Published findings, in context.

Isolated human right atrial preparations: force of contraction and its pharmacological modulation

“Inotropic effects of retatrutide in isolated human atrial preparations.”

Neumann J, Ahlrep U, Hofmann B, Gergs U·Naunyn-Schmiedeberg's Archives of Pharmacology·2026·PMID 40613938 (opens PubMed in a new tab)·DOI 10.1007/s00210-025-04421-3 (opens the publisher record in a new tab)

Filed under GLP-3

Model

Right atrial preparations obtained during cardiac surgery from 29 patients (24 men and 5 women, aged 52–84); isometric force measurement under electrical stimulation in an organ bath

Sample size

29

Exposure

Retatrutide added to the isolated tissue at increasing concentrations, with and without a phosphodiesterase-3 inhibitor (cilostamide)

Comparator

Force of contraction before exposure; selective antagonists of the peptide's three receptors; propranolol, carbachol, stimulation of adenosine A1 receptors and ryanodine

Study by an academic group without affiliation to the developer. In isolated human right atrial preparations, retatrutide increased force of contraction in a concentration- and time-dependent manner; with the phosphodiesterase-3 inhibitor cilostamide present, the effect was larger and relaxation time shortened. The effect was reduced by selective antagonists of its three receptors and by carbachol, stimulation of adenosine A1 receptors and ryanodine, but not by propranolol; the authors interpret it as a cAMP-mediated action through those receptors rather than through β-adrenergic receptors. The sinus node and ventricular tissue were not examined.

Systematic review of 36 studies (35 preclinical, 1 in humans): mechanism, musculoskeletal endpoints, biotransformation and safety

“Emerging Use of BPC-157 in Orthopaedic Sports Medicine: A Systematic Review.”

Vasireddi N, Hahamyan H, Salata MJ et al.·HSS Journal·2025·PMID 40756949 (opens PubMed in a new tab)·DOI 10.1177/15563316251355551 (opens the publisher record in a new tab)

Filed under BPC-157

Model

Systematic review (PubMed, Cochrane, Embase; through June 2024) of studies on mechanism, musculoskeletal outcomes, biotransformation and safety

Of 544 records identified, 36 studies were included (35 preclinical and 1 in humans). The authors synthesize functional, structural and biomechanical measures from preclinical musculoskeletal models, together with GHR expression and inflammatory cytokine levels; the only study in humans was retrospective. No human safety data were found, and the evidence was graded as level IV and V.

Uncontrolled pilot study in 2 adults: blood markers and vital signs at baseline and after exposure

Lee E, Burgess K·2025·PMID 40131143 (opens PubMed in a new tab)Full record on PubMed

Filed under BPC-157

Model

Uncontrolled pilot study at a private clinic in 2 adults (aged 58 and 68), both exposed to the peptide before the study; blood markers and vital signs recorded at baseline and after each exposure

Sample size

2

Exposure

BPC-157; single arm

Comparator

No control group

Blood markers of heart, liver, kidney and thyroid function and vital signs were recorded at baseline and after each exposure, and the participants were asked about adverse events at each visit. With two participants, both previously exposed to the peptide, and no control group or blinding, the study cannot characterize safety; its result is not summarized in this profile.

Single-arm open-label pilot study: symptom questionnaire in 12 women with interstitial cystitis

“Effect of BPC-157 on Symptoms in Patients with Interstitial Cystitis: A Pilot Study.”

Lee E, Walker C, Ayadi B·2024·PMID 39325560 (opens PubMed in a new tab)Full record on PubMed

Filed under BPC-157

Model

Single-arm, open-label pilot study at a private clinic in 12 women aged 39–76 with moderate to severe interstitial cystitis

Sample size

12

Exposure

BPC-157 (compounded preparation); single arm

Comparator

No control group

Symptoms were assessed with the Global Response Assessment questionnaire; the authors report responses from all 12 participants and no dropouts. Because this was an open-label pilot study without a control group or blinding and with a subjective outcome, its design does not allow any change to be attributed to the peptide. The self-rated result is not summarized in this profile.

