Retatrutide

Summary

Retatrutide (CHEMBL5095485) is a phase-3 clinical-stage protein targeting GIPR, GLP1R, and GCGR; indicated across 4 conditions including diabetes mellitus and obesity disorder.

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Protein
• Targets: 3 (GIPR, GLP1R, GCGR)
• Indications: 4 conditions
• Clinical trials: 32

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL5095485
Name	Retatrutide
Type	Protein
Max phase	3

Also known as: LY-3437943, LY3437943, Retatrutide, RETATRUTIDE

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
GIPR	GIP receptor	Full agonist	10.19	0.2%	P48546
GLP1R	GLP-1 receptor	Full agonist	8.14	0.2%	P43220
GCGR	glucagon receptor	Full agonist	8.24	0.2%	P47871

Bioactivity

No ChEMBL bioactivity rows at pChembl ≥ 5 (expected for biologics / antibodies).

Target pathways

Aggregated over 3 target gene(s): GIPR, GLP1R, GCGR.

Top Reactome pathways

5 total, by targets touching each:

Pathway	Targets	Genes
G alpha (s) signalling events	3	GCGR, GIPR, GLP1R
Glucagon-type ligand receptors	3	GCGR, GIPR, GLP1R
Glucagon signaling in metabolic regulation	1	GCGR
Glucagon-like Peptide-1 (GLP1) regulates insulin secretion	1	GLP1R
G alpha (q) signalling events	1	GCGR

Dominant GO biological processes

GO term	Targets
cell surface receptor signaling pathway	3
adenylate cyclase-activating G protein-coupled receptor signaling pathway	3
signal transduction	3
G protein-coupled receptor signaling pathway	3
generation of precursor metabolites and energy	2
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	2
activation of adenylate cyclase activity	2
positive regulation of cytosolic calcium ion concentration	2
response to nutrient	2
cellular response to glucagon stimulus	2
desensitization of G protein-coupled receptor signaling pathway	1
response to glucose	1
endocrine pancreas development	1
positive regulation of insulin secretion	1
gastric inhibitory peptide signaling pathway	1

Indications & clinical

Indications

4 indications (0 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
diabetes mellitus	3	MONDO:0005015	EFO:0000400
obesity disorder	3	MONDO:0011122	EFO:0001073
type 2 diabetes mellitus	3	MONDO:0005148	MONDO:0005148
kidney failure	1	MONDO:0001106	HP:0000083

Clinical trials

Total trials: 32.

