotropic polypeptide receptor, or GIPR, and the glucagon-like peptide-1 receptor, or GLP-1R.
That receptor combination sounds familiar because tirzepatide also targets GIPR and GLP-1R. The two compounds are not interchangeable. They are different molecules with different pharmacokinetic designs and clinical-development strategies.
Tirzepatide was built and validated around diabetes and obesity. Brenipatide is being developed as a longer-acting research program across metabolic, neuropsychiatric, addiction and inflammatory indications. Public trial records describe subcutaneous administration, but the clinical schedule and dose escalation belong to the controlled trial protocols—not to an improvised human-use protocol.
Brenipatide is also not retatrutide. Retatrutide activates GLP-1, GIP and glucagon receptors and is being developed primarily for obesity and related metabolic disease. Brenipatide is a dual agonist without the glucagon-receptor component.
Why study an incretin drug for addiction?
GLP-1 biology extends beyond glucose control and gastric emptying. GLP-1 receptors are expressed in brain regions involved in motivation, reward learning and the response to reinforcing substances. Preclinical studies have reported that GLP-1 receptor agonism can reduce alcohol intake and alter reward-related behavior in animal models.
Human evidence has begun to move beyond anecdotes. A 2025 randomized clinical trial of once-weekly semaglutide in adults with alcohol use disorder found signals on laboratory alcohol self-administration and several drinking-related outcomes. The study was relatively small and was not a brenipatide trial, but it strengthened the case for testing incretin biology directly in addiction.
The emerging model is not that GLP-1 agonists simply make people nauseated and therefore less interested in alcohol. Researchers are asking whether these signals can change incentive salience—the process through which a cue becomes powerfully “wanted”—and whether that effect can last long enough to reduce harmful consumption or relapse.
GIP makes the question more complex. Its contribution to central reward biology is less clinically established than GLP-1’s, and dual agonism cannot be assumed to produce the same behavioral result as selective GLP-1 activation. That is one reason the brenipatide program matters: it can test the combined mechanism rather than borrowing conclusions from semaglutide.
The two Phase 3 alcohol-use-disorder trials
Lilly has registered two late-stage programs:
RENEW-ALC-1 — NCT07219966: brenipatide versus placebo in adults with moderate-to-severe alcohol use disorder.
RENEW-ALC-2 — NCT07219953: brenipatide versus placebo in adults with alcohol use disorder and hazardous alcohol use.
The public records describe long studies designed to evaluate efficacy and safety over approximately a year. Outcomes include clinically meaningful changes in drinking behavior, alcohol-related measures and craving rather than treating weight loss as the central result.
Moving directly into a substantial Phase 3 program signals that Lilly considers the hypothesis commercially and scientifically important. It does not tell us the answer. As of September 19, 2026, no peer-reviewed Phase 3 efficacy results for brenipatide in alcohol use disorder have been posted.
That distinction is crucial. Trial registration confirms what is being tested, how the study is structured and which outcomes matter. It does not establish that the investigational drug reduces drinking, prevents relapse or improves recovery.
Smoking relapse: a different test of the same idea
The RENEW-Smk-1 Phase 2 study, NCT07223840, is enrolling adults who recently stopped smoking and want to avoid relapse. Lilly lists a target enrollment of 222 participants, a 24-week treatment period and an eight-week safety follow-up.
This trial asks a clean behavioral question: after someone has already quit, can brenipatide lower the probability that nicotine use returns?
That is different from measuring whether a compound makes cigarettes temporarily less appealing. Relapse prevention requires the effect to survive cues, stress and learned routines over time. It is therefore a useful test of whether incretin signaling can influence a durable reward-behavior loop.
Opioid use disorder: brenipatide is being added to established care
Lilly is also running a Phase 2 study in adults with opioid use disorder. The public trial description specifies brenipatide or placebo with buprenorphine.
That design matters. The study is not positioning brenipatide as a replacement for proven medication for opioid use disorder. It is testing whether an incretin-based intervention can add benefit to established care.
The relevant questions may include craving, illicit opioid use, retention in treatment and relapse-related outcomes. Until results are posted, it would be wrong to describe brenipatide as an opioid-addiction treatment or to infer that it can substitute for buprenorphine, methadone or naltrexone.
The broader RENEW program
Brenipatide’s development map extends well beyond substance use:
Phase 3 studies in major depressive disorder;
Phase 2 studies in bipolar disorder and schizophrenia;
Phase 2 studies in asthma and COPD;
an early obesity study evaluating multiple dose levels;
additional metabolic and liver-disease research.
This is not evidence that one peptide treats unrelated diseases. It is evidence that Lilly is testing a biological platform across conditions that share combinations of metabolic dysfunction, inflammation, behavior and central signaling.
The psychiatric studies are especially notable. Weight gain and metabolic disease are common complications in serious mental illness, while reward processing and motivation are central to several psychiatric symptoms. A successful result would still need to show whether benefit came from direct central effects, metabolic improvement, weight change or some combination.
Brenipatide versus tirzepatide, retatrutide and eloralintide
These molecules are often grouped together because they sit in Lilly’s broader metabolic pipeline. Their jobs are not the same.
Brenipatide — LY3537031: dual GIP/GLP-1 receptor agonist; the current program emphasizes addiction, psychiatry, inflammatory disease and exploratory metabolic use.
Tirzepatide: dual GIP/GLP-1 receptor agonist with established approvals in diabetes and obesity; a different molecule with a mature metabolic evidence base.
Retatrutide: GLP-1/GIP/glucagon triple agonist; the development program is centered on obesity and cardiometabolic disease.
