Angiotensin (1-7) vs Teriparatide

Binds Mas receptor (MasR), activating nitric oxide synthase and reducing oxidative stress. Opposes TGF-β and angiotensin II signaling to reduce fibrosis. Enhances insulin sensitivity and provides cardiovascular protection.

Angiotensin-(1-7) [Ang-(1-7)] is an endogenous heptapeptide hormone generated primarily through cleavage of angiotensin II by ACE2, functioning as a counter-regulatory arm of the renin-angiotensin system (RAS) by binding the Mas receptor to promote vasodilation, anti-fibrotic, anti-inflammatory, and cardioprotective effects that oppose the vasoconstrictive actions of angiotensin II. Ang-(1-7) acts through the ACE2/Mas receptor axis to reduce oxidative stress, attenuate NF-kB-mediated inflammation, and suppress TGF-beta fibrosis signaling; the ACE2/Ang-(1-7)/Mas axis has emerged as a key regulatory pathway in cardiovascular and metabolic disease, and gained renewed research attention given ACE2's role as the SARS-CoV-2 entry receptor. A Phase 1-2 randomized clinical trial of Ang-(1-7) infusion in COVID-19 ICU patients reported preliminary safety, tolerability, and dose-response data, providing the primary indexed human pharmacokinetic evidence; broader cardiovascular protective applications are supported by preclinical data but have not been established by completed Phase 3 trials. Ang-(1-7) has no FDA approval and no approved therapeutic indication in any jurisdiction; it is an endogenous peptide under active clinical investigation as a candidate for cardiovascular, metabolic, and inflammatory conditions, with emerging human safety data but an incomplete evidence base for any specific approved clinical use.

Recombinant PTH 1-34; when given intermittently, preferentially activates osteoblasts over osteoclasts; increases bone remodeling and net bone formation; stimulates IGF-1 in bone

Teriparatide (PTH(1-34); Forteo) is a synthetic 34-amino-acid peptide corresponding to the biologically active N-terminal fragment of endogenous parathyroid hormone, developed as the first FDA-approved anabolic bone agent for osteoporosis — a compound that stimulates new bone formation rather than merely inhibiting bone resorption. Teriparatide activates the PTH/PTHrP receptor (PTH1R) on osteoblasts; when administered as intermittent pulsatile subcutaneous injections, it drives net bone formation by stimulating osteoblast activity, increasing bone mineral density, improving trabecular microarchitecture, and reducing fracture risk — a distinct mechanism from antiresorptive agents such as bisphosphonates. A comprehensive systematic review and network meta-analysis published in the Annals of Internal Medicine (2023), integrating multiple randomized controlled trials, established teriparatide among the most effective pharmacological interventions for fracture prevention in osteoporosis, with significant reductions in vertebral and non-vertebral fracture risk versus placebo. Teriparatide (Forteo, Eli Lilly) is FDA-approved and requires a prescription; it is indicated for postmenopausal women, men with osteoporosis, and glucocorticoid-induced osteoporosis at high fracture risk, with a maximum treatment duration of two years due to preclinical osteosarcoma findings; biosimilar teriparatide preparations are available in multiple international markets.