Brenipatide (LY-3537031): Lilly's GIP/GLP-1 Agonist for Addiction, Mood & Asthma

What Is Brenipatide?

Brenipatide (developmental code LY-3537031) is an engineered peptide developed by Eli Lilly and Company. It is a unimolecular dual agonist — a single peptide, not a co-formulation — that simultaneously activates the glucagon-like peptide-1 (GLP-1) receptor and the glucose-dependent insulinotropic polypeptide (GIP) receptor. That puts it in the same receptor class as tirzepatide and distinct from the triple-receptor retatrutide compound, which adds the glucagon receptor.

What makes brenipatide notable is not its receptor target but its indication strategy. Lilly's other incretin peptides are metabolic drugs first. Brenipatide's advanced program — branded RENEW — is built almost entirely around addiction, mood and inflammatory disease: alcohol and opioid use disorder, major depressive disorder, bipolar disorder, schizophrenia, cigarette-smoking relapse and uncontrolled asthma. It is, in effect, the GLP-1-class drug Lilly is steering away from the scale. (Lilly is also running earlier Phase 1 studies in cardiovascular, liver and metabolic disease and obesity, but those are not the late-stage focus.)

Brenipatide is the fourth GLP-1-based molecule Lilly has advanced into late-stage development, joining tirzepatide (Mounjaro/Zepbound), the oral orforglipron, and the triple-agonist retatrutide. For where it sits in the wider incretin landscape, see our GLP-1 / GIP / glucagon mechanism guide.

Mechanism of Action

Brenipatide engages two incretin receptors with a single molecule:

• GLP-1 receptor: The pathway shared by semaglutide and tirzepatide. Beyond appetite and glucose control, GLP-1 receptors are expressed in brain regions that govern reward, motivation and mood, including the mesolimbic dopamine circuit.
• GIP receptor: The second incretin arm, which modulates insulin response and energy handling and is also present in the central nervous system. The GIP component is what brenipatide shares with tirzepatide and what separates it from pure GLP-1 agents.

The reason Lilly is testing an incretin drug in addiction and psychiatry rests on a growing body of GLP-1-class research. In animal and early human studies, GLP-1 receptor agonists have reduced alcohol intake, nicotine and opioid seeking, and other reward-driven behaviours — effects attributed to dampening of dopamine signalling in the brain's reward pathway. We cover that literature in depth in GLP-1, brain reward and addiction cravings. Brenipatide's RENEW program is, in essence, a large, systematic test of whether a long-acting dual incretin can translate those signals into clinical benefit.

The asthma indication draws on a different strand of the same biology: incretin receptor agonism has anti-inflammatory effects, and observational data on GLP-1 drugs has been associated with fewer respiratory exacerbations. Lilly's Phase 2 asthma trial measures whether brenipatide lowers the annualized asthma exacerbation rate.

The mechanisms above describe the published pharmacology of the incretin class and the rationale Lilly has put into trials. Brenipatide-specific mechanistic and efficacy data for each indication has not yet been released. Nothing here is a treatment claim.

What Makes Brenipatide Different

Two features set brenipatide apart from Lilly's metabolic incretins.

1. A longer half-life and monthly dosing. A December 2025 peer-reviewed review of therapeutic-peptide design (Østergaard, Expert Opinion on Drug Discovery) describes brenipatide as a once-monthly dual GLP-1R/GIPR peptide that exhibits a longer elimination half-life than tirzepatide or retatrutide. The review attributes this to a backbone optimized for stability against enzymatic degradation — including a tryptophan-to-α-methyl-tyrosine (Trp→αMe-Tyr) substitution — paired with a single C20 diacid for albumin binding. In plain terms: the molecule is built to last longer in circulation, which supports a once-a-month injection rather than the weekly cadence of tirzepatide and retatrutide. A monthly schedule is a meaningful practical advantage in chronic psychiatric and addiction care, where adherence is a central challenge.

2. A non-metabolic flagship. Brenipatide is the rare incretin whose lead program ignores weight loss. Most GLP-1/GIP development chases obesity and diabetes; brenipatide's Phase 2/3 trials are concentrated in substance-use disorders, mood and psychotic disorders, and asthma. Where metabolic effects do appear — for example, the schizophrenia trial's primary endpoint is body-weight change in overweight participants — they are framed around the metabolic burden of existing psychiatric treatment rather than obesity as a standalone target.

