No human data · Grade D
Brenipatide
Brenipatide (LY3537031)
Score
52 / 100
Class
Dual agonist · GLP-1 / GIP · monthly
Sponsor
Eli Lilly
Phase
III · RENEW-ALC 1 & 2
TL;DR
01
Eli Lilly's investigational once-monthly dual GLP-1 / GIP receptor agonist, registered on ClinicalTrials.gov as LY3537031 (earlier referenced as LY3843513).
02
Lead indication is novel for the incretin class: alcohol use disorder (AUD) — not obesity or type 2 diabetes. Two parallel Phase 3 trials, RENEW-ALC-1 (NCT07219966) and RENEW-ALC-2 (NCT07219953), together enrolling 2,200 adults across 233 global sites.
03
Builds on preclinical evidence that dual GLP-1/GIP agonism attenuates alcohol's reinforcing and interoceptive effects (tirzepatide in rodents, PMID 41506148 and 40699363), and genetic evidence that GIPR/GLP-1R signaling reduces binge drinking in humans (PMID 40931165).
04
Monthly depot pharmacology is a deliberate adherence bet for addiction care — one shot a month rather than weekly self-administration. Not available outside of the trials; primary completion is April 2028.
Indication
AUD
moderate-to-severe
Trial enrollment
2,200
across both Phase 3 trials
Treatment duration
56 weeks
per RENEW-ALC protocol
Dosing cadence
Monthly SC
novel for class
Primary completion
April 2028
RENEW-ALC-1 & -2
Part 01 · How it works
Mechanism.
Brenipatide activates two gut hormone receptors — GLP-1 and GIP — with a long-acting design that allows once-a-month dosing. The reason Lilly is aiming this at alcohol use disorder is that GLP-1 signaling appears to quiet the same brain reward circuits that drive cravings for food and alcohol. Patients on GLP-1 drugs for diabetes or weight have repeatedly reported drinking less without trying, and animal studies show these receptors sit directly on the dopamine pathways that fire during reward. Brenipatide is the first drug in this class engineered from the ground up to test that hypothesis in a dedicated addiction trial.
Semaglutide and tirzepatide turn down the volume on food. Brenipatide is built on the bet that the same dial turns down the volume on alcohol — and that pushing dosing from weekly to monthly makes it actually usable in addiction treatment, where remembering to take something every day is often the first thing to go.
GLP-1R agonism
Activates GLP-1 receptors in the periphery and CNS. In reward circuits (VTA, nucleus accumbens), GLP-1R signaling has been shown to attenuate dopaminergic response to ethanol in preclinical models.
GIPR agonism
Co-agonism at the GIP receptor; the incremental contribution to AUD-specific endpoints is less well characterized than for metabolic endpoints.
Long-acting pharmacology
Engineered for once-monthly subcutaneous dosing — a major pharmacokinetic departure from weekly GLP-1s and aimed squarely at the adherence problem in addiction care.
Mesolimbic reward circuit
Convergent preclinical evidence that GLP-1R activation reduces ethanol self-administration and craving-like behaviors in rodents and non-human primates.
Translation uncertainty
Class observational evidence in humans is suggestive, but the leap from secondary observations with weekly agents to a dedicated monthly dual agonist is exactly what Phase 3 must establish.
Part 02 · Dosing & administration
How it's taken.
Values below describe how Brenipatide has been administered in published trials and labeling. Provided for educational purposes only — this is not medical advice and not instructions for self-administration. Consult your healthcare provider before making any health decision.
Wk Month 1
Depot 1
Single subcutaneous monthly injection
Wk Month 2
Depot 2
Monthly cadence
Wk Month 3
Depot 3
Monthly cadence
TARGET
Wk Month 4+
Maintenance
Per trial protocol · specific mg not publicly disclosed
·
Trial-protocol only. Specific mg values for each monthly dose are not in the public domain.
·
Monthly depot pharmacology means the first weeks after each injection will see peak exposure and peak likelihood of incretin-class side effects.
·
Because the drug cannot be rapidly cleared between monthly doses, any serious adverse event requires supportive care rather than dose reduction.
Need help with reconstitution?
Use the free peptide calculator for dilution, unit conversion, and injection volume.
Part 03 · Safety
Side effects, rare serious events, who shouldn't.
Common
Nausea
Likely most prominent in the days after each monthly injection; brenipatide-specific rate not yet published.
Class-expected
Vomiting
Monthly peak-exposure window may concentrate GI AEs.
Class-expected
Diarrhea
Typical of GLP-1 / GIP agents.
Class-expected
Decreased appetite
Part of incretin pharmacology; clinically relevant in AUD populations who may have existing nutritional compromise.
Class-expected
Injection-site reactions
Monthly depot formulations tend to produce more local reactions than weekly formulations.
Class-expected
Serious · rare
Pancreatitis
Class concern; AUD population already has elevated pancreatitis risk from alcohol itself.
<1% (class)
Hepatic injury
Background AUD-related liver disease complicates attribution; monitor liver enzymes.
Unknown
Thyroid C-cell tumors
Inherited black-box caution from GLP-1 class.