Eloralintide — LY3841136: selective amylin-receptor agonist; a different pathway being studied primarily for obesity, including combinations with other agents.
For a closer look at the amylin pathway, see our Eloralintide analysis. For the competitive triple-agonist landscape, read UBT251 vs retatrutide.
The useful comparison is not “which peptide is strongest?” It is which receptor architecture and exposure profile best fit a defined biological problem.
What we know—and what remains unknown
Confirmed
Brenipatide is Lilly’s investigational LY3537031.
It is a dual GIPR/GLP-1R agonist administered subcutaneously in trials.
Lilly has registered Phase 3 alcohol-use-disorder studies.
Phase 2 programs include smoking relapse and opioid use disorder.
The opioid study adds brenipatide to buprenorphine rather than replacing it.
Brenipatide is not approved for addiction, obesity or any other indication.
Not yet established
Whether brenipatide reduces heavy-drinking days or produces sustained abstinence.
Whether it prevents smoking relapse.
Whether it improves outcomes when added to buprenorphine.
How much of any behavioral effect is independent of weight loss, reduced appetite or gastrointestinal adverse effects.
Whether dual GIP/GLP-1 activation is better for addiction than selective GLP-1 activation.
The long-term psychiatric and metabolic safety profile in these populations.
This is the right place for scientific restraint—not because the program is uninteresting, but because its importance depends on results that the trials are designed to produce.
Why the clinical program matters now
For years, reduced alcohol interest on GLP-1 medicines was discussed mainly through patient anecdotes and retrospective datasets. Those signals were valuable enough to generate hypotheses, but they could not separate drug effect from weight loss, illness behavior, reduced food intake, expectations or other confounders.
Brenipatide changes the quality of the question. Dedicated randomized studies can prospectively measure drinking, craving, relapse and treatment retention. They can also track whether benefit persists after accounting for body-weight change and tolerability.
If the trials succeed, incretin pharmacology could become a new tool in addiction medicine. If they fail, the result will still be informative: it would show that encouraging signals from other GLP-1 drugs or observational studies do not automatically generalize to a purpose-built dual agonist.
Either outcome advances the field.
What researchers should watch
Five details will determine whether the headlines are justified:
The primary endpoint. A change in craving score is not equivalent to fewer heavy-drinking days, sustained abstinence or reduced relapse.
Retention and missing data. Addiction trials can lose participants for reasons related to the outcome itself.
Weight-loss mediation. Analyses should separate direct behavioral effects from the consequences of appetite suppression and body-weight change.
Tolerability. Nausea or reduced intake can temporarily suppress consumption without creating durable recovery.
Effect after treatment. The most important question may be what happens when exposure stops.
The PFC neuroscience research overview explains why receptor location, exposure and behavioral endpoints matter when interpreting peptide research involving the brain.
The bottom line
Brenipatide is one of the clearest signs that the incretin field is moving beyond weight loss. Lilly is testing a dual GIP/GLP-1 agonist in Phase 3 alcohol-use-disorder studies and in Phase 2 programs for smoking relapse and opioid use disorder.
That is a substantial clinical commitment, not a social-media rumor. It is also not an efficacy result.
The most compelling story is the question Brenipatide allows researchers to ask: can a long-acting metabolic signal change the learned reward loops that sustain addiction? The answer now belongs to randomized trials rather than anecdotes.
Frequently asked questions
What is brenipatide?
Brenipatide, or LY3537031, is an investigational Eli Lilly peptide that activates GIP and GLP-1 receptors. It is being studied across addiction, psychiatric, inflammatory and metabolic conditions.
Is brenipatide the same as tirzepatide?
No. Both activate GIP and GLP-1 receptors, but they are different molecules with different exposure profiles and development programs. Tirzepatide has approved metabolic indications; brenipatide remains investigational.
Is brenipatide being studied for alcohol addiction?
Yes. Lilly has registered two Phase 3 studies in alcohol use disorder: RENEW-ALC-1 and RENEW-ALC-2. Results establishing efficacy have not yet been posted.
Is brenipatide being studied for smoking cessation?
It is being studied for prevention of smoking relapse in adults who recently quit. The Phase 2 RENEW-Smk-1 study plans a 24-week treatment period.
Is brenipatide being tested for opioid use disorder?
Yes. A Phase 2 study is testing brenipatide versus placebo in participants receiving buprenorphine. The design evaluates brenipatide as an add-on, not a replacement for established medication.
Is brenipatide approved by the FDA?
No. Brenipatide is an investigational compound and is not approved for addiction, obesity or another indication.
Does brenipatide cause weight loss?
Weight and metabolic effects are being evaluated, including in an early obesity study. Public efficacy results sufficient to quantify brenipatide’s weight-loss effect are not yet available.
Primary sources
Eli Lilly Clinical Trials. RENEW-ALC-1: A Study of Brenipatide in Participants With Moderate-to-Severe Alcohol Use Disorder.
Eli Lilly Clinical Trials. RENEW-ALC-2: A Study of Brenipatide in Participants With Alcohol Use Disorder.
Eli Lilly Clinical Trials. RENEW-Smk-1: A Study of Brenipatide in Adults Who Quit Smoking Cigarettes and Want to Avoid Relapse.
ClinicalTrials.gov. A Study of Brenipatide in Healthy Participants With Overweight or Obesity.
Hendershot CS, et al. Once-Weekly Semaglutide in Adults With Alcohol Use Disorder: A Randomized Clinical Trial. JAMA Psychiatry. 2025;82(4):395-405.
National Institute on Alcohol Abuse and Alcoholism. Understanding Alcohol Use Disorder.