The emerging landscape of performance-enhancing peptides modulating GH-IGF1 axis: bridging the gap between clinical evidence and patient self-administration.

Narrative review

“This article was conducted as a narrative review because the available evidence on GH–IGF-1-axis PEPs is highly heterogeneous with respect to compounds, populations, endpoints, and study design, and because a quantitative synthesis would have been inappropriate for most agents included in the review.”

Peptide-based agents targeting the growth hormone–insulin-like growth factor-1 (GH–IGF-1) axis used off-label for physique and performance purposes

“In this review, we use the term performance-enhancing peptides (PEPs) to describe peptide-based agents used off-label for physique and performance purposes, targeting the growth hormone–insulin-like growth factor-1 (GH–IGF-1) axis.”

The evidence base for these peptides is highly uneven, ranging from randomized controlled trials for tesamorelin to a complete absence of peer-reviewed human studies for compounds like CJC-1295 without DAC, PEG-MGF, and IGF-1 LR3.

“At one end of the spectrum, tesamorelin (tier A) is supported by randomized controlled trials within an FDA-approved clinical indication. At the opposite end, CJC-1295 without DAC, PEG-MGF, and IGF-1 LR3 (tier D) have no peer-reviewed human studies and are supported only by preclinical extrapolation and grey-literature user narratives.”

Reported adverse effects include endocrine and metabolic disturbances, fluid retention syndromes, musculoskeletal symptoms, and injection-site reactions.

“Reported adverse effects span endocrine and metabolic disturbances (including prolactin and cortisol elevations, appetite changes, and dysglycaemia), fluid retention syndromes, musculoskeletal symptoms (myalgia/arthralgia), and injection-site reactions.”