Rodent signal
Severe GI / gastroparesis
Emerging class signal; monthly dosing kinetics are a novel variable.
Class-expected
Alcohol co-exposure effects
Trial population continues to drink; interaction between heavy alcohol use and peak incretin exposure is a genuinely new safety territory.
Unknown
Absolute · do not use
×
Personal or family history of medullary thyroid carcinoma (class caution inherited from GLP-1 agents)
×
Multiple endocrine neoplasia syndrome type 2 (MEN2) (class caution)
×
Known hypersensitivity to brenipatide or any component
×
History of pancreatitis
×
Pregnancy or breastfeeding
×
Severe gastrointestinal disease (gastroparesis)
×
Use outside of a registered clinical trial (brenipatide is not approved; there is no legitimate supply chain)
Relative · discuss first
!
Severe alcohol-related liver disease (decompensated cirrhosis) — trial exclusions likely apply
!
History of pancreatitis — already a class caution, compounded by AUD-related pancreatic risk
!
Active use of naltrexone, acamprosate, or disulfiram — typically excluded in trials
!
Pregnancy or breastfeeding
!
Severe gastrointestinal disease (gastroparesis)
!
Any attempt to source brenipatide outside of the Lilly trial — no legitimate supply chain exists
Interactions
Alcohol
The target population continues to consume alcohol during the trial. GI side effects of incretin agents may be magnified by concurrent heavy alcohol use; hepatic injury risk may compound.
Major
Naltrexone, acamprosate, disulfiram
Concurrent AUD pharmacotherapy is typically excluded in trials; combined use outside of research has no established safety or efficacy basis
Unknown
Insulin and sulfonylureas
As with other incretin agents, expected additive hypoglycemia risk in any patient with co-existing diabetes
Major
Oral medications with narrow therapeutic index (warfarin, digoxin, levothyroxine)
Delayed gastric emptying (incretin class effect) may alter oral drug absorption; monitor levels appropriately
Moderate
Oral hormonal contraceptives
Delayed gastric emptying may reduce absorption, especially during the initial exposure window of each monthly dose; non-oral contraception may be preferable during trial participation
Moderate
Labs to monitor
Liver panel (AST, ALT, GGT)
Baseline and every 3 months per trial protocol
AUD-related hepatic injury is common; monitor baseline and during treatment
CBC with Differential
Baseline and every 6 months
Screen for alcohol-associated macrocytosis and thrombocytopenia
CMP (Comprehensive Metabolic Panel)
Baseline and every 3 months
Renal function, electrolytes, and incretin-class hepatic/renal monitoring
Lipase
Baseline and if symptomatic
Pancreatitis surveillance (incretin class concern)
Phosphatidylethanol (PEth) or other alcohol biomarker
Per trial protocol
Objective measure of alcohol use alongside self-report
HbA1c and Fasting Glucose
Baseline and every 6 months
Incretin-class glycemic tracking; AUD is associated with metabolic dysregulation
Part 04 · Evidence
How strong is the evidence?
52
Grade D
Grade D reflects the state of public evidence, not the quality of the science. Mechanistic plausibility is solid; class signal is real and consistent. What is missing is any peer-reviewed brenipatide-specific efficacy or safety data. The Phase 3 readout will move this score substantially in either direction.
Mechanistic plausibility
GLP-1 signaling in addiction reward circuits is well-mapped preclinically; GIP's contribution is less clear.
78
Animal data
Rodent GLP-1 / ethanol work is robust and independently replicated; brenipatide-specific preclinical data not in the public domain.
74
Human trial quality
Phase 3 in progress. No peer-reviewed brenipatide Phase 2 or Phase 3 efficacy data published yet.
42
Replication
Zero brenipatide-specific human replication; class-evidence replication exists only for GLP-1-alone agents in secondary AUD endpoints.
30
Safety signal
Presumed incretin-class GI and pancreatitis profile. Monthly depot kinetics and the AUD population introduce genuinely unknown interaction territory.
55
Long-term data
No multi-year data on brenipatide in any population. AUD is a chronic condition — multi-year evidence is what will matter.
32
Part 05 · Research log
Every study we cite.
We list each study with its methodology, funding source, and our quality grade. Flagged studies aren't dismissed — they're tagged so you can weigh them.
01
2025
ClinicalTrials.gov — NCT07219966 Preliminary
RENEW-ALC-1: Phase 3 brenipatide (LY3537031) vs placebo in moderate-to-severe AUD
Recruiting since Oct 15, 2025 across 119 sites. Primary outcome: change in drinking patterns via Timeline Followback (TLFB). Secondary: PACS craving scale, AUDIT, body weight, SF-36, PK Cavg, anti-drug antibodies. Notable site PIs include Lara Ray (UCLA), Henry Kranzler (Penn), Darin Dougherty (Mass General Brigham). Primary completion April 2028.
Phase 3 multicenter double-blind RCT, once-monthly SC dosing, 56-week treatment · n = 1,100 · Industry-sponsored (Eli Lilly). Await peer-reviewed publication; do not rely on interim sponsor communications.