Randomized, double-blind, placebo-controlled 48-week trial in 338 adults: endpoints not summarized in this profile

The New England Journal of Medicine·2023·PMID 37366315 (opens PubMed in a new tab)Full record on PubMed·DOI 10.1056/NEJMoa2301972 (opens the publisher record in a new tab)

Filed under GLP-3

Model

Randomized, double-blind, placebo-controlled trial of 48 weeks in 338 adults, with several exposure groups and a placebo group; registered as NCT04881760

Sample size

338

Exposure

Retatrutide, several exposure groups

Comparator

Placebo

Trial funded by the developer, with company employees among the authors, conducted with material supplied by the developer. Its primary and secondary endpoints are not summarized in this profile; they are described in the original record. The authors report that the most common adverse events were gastrointestinal, occurred more often in higher-exposure groups and were mostly mild to moderate, and that heart rate increased with exposure, peaking at 24 weeks and declining thereafter.

Rat quadriceps detachment model: defect size, function, muscle histology and nitric oxide markers

Japjec M, Horvat Pavlov K, Petrovic A et al.·Biomedicines·2021·PMID 34829776 (opens PubMed in a new tab)Title on PubMed·DOI 10.3390/biomedicines9111547 (opens the publisher record in a new tab)

Filed under BPC-157

Model

Surgical detachment of the quadriceps muscle in the rat; assessment at days 7, 14, 28 and 42

Exposure

BPC-157 vs no-peptide controls

Comparator

Controls without peptide

In a rat model of surgical detachment of the quadriceps muscle, the BPC-157 and control groups were compared on defect size, function, muscle atrophy, inflammatory infiltrate and the orientation of the junction tissue from day 7 to day 42, together with eNOS and COX-2 mRNA, oxidative stress and nitric oxide levels; the direction and size of these differences are not summarized in this profile.

Retrospective chart review with a telephone survey: self-reported knee pain in 16 people, no control group

Lee E, Padgett B·2021·PMID 34324435 (opens PubMed in a new tab)Full record on PubMed

Filed under BPC-157

Model

Retrospective chart review (2019–2020) with a telephone survey at a private clinic; people with knee pain of various causes

Sample size

16

Exposure

BPC-157 as recorded in the charts; 4 of the 16 charts also record a second peptide

Comparator

No control group

Of 17 people on record, 16 were reached by telephone 6 months to 1 year later and asked about their knee pain. There was no control group or blinding, the outcome was self-reported, and the abstract does not report imaging or validated function or quality-of-life instruments; the design carries a high risk of selection and recall bias and does not allow any change to be attributed to the peptide. The self-reported result is not summarized in this profile.

Isolated rat aorta and cultured endothelial cells: vasomotor tone and Src–caveolin-1–eNOS signaling

“Modulatory effects of BPC 157 on vasomotor tone and the activation of Src-Caveolin-1-endothelial nitric oxide synthase pathway.”

Hsieh MJ, Lee CH, Chueh HY et al.·Scientific Reports·2020·PMID 33051481 (opens PubMed in a new tab)·DOI 10.1038/s41598-020-74022-y (opens the publisher record in a new tab)

Filed under BPC-157

Model

Ex vivo rat aortic rings with and without endothelium; 3D vascular smooth muscle cell model; cultured endothelial cells

Exposure

BPC-157 vs no-peptide preparations (ex vivo and in vitro)

Comparator

Preparations without peptide; L-NAME, hemoglobin, Src inhibitor

In isolated rat aorta, concentration-dependent vasodilation was observed that was attenuated in the absence of endothelium and inhibited by L-NAME or hemoglobin, indicating a nitric oxide-dependent mechanism. In endothelial cells, nitric oxide generation and phosphorylation of Src, caveolin-1 and eNOS increased and were abolished by a Src inhibitor, with less caveolin-1/eNOS association in co-immunoprecipitation assays. No direct relaxant effect on smooth muscle cells was seen in the 3D model.

