Apelin-13

Also known as (Pyr1)apelin-13 · Pyr-apelin-13 · Pyroglutamyl apelin-13 · APJ receptor agonist peptide · Apelin fragment 65-77 · APLN-13

Not approved — research use onlyBLimited human data What this means

Apelin-13 is a 13-residue fragment of the endogenous apelin peptide and an agonist at the APJ (apelin) receptor; short randomized human infusion studies report vasodilatation, increased cardiac output and an insulin-sensitising effect, while most disease-level evidence is from cells and rodents and no approved use exists.

US status: Not approved — research use only
Evidence: Grade B
Half-life: Not located as a numeric value in the sources reviewed. Rapid plasma clearance is described as a limitation that motivates delivery work such as microneedle patches ^5.
Class: Endogenous peptide fragment and APJ (apelin receptor) agonist

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Dosing reference Cycle-length evidence

Unbranded reference vial illustrating Apelin-13; not an actual product

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Key takeaways

Apelin-13 is a C-terminal fragment of the endogenous peptide apelin and an agonist at the APJ receptor, identified in 1998 ^6.
Short randomized, placebo-controlled human infusion studies report peripheral and coronary vasodilatation and increased cardiac output, with the forearm response preserved in chronic heart failure where the acetylcholine response was attenuated ^1.
A randomized crossover clamp study in 16 healthy overweight men reported improved insulin sensitivity at the higher of two levels tested, with no side effects reported on cardiovascular monitoring ^2.
Disease-level evidence is preclinical and mixed: rodent models report protection in neonatal brain injury, doxorubicin cardiac injury and renal ischaemia-reperfusion, while a 2026 study reported that apelin-13 drove vascular smooth muscle proliferation and atherosclerosis ^4,8,9,10.
No approved use exists, rapid clearance is a recognised obstacle, and two papers on apelin-13 and foam cells have been retracted ^5,11,13.

Development stage

Where Apelin-13 sits between laboratory work and regulatory approval.

Preclinical
Animal and cell work
Phase 1 (current)
First human safety studies
Phase 2
Early efficacy signal
Phase 3
Confirmatory trials
Approved
Cleared by a regulator

Stage comes from the regulatory record and ClinicalTrials.gov studies naming the compound (for compounds approved nowhere, only completed trials or trials with posted results count) (checked 2026-10-24). A registered trial is not a result.

Mechanism of action

Apelin-13 acts on APJ, a G protein-coupled receptor, as an agonist ⁶. The receptor and its ligand are expressed in vasculature, heart, kidney, adipose tissue and brain, which is why the reported effects span several organ systems ^1,2.

Cardiovascular actions in people

In human studies, intrabrachial (Pyr1)apelin-13 produced forearm vasodilatation in both patients with heart failure and controls; an intracoronary bolus of apelin-36 increased coronary blood flow and the maximum rate of rise in left ventricular pressure and reduced peak and end-diastolic left ventricular pressures; and systemic (Pyr1)apelin-13 infusion raised cardiac index while lowering mean arterial pressure and peripheral vascular resistance ¹.

Metabolic actions

Apelin is described as an adipokine, and in rodents it improves glucose tolerance and insulin sensitivity; in a human clamp study, intravenous (Pyr1)apelin-13 raised the glucose infusion rate required to maintain euglycaemia at the higher of two levels tested, which the authors presented as the first demonstration of an insulin-sensitising action in people ².

Signalling reported in preclinical models

Neuroprotection: AMPK activation with reduced neuroinflammation in neonatal rat hypoxic-ischaemic brain injury ⁴, and APJ/mTORC2 signalling in microglia after intracerebral haemorrhage in mice.
Cardiac and renal: PI3K/AKT and ERK/MAPK signalling in doxorubicin myocardial injury, and attenuated fibrotic remodelling after renal ischaemia-reperfusion in aged animals ^8,9.
Muscle: stimulation of mitochondrial biogenesis and myofibre regeneration is the stated rationale for sarcopenia work, where repeated microneedle delivery improved fibre cross-sectional area and grip strength in aged mice relative to controls ⁵.
Vascular, opposite direction: one 2026 study reported apelin-13 driving vascular smooth muscle cell proliferation and atherosclerosis through disrupted ER-mitochondria coupling and a glycolytic shift ¹⁰.