N/A pending readout
02
2025
ClinicalTrials.gov — NCT07219953 Preliminary
RENEW-ALC-2: parallel Phase 3 brenipatide trial in broader AUD population
Recruiting since Oct 16, 2025 across 114 sites. Same intervention (LY3537031) as RENEW-ALC-1 but broader eligibility criteria. Together the two trials enroll 2,200 participants — among the largest dedicated AUD pharmacotherapy programs ever run.
Companion Phase 3 RCT, same intervention, 56-week treatment · n = 1,100 · Same sponsor; two-trial design is standard for pivotal registration programs.
N/A pending readout
03
2025
Molecular Psychiatry (PMID 40931165, DOI 10.1038/s41380-025-03199-3)
Genetic support for GLP-1R and GIPR in alcohol use behaviors — drug-target Mendelian randomization
Genetic proxies for GLP-1R and GIPR activation were associated with reduced binge drinking (β = −0.44, P = 2.4×10⁻³), reduced heavy drinking with psychiatric comorbidity (OR 0.62, P = 0.003), and lower NAFLD/ALT. Individual-locus analyses supported both GIPR and GLP-1R as independently protective — the strongest causal-inference support to date for the dual-target hypothesis brenipatide is built on.
Multi-ancestry Mendelian randomization, NIAAA-led · MR uses genetic variants as lifelong-exposure proxies — not a direct pharmacology readout and not brenipatide-specific.
High (causal inference)
04
2026
EBioMedicine (PMID 41506148, DOI 10.1016/j.ebiom.2025.106119)
Tirzepatide reduces alcohol drinking and relapse-like behaviours in rodents
Dual GLP-1/GIP agonist tirzepatide attenuated alcohol's rewarding properties (locomotor stimulation, conditioned place preference, accumbal dopamine release), dose-dependently reduced voluntary intake, prevented binge and relapse-like drinking, and sustained efficacy with repeated dosing. Also induced synaptic depression in the lateral septum and altered histone regulators — suggesting a plausible neural substrate.
Rodent behavioral, electrophysiology, microdialysis, proteomics · Uses tirzepatide rather than brenipatide; class-level translation is assumed, not proven.
High (preclinical)
05
2025
Psychopharmacology (PMID 40699363, DOI 10.1007/s00213-025-06854-3)
Semaglutide, tirzepatide, and retatrutide attenuate the interoceptive effects of alcohol in rats
Acute administration of all three incretin polyagonists attenuated alcohol's discriminative stimulus effects. Repeated semaglutide maintained efficacy across 15 days; effect reversed three days after cessation. First head-to-head preclinical comparison across GLP-1 mono-, dual-, and triple-agonist designs in an AUD-relevant paradigm.
Operant drug discrimination, male and female rats, acute and repeated dosing · Preclinical and non-brenipatide. Supports the mechanism, not the specific molecule.
High (preclinical)
06
2025
ClinicalTrials.gov — NCT06817356 Preliminary
Lilly's companion program: mazdutide Phase 2 proof-of-concept in AUD (NCT06817356)
Eli Lilly is running a parallel Phase 2 trial of mazdutide (dual GLP-1/glucagon agonist) in AUD, active-not-recruiting since Feb 2025, primary completion Aug 2026. Confirms Lilly's strategic commitment to the AUD indication across multiple incretin molecules rather than a single-molecule bet.
Phase 2, double-blind, placebo-controlled · n = 300 · Different receptor pair (GLP-1/glucagon) and different molecule — portfolio context, not direct brenipatide evidence.
N/A pending readout
Part 06 · Cost & access
Where it's available, at what price.
United States
Investigational
Available only through the Phase 3 RENEW-ALC-1 (NCT07219966) or RENEW-ALC-2 (NCT07219953) trials. The two trials together have 233 global sites — search ClinicalTrials.gov for enrolling locations near you.
No cost within a trial
United Kingdom
Investigational
Confirmed site presence in the RENEW-ALC program (including sites led by Julia Sinclair, Southampton).
No cost within a trial
Belgium · Germany
Investigational
Confirmed EU trial sites in the RENEW-ALC program.
No cost within a trial
Japan · South Korea · Taiwan · China
Investigational
Confirmed Asia-Pacific sites in the RENEW-ALC program.
No cost within a trial
Gray-market / compounded
Not available
We strongly advise against. Brenipatide is a new-entity investigational peptide. Any retail 'brenipatide' is of unverifiable origin and the AUD population is especially poorly served by unverified pharmacotherapy.
N/A
The Peptide Column takes no affiliate commission from any source. For brenipatide, the only legitimate access route is the Phase 3 trial — we will not link to any other source.
Part 07 · Your appointment
Questions to bring.
01
Is there a brenipatide trial site enrolling in my region, and am I eligible given my drinking pattern and medical history?
02
Given that brenipatide is investigational, what FDA-approved AUD medications (naltrexone, acamprosate, disulfiram) should I consider first?
03
How does the monthly-dosing profile affect risk if a problem arises — is there any reversal or washout option?
04
What behavioral treatment is expected alongside any pharmacotherapy for my AUD?