Rat hippocampal ischemia/reperfusion model: neuronal damage, behavioral tests and hippocampal gene expression

Vukojević J, Vrdoljak B, Malekinušić D et al.·Brain and Behavior·2020·PMID 32558293 (opens PubMed in a new tab)Title on PubMed·DOI 10.1002/brb3.1726 (opens the publisher record in a new tab)

Filed under BPC-157

Model

Ischemia/reperfusion by bilateral clamping of the common carotid arteries (20 min) in male rats; assessment at 24 and 72 h

Exposure

BPC-157 vs saline

Comparator

Saline

In rats subjected to cerebral ischemia/reperfusion, hippocampal expression of Egr1, Akt1, Kras, Src, Foxo, Srf, Vegfr2, Nos3 and Nos1 was higher, and that of Nos2 and Nfkb lower, in the BPC-157 group than in saline controls; Mapk1 was not activated. Early and late hippocampal neuronal damage and performance on memory (Morris water maze), locomotion and coordination tests were also assessed; their direction is not summarized in this profile. Exploratory findings in an animal model.

Critical narrative review of preclinical studies in rodent muscle and connective-tissue models

Gwyer D, Wragg NM, Wilson SL·Cell and Tissue Research·2019·PMID 30915550 (opens PubMed in a new tab)Title on PubMed·DOI 10.1007/s00441-019-03016-8 (opens the publisher record in a new tab)

Filed under BPC-157

Model

Critical narrative review of preclinical studies in rodent muscle and connective-tissue models

Critical review by an independent group (Loughborough University) of the preclinical literature in small rodent models of muscle and connective-tissue lesions. It notes that only a handful of research groups had studied the peptide in depth, that the effects reported in rodents had yet to be confirmed in humans and that the precise mechanisms still needed to be understood.

Rat hindlimb ischemia model, chick chorioallantoic membrane and HUVEC: VEGFR2 expression and Akt–eNOS signaling

Hsieh MJ, Liu HT, Wang CN et al.·Journal of Molecular Medicine (Berlin)·2017·PMID 27847966 (opens PubMed in a new tab)Title on PubMed·DOI 10.1007/s00109-016-1488-y (opens the publisher record in a new tab)

Filed under BPC-157

Model

Rat hindlimb ischemia (laser Doppler, histology); chorioallantoic membrane (CAM) assay; tube formation in HUVEC

Exposure

BPC-157 vs no-peptide controls (ischemia model and in vitro systems)

Comparator

Controls without peptide; blockade with dynasore (endocytosis inhibitor)

In HUVEC, VEGFR2 mRNA and protein increased (VEGF-A did not), with internalization of the receptor, time-dependent activation of the VEGFR2–Akt–eNOS pathway and greater tube formation; these effects were suppressed by the endocytosis inhibitor dynasore. Vascular density in the chorioallantoic membrane assay, and blood flow (laser Doppler), vessel counts and vascular VEGFR2 in rats with hindlimb ischemia, were also measured; the direction and size of these in vivo endpoints are not summarized in this profile.

Rat cutaneous alkali-burn model and HUVEC: burned-skin histology, tissue VEGF and endothelial ERK1/2 signaling

Huang T, Zhang K, Sun L et al.·2015·PMID 25995620 (opens PubMed in a new tab)Full record on PubMed·DOI 10.2147/DDDT.S82030 (opens the publisher record in a new tab)

Filed under BPC-157

Model

Cutaneous alkali burn in the rat, with histological assessment at day 18; cultured human endothelial cells (HUVEC) and NIH 3T3 fibroblasts

Exposure

BPC-157 vs no-peptide control (rat model and cell cultures)

Comparator

Model control group without peptide

In a rat cutaneous alkali-burn model, the BPC-157 and control groups were compared on the size of the burned area, granulation tissue, re-epithelialization, extracellular matrix deposition and tissue VEGF; the direction and size of these endpoints are not summarized in this profile. In HUVEC, greater proliferation, migration and tube formation were described, with regulation of ERK1/2 phosphorylation and of c-Fos, c-Jun and Egr-1 expression; these cell findings refer to HUVEC, not to the NIH 3T3 cells also used. Study by a group independent of the originating group.

Rat Achilles-derived fibroblasts: GHR gene and protein expression, proliferation and JAK2 signaling

Chang CH, Tsai WC, Hsu YH et al.·Molecules·2014·PMID 25415472 (opens PubMed in a new tab)Title on PubMed·DOI 10.3390/molecules191119066 (opens the publisher record in a new tab)

Filed under BPC-157

Model

Primary fibroblasts isolated from rat Achilles; cDNA microarray, quantitative PCR, Western blot

Exposure

BPC-157, with and without subsequent GHR-ligand stimulation, vs no-peptide culture

Comparator

Culture without peptide

Microarray analysis identified GHR among the most strongly induced genes in Achilles-derived fibroblasts exposed to the peptide; the concentration- and time-dependent increase was confirmed at the mRNA and protein levels. Subsequent stimulation of pre-exposed cells with the GHR ligand was associated with greater proliferation (MTT, PCNA) and JAK2 activation. In vitro observation whose in vivo relevance was not assessed.