Biased agonism

Because APJ signals through both G protein and beta-arrestin pathways, biased agonists have been designed and one has been taken into a first-in-human vascular study, a line of work that treats native apelin-13 as the comparator rather than the candidate ⁷.

Molecular structure

PubChem CID 25078060 ↗

2D depiction generated from the PubChem record. Depictions are schematic and do not show salt form, counter-ions or conformation.

Formula: C69H111N23O16S
Molecular weight: 1550.8 g/mol
CAS: 217082-58-1
InChIKey: XXCCRHIAIBQDPX-PEWBXTNBSA-N

Research overview

Human research

Human evidence is short-term and mechanistic. A series of randomized, double-blind, placebo-controlled studies enrolled 18 patients with New York Heart Association class II to III chronic heart failure, 6 patients undergoing diagnostic coronary angiography and 26 healthy volunteers, with measurements by venous occlusion plethysmography, Doppler flow wire and quantitative coronary angiography, pressure wire and thoracic bioimpedance; intrabrachial (Pyr1)apelin-13 caused forearm vasodilatation in patients and controls, vasodilatation to acetylcholine but not to apelin was attenuated in heart failure, intracoronary apelin-36 improved coronary flow and left ventricular pressure measures, and systemic (Pyr1)apelin-13 increased cardiac index and lowered mean arterial pressure and peripheral vascular resistance, raising heart rate only in controls ^1. A randomized, double-blind, placebo-controlled crossover study in healthy overweight men used two sequential groups of 8 participants each and two hyperinsulinaemic-euglycaemic clamps per volunteer; the higher of the two levels tested significantly improved insulin sensitivity, the lower level showed a borderline change, and no side effects were identified on cardiovascular monitoring and safety reporting ^2. A further phase 1 study in type 2 diabetic volunteers (NCT02724566, 9 participants) is listed as completed, following an earlier phase 1 study in overweight volunteers ^3. Separately, a designed biased apelin receptor agonist has been through a first-in-human vascular study ^7. No trial with clinical outcomes was located for apelin-13 itself.

Animal research

Rodent work is extensive and recent. In neonatal rats with hypoxic-ischaemic brain damage, apelin-13 was associated with reduced neuroinflammation and improved neurological function via AMPK activation ^4. In aged mice with sarcopenia, repeated microneedle-patch delivery of Pyr-apelin-13 improved muscle fibre cross-sectional area and grip strength relative to controls, with increased mitochondrial DNA content, comparable to intraperitoneal injection on the same schedule, while a less frequent schedule produced non-significant trends; the study was conducted by the patch developer ^5. Other models report attenuated doxorubicin-induced myocardial injury via PI3K/AKT and ERK/MAPK signalling ⁸ and reduced renal fibrotic remodelling after ischaemia-reperfusion injury in aged animals ^9. A 2026 study in the opposite direction reported that apelin-13 promoted vascular smooth muscle cell proliferation and atherosclerosis ^10.

In-vitro research

Apelin was identified by measuring extracellular acidification in cells expressing the APJ receptor, and synthetic C-terminal fragments of preproapelin activated those cells across a nanomolar to sub-nanomolar range ^6. Cell work in the disease models above describes APJ-linked signalling through AMPK, PI3K/AKT, ERK/MAPK and mTOR pathways ^4,8. Two earlier cell papers reporting that apelin-13 impeded foam cell formation through an autophagic pathway have been retracted ^11.

