Apelin-13
Evidence: DCardiovascular / Vascular
Evidence Snapshot
What this grade covers
Applies to exact, unmodified Apelin-13 only. The strongest human interventional evidence located for the 13-residue peptide uses the pyroglutamated form [Pyr1]Apelin-13, which is form-specific and must not be silently treated as unmodified Apelin-13 evidence.
Regulatory Context
This page summarizes research on the peptide and does not imply that the peptide is an FDA-approved drug or approved for a particular indication. Molecule-specific regulatory status requires verification against official regulatory records.
Research Takeaway
Apelin-13 is a 13-residue mature apelin peptide and must be distinguished from Apelin-17, Apelin-36, APELA/Elabela, the APLN precursor, and synthetic APJ/APLNR agonists.
Evidence boundary: Human intervention studies frequently use the pyroglutamated form [Pyr1]Apelin-13; that form must be named explicitly rather than treated as an unrestricted synonym for unmodified Apelin-13.
See all 5 evidence claims →Quick Summary
Apelin-13 is a short endogenous apelin-system peptide studied for cardiovascular and metabolic signaling. The strongest controlled human intervention studies located for the 13-residue form used [Pyr1]Apelin-13, a pyroglutamated molecular form, so those findings must remain form-specific rather than being generalized to every unmodified Apelin-13 preparation.
Mechanism & Research Overview
Apelin-13 is a short endogenous apelin-system peptide studied for cardiovascular and metabolic signaling. The strongest controlled human intervention studies located for the 13-residue form used [Pyr1]Apelin-13, a pyroglutamated molecular form, so those findings must remain form-specific rather than being generalized to every unmodified Apelin-13 preparation.
Evidence Claims
Individual scientific statements drawn from the sources cited below, each shown with the specific evidence boundary that statement does not establish.
Supported
Apelin-13 is a 13-residue mature apelin peptide and must be distinguished from Apelin-17, Apelin-36, APELA/Elabela, the APLN precursor, and synthetic APJ/APLNR agonists.
Does not establish
Evidence boundary: Human intervention studies frequently use the pyroglutamated form [Pyr1]Apelin-13; that form must be named explicitly rather than treated as an unrestricted synonym for unmodified Apelin-13.
Sources: Acute cardiovascular effects of apelin in humans: potential role in patients with chronic heart failure; Development and validation of an LC-MS/MS method for detection and quantification of in vivo derived metabolites of [Pyr1]apelin-13 in humans
Supported
In controlled human infusion studies, [Pyr1]Apelin-13 produced measurable peripheral and systemic cardiovascular effects, including vasodilation, increased cardiac index, and reductions in arterial pressure or vascular resistance.
Does not establish
Evidence boundary: This is evidence for the explicitly named pyroglutamated Apelin-13 form and acute human pharmacology, not proof of therapeutic efficacy or long-term safety for unmodified Apelin-13.
Sources: Acute cardiovascular effects of apelin in humans: potential role in patients with chronic heart failure; Sustained cardiovascular actions of APJ agonism during renin-angiotensin system activation and in patients with heart failure; Cardiovascular and renal effects of apelin in chronic kidney disease: a randomised, double-blind, placebo-controlled, crossover study
Supported
A randomized crossover study in overweight men reported improved insulin sensitivity during experimental administration of [Pyr1]Apelin-13.
Does not establish
Evidence boundary: The result is form-specific, acute metabolic physiology and does not establish Apelin-13 as an approved or established weight-loss or diabetes treatment.
Supported
The current human interventional evidence base identified for Apelin-13 is dominated by [Pyr1]Apelin-13 rather than exact unmodified Apelin-13.
Does not establish
Evidence boundary: This molecular-form distinction is the reason the exact unmodified Apelin-13 page remains Grade D despite a meaningful C-level human evidence body for [Pyr1]Apelin-13.
Sources: Acute cardiovascular effects of apelin in humans: potential role in patients with chronic heart failure; Sustained cardiovascular actions of APJ agonism during renin-angiotensin system activation and in patients with heart failure; Apelin administration improves insulin sensitivity in overweight men during hyperinsulinaemic-euglycaemic clamp; Cardiovascular and renal effects of apelin in chronic kidney disease: a randomised, double-blind, placebo-controlled, crossover study; Development and validation of an LC-MS/MS method for detection and quantification of in vivo derived metabolites of [Pyr1]apelin-13 in humans
Supported
No molecule-specific regulatory conclusion is frozen for unmodified Apelin-13 in Stage 2A.
Does not establish
Evidence boundary: Regulatory status requires a later official subject-specific regulatory source; absence of an approval source in this research set is not itself proof of non-approval.
Safety & Evidence Limitations
Considerations reported in the sources cited on this page — not a complete list of every possible risk, and not medical advice.
