Azelaprag
Azelaprag (BGE-105), oral small-molecule apelin receptor agonist
Written by Aaron CuhaReviewed Sep 2026
Also known as: BGE-105, BGE105
The phase 2 trial of azelaprag with tirzepatide in 204 adults with obesity was terminated. The registry's stated reason is liver transaminitis in some participants receiving azelaprag, and no azelaprag trial has been registered since.
Overview
Azelaprag is BioAge Labs' oral agonist at APJ, the apelin receptor. The scientific case came from a 2018 Nature Medicine paper showing that apelin, a peptide released by contracting muscle, declines with age and that restoring apelin signalling reversed age-related muscle deterioration. Every intervention in that paper was in mice; the human part of it was an observational cohort.
BioAge took an oral APJ agonist into people. A phase 1 pharmacokinetic study in 16 older healthy volunteers completed in February 2024. The phase 2, registered as NCT06515418 and named STRIDES, randomised 204 adults with obesity aged 55 and over to azelaprag once daily or twice daily on top of weekly tirzepatide, against tirzepatide alone, with percentage body weight change as the primary outcome. The premise was that an apelin agonist would preserve muscle while a GLP-1 and GIP agonist drove weight loss.
The trial was terminated. The reason given on the registry record, verbatim, is that dosing of both study drugs was discontinued after observation of liver transaminitis without clinically significant symptoms in some subjects receiving azelaprag. The record shows an actual completion date of 12 February 2025 and notes that all participant visits were completed. No efficacy result has been published.
A 2026 drug metabolism paper adds a mechanistic footnote: in three-dimensional primary human liver spheroids, combined exposure to azelaprag and tirzepatide produced synergistic toxicity, which the authors list among the real-world clinical hepatotoxicity signals their model reproduced.
Mechanism of action
Agonism at APJ (APLNR), a class A G protein-coupled receptor whose endogenous ligands are apelin and elabela. Apelin is released by contracting skeletal muscle, falls with age, and in mice drives mitochondrial biogenesis, autophagy and muscle stem cell function. Native apelin peptides are cleared within minutes, which is why the development effort went into orally available small molecules like this one. Whether APJ agonism preserves lean mass in a human on a GLP-1 drug is the question the terminated trial was built to answer and did not.
Human evidence
Two registered human studies exist, one phase 1 pharmacokinetic study in 16 people and one terminated 204-person phase 2. Neither has published a result, and the phase 2 stopped for a liver signal.
- NCT06141889: phase 1, 16 older healthy volunteers, pharmacokinetics only, completed February 2024, no results posted.
- NCT06515418 (STRIDES): phase 2, 204 adults with obesity aged 55 and over, azelaprag once or twice daily plus weekly tirzepatide versus tirzepatide alone, primary endpoint percent body weight change. TERMINATED.
- The registry-stated reason for termination is liver transaminitis without clinically significant symptoms in some participants receiving azelaprag, with dosing of both study drugs discontinued.
- No lean mass, weight or functional result from that trial has been published or posted.
What this does not tell you: Because the trial was terminated and nothing has been posted, there is no published evidence on whether azelaprag does what it was designed to do. Transaminitis without symptoms is an enzyme finding, not a case series of liver failure, and the registry does not say how many participants were affected or how high the enzymes went. A drug that stops a 204-person phase 2 on a liver signal is a programme-ending event, but the underlying numbers are not public.
Reading the research record
This is the cleanest recent example of why exerkine biology has not produced a drug. The mouse result was strong and mechanistically satisfying. The molecule was oral, the sponsor was well funded, and the trial design was smart: pair it with tirzepatide, where lean mass loss during rapid weight loss is a genuine clinical problem, and measure whether the apelin agonist protects muscle. It got to 204 randomised participants and then stopped on a safety signal in the liver, which is where small molecules most often fail.
One correction worth recording, because the trial is frequently miscited. The phase 2 with tirzepatide is STRIDES, NCT06515418. There is no registered azelaprag trial named BICEP.