The RENEW Program — Trial Pipeline

Brenipatide's clinical footprint is organised under the RENEW banner. As of June 2026 it spans two Phase 3 indications and six Phase 2 indications, all double-blind and placebo-controlled, plus Phase 1 pharmacology work. The table below is verified against ClinicalTrials.gov records.

Reading the design. The depression and bipolar trials are relapse-prevention studies — brenipatide is added to standard of care and the question is whether it delays time to relapse rather than treating an acute episode. The opioid trial layers brenipatide on top of buprenorphine, the existing standard of care. The schizophrenia trial's weight endpoint targets the metabolic side-effect burden of antipsychotics. Across the board, brenipatide is being positioned as an adjunct, not a replacement for established treatment.

Why an Incretin Drug for Addiction and Mood?

The idea of using a GLP-1-class drug outside metabolism is not new, and it is the single biggest reason brenipatide is interesting. GLP-1 receptors sit in the same brain circuits that drive craving and reward. Over the past several years, signals have accumulated that GLP-1 receptor agonists may blunt the urge to drink, smoke or use opioids — first in rodent models, then in retrospective analyses of people taking semaglutide and tirzepatide for diabetes or obesity, who showed lower rates of alcohol-related and substance-related events.

What has been missing is a large, prospective, placebo-controlled test designed specifically for these endpoints, with a molecule engineered for the job. That is what brenipatide's RENEW program provides: dedicated Phase 3 trials in alcohol use disorder and depression, and Phase 2 trials in opioid use disorder, smoking, bipolar disorder and schizophrenia. If the readouts are positive, brenipatide would be among the first incretins validated for a psychiatric or addiction indication — a genuinely new category. If they are negative, they will be the most rigorous evidence yet on the limits of the GLP-1-for-addiction hypothesis. Our explainer on GLP-1, brain reward and addiction walks through the underlying neuroscience.

How It Compares — Brenipatide vs Tirzepatide vs Retatrutide

All three are Eli Lilly incretin peptides, but they differ in receptor target, dosing and purpose. Brenipatide shares tirzepatide's GIP/GLP-1 receptor pair; retatrutide adds a third (glucagon) receptor. Brenipatide's monthly dosing and addiction/psychiatry focus are the outliers.

For the metabolic side of the family, see our retatrutide vs tirzepatide vs CagriSema comparison and the best obesity drug 2026 overview. Brenipatide is the member of the group that deliberately steps outside that race.

Safety, Efficacy & What's Known So Far

As of June 2026, no Phase 2 or Phase 3 efficacy results for brenipatide have been published, and no peer-reviewed safety dataset is available. Every RENEW trial is still recruiting or treating, with the earliest primary completion (smoking relapse) due in February 2027. Any specific efficacy figure circulating before then would not be supported by primary-source data — and this profile deliberately does not quote one.

What can reasonably be inferred is class context. As a GIP/GLP-1 peptide, brenipatide would be expected to carry the gastrointestinal tolerability profile typical of the incretin class — nausea, reduced appetite and related effects that tend to be dose- and titration-dependent. Whether brenipatide's monthly, long-acting design changes that profile is an open question its trials are designed to answer. Until Lilly releases data, treat brenipatide's risk–benefit as undetermined.

For live status tracking as readouts arrive, this profile will be updated; related Lilly pipeline trackers include Is retatrutide approved? and the orforglipron profile.

Research Use Notes

Brenipatide is not available through Remy Peptides, and it is not available for purchase anywhere. The compound is proprietary to Eli Lilly, is only administered inside controlled clinical trials, and is not distributed as a reference standard through research-supply channels. Any product marketed as "brenipatide" or "LY-3537031" outside Lilly's trials should be treated as unverified.

Researchers studying dual-incretin pharmacology generally work with published literature and class-adjacent reference compounds. Remy Peptides supplies HPLC-verified retatrutide pens (Janoshik Analytical Batch RETP002, 99.262% purity) as its anchor incretin reference for in-vitro laboratory research. Retatrutide shares brenipatide's GLP-1 and GIP arms and adds glucagon, making it a useful bench reference for laboratories characterising incretin-receptor pharmacology. For full laboratory context, see our retatrutide in Dubai research guide.

All Remy Peptides products are supplied for in-vitro laboratory research only. Not for human or veterinary use. UAE MoHAP Circular 17/2022 compliance statement.