Phase distribution

Phase	Trials
PHASE3	14
PHASE1	14
PHASE2	4

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05882045	PHASE3	ACTIVE_NOT_RECRUITING	A Study of Retatrutide (LY3437943) in Participants With Obesity and Cardiovascular Disease
NCT05929066	PHASE3	ACTIVE_NOT_RECRUITING	A Study of Retatrutide (LY3437943) in Participants Who Have Obesity or Overweight
NCT05929079	PHASE3	ACTIVE_NOT_RECRUITING	A Study of Retatrutide (LY3437943) in Participants With Type 2 Diabetes Mellitus Who Have Obesity or Overweight
NCT06260722	PHASE3	ACTIVE_NOT_RECRUITING	Effect of Retatrutide Compared With Semaglutide in Adult Participants With Type 2 Diabetes and Inadequate Glycemic Control With Metformin With or Without SGLT2 Inhibitor (TRANSCEND-T2D-2)
NCT06297603	PHASE3	ACTIVE_NOT_RECRUITING	Effect of Retatrutide Compared With Placebo in Participants With Type 2 Diabetes and Moderate or Severe Renal Impairment, With Inadequate Glycemic Control on Basal Insulin, With or Without Metformin and/or SGLT2 Inhibitor (TRANSCEND-T2D-3)
NCT06383390	PHASE3	ACTIVE_NOT_RECRUITING	The Effect of Retatrutide Once Weekly on Cardiovascular Outcomes and Kidney Outcomes in Adults Living With Obesity (TRIUMPH-Outcomes)
NCT06662383	PHASE3	ACTIVE_NOT_RECRUITING	A Study of Retatrutide (LY3437943) Compared to Tirzepatide (LY3298176) in Adults Who Have Obesity
NCT06859268	PHASE3	ACTIVE_NOT_RECRUITING	A Study of Retatrutide (LY3437943) in the Maintenance of Weight Reduction in Individuals With Obesity
NCT07035093	PHASE3	RECRUITING	A Study of Retatrutide (LY3437943) in Participants Who Have Obesity or Overweight and Chronic Low Back Pain
NCT07165028	PHASE3	RECRUITING	A Master Protocol of Multiple Agents in Adults With Metabolic Dysfunction-Associated Steatotic Liver Disease (SYNERGY-Outcomes)
NCT07232719	PHASE3	ACTIVE_NOT_RECRUITING	A Study of Retatrutide (LY3437943) in Participants With Obesity or Overweight
NCT07357415	PHASE3	RECRUITING	A Study of Retatrutide (LY3437943) in Participants Without Type 2 Diabetes Who Have Obesity or Overweight
NCT05931367	PHASE3	COMPLETED	A Study of Retatrutide (LY3437943) Once Weekly in Participants Who Have Obesity or Overweight and Osteoarthritis of the Knee
NCT06354660	PHASE3	COMPLETED	Effect of Retatrutide Compared With Placebo in Adult Participants With Type 2 Diabetes and Inadequate Glycemic Control With Diet and Exercise Alone (TRANSCEND-T2D-1)
NCT07467447	PHASE2	RECRUITING	Effect of LY3437943 Versus Placebo in Participants Who Have Obesity or Are Overweight
NCT04867785	PHASE2	COMPLETED	A Study of LY3437943 in Participants With Type 2 Diabetes
NCT04881760	PHASE2	COMPLETED	A Study of LY3437943 in Participants Who Have Obesity or Are Overweight
NCT05936151	PHASE2	COMPLETED	A Study of Retatrutide (LY3437943) on Renal Function in Participants With Overweight or Obesity and Chronic Kidney Disease With or Without Type 2 Diabetes
NCT06982846	PHASE1	ACTIVE_NOT_RECRUITING	A Study to Investigate the Response of Participants With Type 2 Diabetes Mellitus on Once-Weekly Retatrutide to Hypoglycemia
NCT06982859	PHASE1	RECRUITING	A Study to Evaluate the Effect of Retatrutide on Insulin Secretion and Insulin Sensitivity in Adult Participants With Type 2 Diabetes Mellitus
NCT03841630	PHASE1	COMPLETED	A Safety Study of LY3437943 Given as a Single Injection in Healthy Participants
NCT04143802	PHASE1	COMPLETED	A Study of LY3437943 in Participants With Type 2 Diabetes Mellitus (T2DM)
NCT04823208	PHASE1	COMPLETED	A Study of LY3437943 in Japanese Participants With Type 2 Diabetes Mellitus (T2DM)
NCT05445232	PHASE1	COMPLETED	A Drug-Drug Interaction (DDI) Study of LY3437943 in Obese Participants
NCT05548231	PHASE1	COMPLETED	A Study of LY3437943 in Chinese Participants With Obesity Or Overweight
NCT05611957	PHASE1	COMPLETED	A Study of LY3437943 in Healthy Participants and Participants With Impaired Renal Function
NCT05916560	PHASE1	COMPLETED	A Study of LY3437943 in Participants With Impaired and Normal Liver Function
NCT05959096	PHASE1	COMPLETED	A Study of LY3437943 in Healthy Participants With a High Body Mass Index
NCT06003465	PHASE1	COMPLETED	A Research Study Looking at Similarity Between LY3437943 Versions for Different Injection Devices
NCT06039826	PHASE1	COMPLETED	A Study of LY3437943 in Postmenopausal Female Participants Who Are Overweight or Obese
NCT06313528	PHASE1	COMPLETED	A Study to Measure Calorie Consumption and Usage in Participants With Obesity Using LY3437943
NCT06808802	PHASE1	COMPLETED	To Investigate the Effect of Retatrutide (LY3437943) on Metoprolol Pharmacokinetics in Healthy Participants

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No PharmGKB pharmacogenomic data curated for this drug.