Nothing about the apelin axis itself is settled by this. Apelin infusion has real, reproducible haemodynamic effects in people, and the sarcopenia hypothesis has never been tested to a clinical endpoint in a human. What is settled is that this particular oral agonist, at the doses used, alongside tirzepatide, produced enough of a liver signal to stop the study.
The evidence, charted
Fig. 1 · evidence composition
2of 4 citations (50%) are in people
Counted from the citation list on this page. The Human count is the same number shown in the badge at the top. Both understate any literature larger than the sources we cite.
Fig. 2 · evidence over time
Evidence spans 4 distinct years, 2018 to 2026, counted from the citation list on this page.
Fig. 3 · legal status at a glance
US
Not approved
UK
Not approved
AU
Not approved
CA
Not approved
Not approved in any of the four jurisdictions shown. A jurisdiction's classification is a regulatory fact, not a verdict on the science; see Legal status below for the full text and any notes.
Fig. 4 · dose response
No human dose response curve exists
We draw this figure where the data supports it. For this compound in humans it does not, so the panel stays empty rather than borrowing an animal curve and implying it transfers.
Key studies & citations
- Human2025
Efficacy and Safety of Oral Azelaprag Plus Once Weekly Tirzepatide Compared with Tirzepatide Alone in Participants with Obesity Aged 55 Years and Over
Phase 2, 204 participants actual, started 27 June 2024, completed 12 February 2025, status TERMINATED. Primary outcomes were mean percent change in body weight for the once-daily and twice-daily azelaprag arms. The registry's stated reason for stopping, verbatim: dosing of both study drugs was discontinued due to observation of liver transaminitis without clinically significant symptoms in some subjects receiving azelaprag. No efficacy results have been posted.
ClinicalTrials.gov NCT06515418 (STRIDES), BioAge Labs - Human2024
Pharmacokinetics Study of Azelaprag (BGE-105) in Older Adult Healthy Volunteers
Phase 1, 16 older adult healthy volunteers, single and multiple dose pharmacokinetics, started 17 November 2023 and completed 2 February 2024. COMPLETED with no results posted and no publication located.
ClinicalTrials.gov NCT06141889, BioAge Labs - In vitro2026
Mechanistically resolved prediction of compound hepatotoxicity using primary human liver spheroids-Application to recent real-world cases
Three-dimensional primary human liver spheroids reproduced several recent clinical hepatotoxicity signals, explicitly including synergistic toxicity on azelaprag and tirzepatide coexposure. In vitro, and published after the trial stopped, so it explains rather than predicts.
Drug Metabolism and Disposition - Animal2018
The exerkine apelin reverses age-associated sarcopenia
The paper the programme was built on. Apelin production falls with age in humans and rodents and correlates with exercise benefit in older people, which is the observational human half. Every intervention, the knockouts and the restoration of apelin signalling that improved muscle function, was in mice. PubMed's metadata labels this record a phase 3 randomised trial because of the embedded human cohort; it is not an apelin administration trial.
Nature Medicine
Frequently asked questions
Did the azelaprag phase 2 work?
Nobody knows, because it did not finish. The trial was terminated for liver transaminitis and no efficacy result has been posted or published. Treat any claim about its weight or muscle results as unsupported.
Why was the trial stopped?
The ClinicalTrials.gov record states that dosing of both study drugs was discontinued after liver transaminitis without clinically significant symptoms was observed in some participants receiving azelaprag. A 2026 human liver spheroid study separately reported synergistic toxicity when azelaprag and tirzepatide were combined.
Can I buy azelaprag?
It is an unapproved investigational small molecule whose only phase 2 stopped on a liver safety signal. Anything sold under that name is not the trial product under trial supervision, and the one known risk of the compound is one you cannot feel.
Is azelaprag the same as apelin?
No. Apelin is the endogenous peptide ligand of the APJ receptor and is cleared within minutes. Azelaprag is an oral small molecule designed to hit the same receptor for long enough to be a drug.
Does this mean apelin does not preserve muscle?
It means the hypothesis has still never been tested to completion in people. The muscle evidence for the apelin axis is a mouse paper from 2018 with an observational human cohort attached. The one trial built to test it in humans stopped early for an unrelated safety reason.