Key studies

Japp et al., Circulation (2010)
Series of randomized, double-blind, placebo-controlled infusion studies with invasive and non-invasive haemodynamic measurement
Model: Humans (18 patients with chronic heart failure, 6 undergoing coronary angiography, 26 healthy volunteers)
Intrabrachial (Pyr1)apelin-13 caused forearm vasodilatation in patients and controls and was not attenuated in heart failure, unlike acetylcholine; systemic infusion increased cardiac index and lowered mean arterial pressure and peripheral vascular resistance, raising heart rate only in controls.
Gourdy et al., Diabetes Obes Metab (2018)
Randomized, double-blind, placebo-controlled crossover study with hyperinsulinaemic-euglycaemic clamps, two sequential level groups of 8 participants
Model: Humans (16 healthy overweight men)
The higher level tested significantly improved insulin sensitivity by glucose infusion rate, the lower level showed a borderline change, and no side effects were identified on cardiovascular monitoring and safety reports.
Tatemoto et al., Biochem Biophys Res Commun (1998)
Ligand isolation by extracellular acidification screening with cDNA sequencing of the precursor
Model: Laboratory (bovine stomach extracts, APJ-expressing cells)
Isolated apelin as the endogenous APJ receptor ligand from a 77-residue preproprotein, with synthetic C-terminal fragments activating APJ-expressing cells.
Miao et al., Int Immunopharmacol (2026)
Controlled animal study of hypoxic-ischaemic brain damage with neurological function testing and pathway analysis
Model: Animals (neonatal rats)
Apelin-13 was associated with attenuated neuroinflammation and improved neurological function, attributed to AMPK activation.
Kokotidou et al., Sci Rep (2026)
Preclinical evaluation of transdermal microneedle delivery versus intraperitoneal injection and controls, comparing two administration schedules; conducted by the patch developer
Model: Animals (aged mice with sarcopenia)
Repeated microneedle delivery improved muscle fibre cross-sectional area and grip strength relative to controls, with increased mitochondrial DNA content; a less frequent schedule produced non-significant trends.
Life Sci (2026) vascular study (2026)
Experimental vascular study with mechanistic pathway analysis
Model: Cells and animals (vascular smooth muscle, atherosclerosis model)
Reported that apelin-13 promoted vascular smooth muscle cell proliferation and atherosclerosis through REEP5-dependent disruption of ER-mitochondria coupling and a glycolytic shift, a direction opposite to protective claims.

Published adverse-event data

Reported in the cited trials or product labels. Frequencies apply to the stated population and do not transfer to other settings.

Emerging safety signals

Human exposure in the sources reviewed is limited to short infusions. In the clamp study, cardiovascular monitoring and safety reporting revealed no side effect of administration in 16 healthy overweight men; the study was not designed to detect uncommon or delayed events ^2. ² (2018)
Haemodynamic effects are real and measurable in people: systemic infusion lowered mean arterial pressure and peripheral vascular resistance and raised cardiac index in patients and controls, which is relevant for anyone on blood-pressure-lowering treatment ^1. ¹ (2010)
Preclinical direction of effect is not settled in vascular disease; one 2026 study reported pro-atherosclerotic effects, and two earlier papers reporting anti-foam-cell effects have been retracted ^10,11. ¹⁰ (2026)

What is not known: No clinical outcome trial of apelin-13 was located; human studies measure physiology over minutes to hours, not clinical endpoints ^1,2,3. Half-life has not been located as a numeric value, and rapid plasma clearance is described as the central obstacle to use, which is why delivery systems are being developed ^5. Whether the insulin-sensitising finding in 16 overweight men generalises, and whether it persists beyond an infusion, is untested ^2. The direction of effect in atherosclerosis is contested, with retracted literature in this area ^10,11. Long-term safety, immunogenicity and effects of repeated exposure are unaddressed in the sources reviewed.

Background viewing

We haven't found a clinician video focused on Apelin-13 yet. Meanwhile, this widely watched talk covers the science of aging in general. It does not discuss Apelin-13.

David Sinclair, PhD (Harvard Medical School) on the biology of aging

The Diary Of A CEO · 6.9M views · 2026

These creators are not affiliated with Amiravo and do not endorse Amiravo or any product linked on this site. Nothing here is medical advice. Video views counted on YouTube as of Oct 24, 2026.

Regulatory status

Status: Not approved for any use. An openFDA Drugs@FDA query for apelin returned no application record on 24 October 2026 ^13, and apelin does not appear in any of the three categories of FDA's 503A bulk drug substances list as updated May 14, 2026 ^14. Human work consists of short mechanistic infusion studies, not treatment trials with clinical endpoints ^1,2,3.
United States (FDA): Not approved for any use. An openFDA Drugs@FDA query for apelin returned no application record on 24 October 2026 ^13, and apelin does not appear in any of the three categories of FDA's 503A bulk drug substances list as updated May 14, 2026 ^14.
Sport (WADA): Not named individually in the sources reviewed; S0 covers substances without governmental approval for human therapeutic use, prohibited at all times ^15.

