Angiotensin II

Written by The Peptide Record editorialClinical review not yet completedLast reviewed 12 September 2026

Angiotensin II (Giapreza) is a real, FDA-approved peptide drug for septic and other vasodilatory shock — genuinely novel in that it's the exact endogenous human peptide itself, not an analog, and it's approved on a hemodynamic surrogate endpoint rather than a proven mortality benefit.

In brief

Should you care? Only relevant if you or someone you know is in intensive care for septic or vasodilatory shock — this is a hospital-only drug with no wellness or grey-market angle at all.

The short version

The exact native peptide — synthetic human angiotensin II, chemically identical to what your body already makes, not an analog.
ATHOS-3 trial: met its hemodynamic endpoint clearly (69.9% vs. 23.4% blood-pressure response) but the mortality difference was not statistically significant (46% vs. 54%, p=0.12).
Real thrombosis risk — 13% vs. 5% for placebo — requiring blood-clot prevention alongside treatment.

What makes it novel

Angiotensin II is a synthetic 8-amino-acid peptide, chemically identical to the endogenous human hormone of the same name — not a modified analog, which is unusual for an approved peptide drug. It works as a direct vasoconstrictor via the angiotensin II type 1 (AT1) receptor, essentially activating the renin-angiotensin-aldosterone system pharmacologically to raise blood pressure in patients whose blood vessels have become dangerously dilated despite standard vasopressor treatment.

The ATHOS-3 trial, and what it did and didn't show

The FDA approved angiotensin II (as Giapreza) on 21 December 2017 based on the ATHOS-3 trial (Khanna et al., N Engl J Med 2017, PMID 28528561): 321 adults with catecholamine-refractory vasodilatory shock (91% septic shock), randomized to angiotensin II or placebo added to standard vasopressors. The primary endpoint — a meaningful blood-pressure response at 3 hours — was clearly met: 69.9% of the angiotensin II group responded versus 23.4% on placebo (p<0.001). The honest caveat: 28-day mortality, a secondary endpoint, was numerically lower with angiotensin II (46% vs. 54%) but the difference was not statistically significant (p=0.12). This is an approval built on a hemodynamic surrogate endpoint, not a proven survival benefit — a later post-hoc subgroup analysis (not part of the original approval) suggested a possible mortality benefit specifically in patients with severe acute kidney injury, but that finding is exploratory and hasn't been independently confirmed.

Safety

The clearest safety signal from ATHOS-3 was a higher rate of thrombotic and thromboembolic events with angiotensin II than placebo (13% vs. 5%), largely deep vein thrombosis — the label recommends concurrent blood-clot prevention unless contraindicated. We could not confirm whether Giapreza carries a boxed (black-box) warning specifically versus only a Warnings and Precautions section on this point; check the current label directly if that distinction matters to you.

Current status

Still marketed, now by Innoviva (which acquired original developer La Jolla Pharmaceutical Company in 2022). This is a hospital/ICU-only IV infusion with no oral, injectable-at-home, or grey-market form, and no relevance to the wellness or grey-market peptide market this site otherwise covers extensively.

References

Khanna A, English SW, Wang XS, et al. (ATHOS-3 Investigators), "Angiotensin II for the Treatment of Vasodilatory Shock," N Engl J Med 2017;377(5):419-430, PMID 28528561, DOI: 10.1056/NEJMoa1704154.
FDA approval history for Giapreza (angiotensin II), initial approval 21 December 2017.