Safety Consideration
Acute [Pyr1]Apelin-13 studies demonstrate meaningful hemodynamic activity, including reductions in arterial pressure/vascular resistance and changes in cardiac output; hypotension-related effects are therefore a plausible experimental safety concern.Safety Consideration
Most direct human evidence is form-specific to [Pyr1]Apelin-13 rather than unmodified Apelin-13.Safety Consideration
Long-term safety and chronic therapeutic efficacy for unmodified Apelin-13 are not established by the frozen human source set.
Research Areas Being Studied
Research areas discussed on this page reflect the Cardiovascular / Vascular category and the sources cited below.
Findings Reported in Studies
Educational summary only — reported in cited studies, not a claim of proven benefit.
- Cardiovascular and renal effects of apelin in chronic kidney disease: a randomised, double-blind, placebo-controlled, crossover study (2024):
- Development and validation of an LC-MS/MS method for detection and quantification of in vivo derived metabolites of [Pyr1]apelin-13 in humans (2019):
- Apelin administration improves insulin sensitivity in overweight men during hyperinsulinaemic-euglycaemic clamp (2017):
- Sustained cardiovascular actions of APJ agonism during renin-angiotensin system activation and in patients with heart failure (2013):
- Acute cardiovascular effects of apelin in humans: potential role in patients with chronic heart failure (2010):
Study Tables by Evidence Type
Human Studies & Clinical Data
| Title | Year | Population / Model | Dose / Duration / Finding | Safety Notes | Source |
|---|---|---|---|---|---|
| Cardiovascular and renal effects of apelin in chronic kidney disease: a randomised, double-blind, placebo-controlled, crossover study | 2024 | 12 chronic kidney disease patients and 12 matched healthy participants | Randomized crossover study of pyroglutamated Apelin-13 showed cardiovascular/renal pharmacodynamic effects in CKD and controls. | ||
| Development and validation of an LC-MS/MS method for detection and quantification of in vivo derived metabolites of [Pyr1]apelin-13 in humans | 2019 | Six healthy human volunteers infused with [Pyr1]Apelin-13 | Characterized intact [Pyr1]Apelin-13 and its in-vivo human metabolites; C-terminal cleavage was prominent. | ||
| Apelin administration improves insulin sensitivity in overweight men during hyperinsulinaemic-euglycaemic clamp | 2017 | Overweight men; randomized double-blind placebo-controlled crossover | Two doses of [Pyr1]Apelin-13 were tested during clamp conditions; study reported improved insulin sensitivity. | ||
| Sustained cardiovascular actions of APJ agonism during renin-angiotensin system activation and in patients with heart failure | 2013 | Healthy volunteers and chronic stable heart failure patients | Systemic [Pyr1]Apelin-13 increased cardiac index and reduced mean arterial pressure/peripheral vascular resistance, with preserved vasodilation during RAS activation. | ||
| Acute cardiovascular effects of apelin in humans: potential role in patients with chronic heart failure | 2010 | Healthy volunteers, coronary angiography patients, and chronic heart failure patients | [Pyr1]Apelin-13 caused peripheral vasodilation and increased cardiac index while reducing mean arterial pressure/peripheral vascular resistance; Apelin-36 increased coronary flow and altered LV pressure indices. |
Animal / Cell / Preclinical Data
No Animal / Cell / Preclinical Data Listed Yet
This section will be updated as sources are added.
Regulatory Documents & Official Trial Registries
No Regulatory Documents & Official Trial Registries Listed Yet
This section will be updated as sources are added.
Anecdotal Reported Patterns — Not Medical Advice
Anecdotal Reported Patterns — Not Medical Advice
Reported dosing patterns are included for educational context only. They are self-reported, unverified, not medical advice, and not instructions for human use. Community-submitted patterns are not yet available in this Phase 1 prototype; this section is a placeholder reserved for moderated, aggregated community data.
Lab Markers to Discuss With a Clinician
Educational topics only — not self-monitoring instructions.
FAQ
Disclaimer
Educational information only. This page summarizes published and official research and does not provide medical advice, a recommendation, or instructions for human use.
Educational use only. This content is provided for informational and research-summary purposes only. It is not medical advice, not a treatment recommendation, not a dosing guide, and not a substitute for care from a licensed medical professional. Nothing here is intended to diagnose, treat, cure, prevent, or mitigate disease. Reported dosing patterns, when shown elsewhere on the site, must be labeled either as Study / Trial Dosing or Anecdotal Reported Patterns — Not Medical Advice. Community reports are self-reported, unverified, and not scientific proof.
Community-reported experiences, once enabled, must be displayed only as moderated, anonymized, or aggregated data. They are anecdotal, self-reported, unverified, and should never be presented as proof of safety, efficacy, or expected results.
Content status: Published. Last updated 2026-08-25.
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