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

238 molecules share ≥1 primary target. Top 60 by shared-target count:

Molecule	Source	Status	Shared targets
Dihydroergotamine	ChEMBL + PubChem	Phase 4 (approved)	GCGR, GIPR, GLP1R
GLUCAGON	ChEMBL	Phase 4 (approved)	GCGR, GLP1R
TIRZEPATIDE	ChEMBL	Phase 4 (approved)	GIPR, GLP1R
COTADUTIDE	ChEMBL	Phase 2	GCGR, GLP1R
MK-0893	ChEMBL	Phase 2	GCGR, GIPR
PF-06291874	ChEMBL	Phase 2	GCGR, GLP1R
Aclidinium Bromide	PubChem	Approved	GCGR, GIPR
Acyclovir	PubChem	Approved	GCGR, GIPR
Allopurinol	PubChem	Approved	GCGR, GIPR
Alogliptin	PubChem	Approved	GCGR, GIPR
Bosentan	PubChem	Approved	GCGR, GIPR
Clozapine	PubChem	Approved	GCGR, GIPR
Desloratadine	PubChem	Approved	GCGR, GIPR
Ethambutol	PubChem	Approved	GCGR, GIPR
Fidaxomicin	PubChem	Approved	GCGR, GIPR
Methotrexate	PubChem	Approved	GCGR, GIPR
Olanzapine	PubChem	Approved	GCGR, GIPR
Olmesartan Medoxomil	PubChem	Approved	GCGR, GIPR
Propoxyphene	PubChem	Approved	GCGR, GIPR
Pyrazinamide	PubChem	Approved	GCGR, GIPR
rifampin	PubChem	Approved	GCGR, GIPR
Sildenafil	PubChem	Approved	GCGR, GIPR
Tegaserod	PubChem	Approved	GCGR, GIPR
Tiotropium Bromide Monohydrate	PubChem	Approved	GCGR, GIPR
Valacyclovir	PubChem	Approved	GCGR, GIPR
CANDESARTAN CILEXETIL	ChEMBL + PubChem	Phase 4 (approved)	GIPR
LIRAGLUTIDE	ChEMBL + PubChem	Phase 4 (approved)	GLP1R
ELAGOLIX	ChEMBL	Phase 4 (approved)	GLP1R
EXENATIDE	ChEMBL	Phase 4 (approved)	GLP1R
LOPERAMIDE	ChEMBL	Phase 4 (approved)	GLP1R
PERPHENAZINE	ChEMBL	Phase 4 (approved)	GLP1R
SECRETIN	ChEMBL	Phase 4 (approved)	GLP1R
SEMAGLUTIDE	ChEMBL	Phase 4 (approved)	GLP1R
TOLVAPTAN	ChEMBL	Phase 4 (approved)	GLP1R
ORFORGLIPRON	ChEMBL	Phase 3	GLP1R
ADOMEGLIVANT	ChEMBL	Phase 2	GCGR
DANUGLIPRON	ChEMBL	Phase 2	GLP1R
DEVAZEPIDE	ChEMBL	Phase 2	GLP1R
GLP-1	ChEMBL	Phase 2	GLP1R
LOTIGLIPRON	ChEMBL	Phase 2	GLP1R
MK-3577	ChEMBL	Phase 2	GCGR
Acetylcholine	PubChem	Approved	GIPR
Alendronic Acid	PubChem	Approved	GIPR
Alprazolam	PubChem	Approved	GIPR
Amiloride	PubChem	Approved	GIPR
Amitriptyline	PubChem	Approved	GIPR
Amlodipine	PubChem	Approved	GIPR
Amoxapine	PubChem	Approved	GIPR
Amoxicillin	PubChem	Approved	GIPR
Amphetamine	PubChem	Approved	GIPR
Apomorphine	PubChem	Approved	GIPR
Aripiprazole	PubChem	Approved	GIPR
Aspirin	PubChem	Approved	GIPR
Atorvastatin	PubChem	Approved	GIPR
Azathioprine	PubChem	Approved	GIPR
azithromycin, unspecified form	PubChem	Approved	GIPR
Baclofen	PubChem	Approved	GIPR
Beclomethasone	PubChem	Approved	GIPR
Beclomethasone Dipropionate	PubChem	Approved	GIPR
Benazepril	PubChem	Approved	GIPR