Rat Achilles explants and Achilles-derived fibroblasts: outgrowth, survival, migration and FAK–paxillin signaling

Chang CH, Tsai WC, Lin MS et al.·Journal of Applied Physiology·2011·PMID 21030672 (opens PubMed in a new tab)Title on PubMed·DOI 10.1152/japplphysiol.00945.2010 (opens the publisher record in a new tab)

Filed under BPC-157

Model

Explant cultures of rat Achilles and primary rat Achilles-derived fibroblasts

Exposure

BPC-157 vs no-peptide culture

Comparator

Culture without peptide

In rat Achilles explants, cell outgrowth was faster; fibroblast proliferation (MTT) did not change, but survival under H2O2 stress, transwell migration and cell spreading increased in a concentration-dependent manner, with F-actin formation and higher FAK and paxillin phosphorylation and no change in total protein. The authors propose the FAK–paxillin pathway as a mechanistic hypothesis.

Rat Achilles transection model and cultured tenocytes: biomechanical, functional and histological endpoints

Staresinic M, Sebecic B, Patrlj L et al.·Journal of Orthopaedic Research·2003·PMID 14554208 (opens PubMed in a new tab)Title on PubMed·DOI 10.1016/S0736-0266(03)00110-4 (opens the publisher record in a new tab)

Filed under BPC-157

Model

Complete Achilles tenotomy in the rat; cultured tenocytes exposed to 4-hydroxynonenal

Exposure

BPC-157 vs saline vehicle

Comparator

Saline

After complete Achilles tenotomy in rats, the BPC-157 and saline groups were compared on biomechanical measures (load to failure, Young's modulus), the Achilles functional index, the size of the macroscopic defect and histology (inflammatory cells, fibroblasts, reticulin and fibrillar extracellular matrix); the direction and size of the differences are not summarized in this profile. In cultured tenocytes, the peptide alone did not change growth but counteracted the growth inhibition caused by the aldehyde 4-hydroxynonenal.

Rat gastric and duodenal lesion models (restraint stress, cysteamine, ethanol): lesion counts and mucosal endothelium

Sikiric P, Seiwerth S, Grabarevic Z et al.·Life Sciences·1994·PMID 7904712 (opens PubMed in a new tab)Title on PubMed·DOI 10.1016/0024-3205(94)00796-9 (opens the publisher record in a new tab)

Filed under BPC-157

Model

Rat models of gastric and duodenal lesions (restraint stress, cysteamine, 96% ethanol)

Exposure

BPC-157 vs reference agents

Comparator

H2 receptor antagonists (famotidine, cimetidine), dopaminergic agents and gut peptides (including somatostatin, neuropeptide Y, secretin and cholecystokinin)

In three rat models of gastric and duodenal lesions, mucosal lesions were counted after BPC-157 and after each of the reference agents, and Monastral blue labeling was used to examine the mucosal endothelium. The authors report differences between BPC-157 and the reference agents; their direction and size are not summarized in this profile. Early primary study in an animal model.

Narrative review by the originating group: the BPC 157 fragment and its early rat lesion models

Sikirić P, Petek M, Rucman R et al.·Journal of Physiology, Paris·1993·PMID 8298609 (opens PubMed in a new tab)Title on PubMed·DOI 10.1016/0928-4257(93)90038-u (opens the publisher record in a new tab)

Filed under BPC-157

Model

Narrative review by the originating group of its own preclinical work

Early overview by the originating group of its own work. It refers back to the group's isolation of a gastric juice peptide (BPC, Mr about 40,000), presents the fully characterized 15-amino-acid fragment BPC 157, which the authors consider essential for the activity they studied, and sets out their hypothesis that the stomach mediates responses to stress in other organs. It summarizes the group's lesion models in several organs and proposes the peptide as a possible endogenous mediator.