Status varies by country and changes over time. How we describe regulatory status.

Quality and testing notes

A certificate of analysis should state which apelin species the material is: apelin-13, the pyroglutamyl form (Pyr1)apelin-13, apelin-17 or apelin-36 are different molecules with different stability, and human studies used the pyroglutamyl form or apelin-36 depending on the experiment [1, 2]. Expect identity by mass spectrometry against the expected mass (PubChem lists C69H111N23O16S, about 1551 Da, for apelin-13), purity by reverse-phase HPLC with the trace shown, net peptide content separate from gross weight, counter-ion identity and an endotoxin measurement [12]. The sequence is strongly basic with multiple arginines, so counter-ion content can be a substantial share of gross weight.

How purity testing works · Reading a certificate of analysis

Check a Apelin-13 certificate of analysis against its expected mass (1,550.8 Da)

Storage and handling

General research-context handling only. Lyophilised peptides of this type are generally kept dry, cool and protected from light and moisture, and aqueous solutions of a rapidly cleared, protease-sensitive peptide are treated as short-lived. Defer to supplier documentation for the specific lot. No temperatures or preparation steps are given here.

Frequently asked questions

What is apelin-13?

It is a 13-residue C-terminal fragment of the endogenous peptide apelin, which was identified in 1998 as the ligand of the APJ receptor; the pyroglutamyl form (Pyr1)apelin-13 is the version used in human studies ^1,6.

Has it been given to people?

Yes, in short mechanistic studies. Randomized, placebo-controlled infusion studies in heart failure patients and healthy volunteers measured vascular and cardiac responses ^1, and a crossover clamp study in 16 overweight men measured insulin sensitivity ^2. No clinical outcome trial was located.

What happened to blood pressure and cardiac output in those studies?

Systemic infusion increased cardiac index and lowered mean arterial pressure and peripheral vascular resistance in both patients and controls, with heart rate rising only in controls ^1.

Does it affect insulin sensitivity?

In 16 healthy overweight men, the higher of two levels tested significantly improved insulin sensitivity during a hyperinsulinaemic-euglycaemic clamp, which the authors described as the first such demonstration in people; the lower level showed a borderline change ^2.

Is the preclinical evidence consistent?

No. Rodent models report protection in neonatal brain injury, doxorubicin cardiac injury, renal ischaemia-reperfusion and sarcopenia ^4,5,8,9, while a 2026 study reported apelin-13 promoting vascular smooth muscle proliferation and atherosclerosis, and two earlier foam-cell papers have been retracted ^10,11.

Why is it not a medicine?

No application record exists at FDA ^13, and rapid plasma clearance is described as the main practical obstacle, which is why biased agonists and delivery systems such as microneedle patches are being developed instead ^5,7.

Is apelin-13 the same as Pyr-apelin-13?

Not exactly. The pyroglutamyl form carries an N-terminal pyroglutamate and is the circulating species used in the human studies; material should state which form it is ^1,2.

Is it banned in sport?

It is not named individually in the sources reviewed; S0 covers substances with no current governmental approval for human therapeutic use, prohibited at all times, so athletes should ask their anti-doping organisation ^15.

Latest indexed research

Retraction notice to "Corrigendum to "Apelin-13 impedes foam cells formation by activating ClassIIIPI3K/Beclin mediated autophagic pathway"" [Biochem. Biophys. Res. Commun. 575, (2021), 99-100].
Other · Biochemical and biophysical research communications · 2026-10-29
Retraction notice to "Apelin-13 impedes foam cell formation by activating Class III PI3K/Beclin-1-mediated autophagic pathway" [Biochem. Biophys. Res. Commun. 466, (2015), 637-643].
Other · Biochemical and biophysical research communications · 2026-10-29
Apelin-13 exerts neuroprotection through activation of APJ/mTORC2 axis in microglia after Intracerebral Hemorrhage in mice.
Other · Brain research bulletin · 2026-10-23
Apelin-13 Pretreatment Attenuates Age-Associated Renal Fibrotic Remodeling Following I/R Injury.
Other · Biomedicines · 2026-09-10
Apelin-13 prevents GATA4-mediated neuronal senescence by restoring autophagy through mTORC1 inhibition.
Other · humans · Cell death & disease · 2026-07-27

Search all studies on Apelin-13 (PubMed, Europe PMC, ClinicalTrials.gov)

Listed by publication type from the index record. Inclusion is not an endorsement; open the source to read the findings.

Revision history

Meaningful changes to this entry, with dates and sources. Last reviewed Oct 24, 2026. Typo and layout fixes are not listed.

New section· entryOct 24, 2026
New research reference added: Apelin-13.

References

Acute cardiovascular effects of apelin in humans: potential role in patients with chronic heart failure Circulation. 2010
Apelin administration improves insulin sensitivity in overweight men during hyperinsulinaemic-euglycaemic clamp Diabetes Obes Metab. 2018
Effect of Apelin on Insulin Sensitivity in Type 2 Diabetic Volunteers (APELINS-2, NCT02724566) ClinicalTrials.gov. 2026
Apelin-13 ameliorates hypoxic-ischemic brain damage and improves neurological function in neonatal rats by attenuating neuroinflammation via AMPK activation Int Immunopharmacol. 2026
Microneedle patch-based delivery of Pyr-Apelin-13 reverses functional and structural deficits in age-related sarcopenia Sci Rep. 2026
Isolation and characterization of a novel endogenous peptide ligand for the human APJ receptor Biochem Biophys Res Commun. 1998
Design, characterization, and first-in-human study of the vascular actions of a novel biased apelin receptor agonist Hypertension. 2015
Apelin-13 attenuates doxorubicin-induced myocardial injury via the PI3K/AKT and ERK/MAPK signaling pathways Cardiovasc Diagn Ther. 2026
Apelin-13 Pretreatment Attenuates Age-Associated Renal Fibrotic Remodeling Following I/R Injury Biomedicines. 2026
Apelin-13 drives VSMC proliferation and atherosclerosis through REEP5-dependent disruption of ER-mitochondria coupling and glycolytic shift Life Sci. 2026
Retraction notice to "Apelin-13 impedes foam cell formation by activating Class III PI3K/Beclin-1-mediated autophagic pathway" Biochem Biophys Res Commun. 2026
Apelin-13 (CID 25078060) PubChem. 2026
Drugs@FDA application data queried through openFDA for apelin (no matching application record returned on 24 October 2026) openFDA / Drugs@FDA. 2026
Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act (updated May 14, 2026); no entry for apelin in any of the three categories FDA. 2026
International Standard: Prohibited List 2026 World Anti-Doping Agency. 2026

Last reviewed October 24, 2026 by the Amiravo editorial team.

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Specifications

Molecular formula: C₆₉H₁₁₁N₂₃O₁₆S
Molecular weight: 1,550.8 g/mol
CAS number: 217082-58-1
PubChem CID: 25078060
ChEMBL: CHEMBL414173
Sequence: Gln-Arg-Pro-Arg-Leu-Ser-His-Lys-Gly-Pro-Met-Pro-Phe (QRPRLSHKGPMPF); the (Pyr1) form carries an N-terminal pyroglutamate in place of the N-terminal glutamine
Type: Single compound

Identifiers from PubChem. Verify against the supplier’s documentation for your lot.

Research stats

How much has been published, not how good it is.

PubMed records: 653
Indexed as human research: 231
Animal-only research: 307
Randomized controlled trials: 6
Registered trials: 7
Trials with posted results: 0
NIH-funded projects naming it: 10

PubMed records per year (current year is partial).

Counts from title/abstract searches of PubMed, ClinicalTrials.gov, openFDA and NIH RePORTER, checked 2026-10-24. Names shared with other substances can inflate counts. FAERS reports are spontaneous and do not establish cause. Funding shows interest, not evidence. Method

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