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Semaglutide is a long-acting GLP-1 receptor agonist (half-life ~7 days via albumin binding) approved for type 2 diabetes and obesity. It binds the GLP-1R on pancreatic beta cells, hypothalamic appetite circuits, and other tissues, stimulating insulin secretion, suppressing glucagon, slowing gastric emptying, and reducing appetite. STEP 1 trial (n=1961) demonstrated 14.9% mean weight loss at 68 weeks vs. 2.4% placebo. SUSTAIN-6 and LEADER-type cardiovascular outcomes data show significant MACE reduction. SELECT trial (2023, n=17,604) showed 20% reduction in MACE in obese non-diabetic patients — expanding the cardiovascular indication beyond T2D.

Tirzepatide is the first approved dual incretin receptor agonist — a single molecule that co-activates both the GLP-1 receptor (GLP-1R) and the glucose-dependent insulinotropic polypeptide receptor (GIPR). The dual agonism produces weight loss and glycemic effects that exceed those of GLP-1R agonists alone. SURMOUNT-1 trial (n=2539) demonstrated 20.9% mean weight loss at 72 weeks on the highest dose (15 mg) versus 1.5% placebo — the largest weight loss ever demonstrated for any drug in a Phase III trial. SURPASS-2 showed superior HbA1c reduction compared to semaglutide 1 mg. The GIPR contribution to the superior efficacy remains a mechanistic question — GIPR agonism in adipose tissue appears to enhance fat metabolism beyond what GLP-1R agonism achieves alone.

BPC-157 is a synthetic 15-amino acid pentadecapeptide derived from a cytoprotective protein found in human gastric juice. Over 100 animal studies — primarily from the Zagreb research group led by Predrag Sikiric — demonstrate consistent tissue-protective, angiogenic, and healing effects across GI, tendon, wound, and neurological models. The mechanism involves multiple pathways: FAK-paxillin signaling in tendon fibroblasts, VEGF upregulation for angiogenesis, modulation of the nitric oxide system, and upregulation of GH receptor expression. Despite a completed Phase II IBD clinical trial, peer-reviewed human efficacy data remains absent. No completed human RCTs have been published. FDA has prohibited US compounding of BPC-157, and the regulatory trajectory is unfavorable.

PT-141 (bremelanotide) is a cyclic heptapeptide melanocortin receptor agonist that acts centrally on MC3R and MC4R in the CNS to enhance sexual desire and arousal — mechanistically distinct from PDE5 inhibitors (sildenafil, tadalafil) which act peripherally on vascular smooth muscle. FDA-approved as Vyleesi for HSDD in premenopausal women, based on Phase III trials (RECONNECT) showing improvements in satisfying sexual events and sexual desire scores. The central mechanism — brain-based rather than genital blood flow-based — represents a fundamentally different approach to sexual dysfunction. Main adverse effects are nausea (occurring in ~40% of users) and transient blood pressure elevation.

Sermorelin is a synthetic 29-amino-acid N-terminal fragment of endogenous GHRH (44 AA total) that retains full binding affinity for the GHRH receptor on pituitary somatotrophs. Receptor binding triggers Gs protein coupling → cAMP rise → PKA activation → GH transcription and release. Because sermorelin works upstream through the hypothalamic-pituitary axis, GH release remains subject to somatostatin-mediated negative feedback — the key pharmacological distinction from exogenous rhGH. FDA-approved for pediatric GH deficiency; withdrawn from the branded market in 2008 for commercial reasons, then extensively compounded for adult anti-aging use. That compounded access is under increasing regulatory pressure as of 2025.

Thymosin Alpha-1 (Tα1) is a 28-amino-acid N-terminal fragment of prothymosin alpha, naturally produced by thymic epithelial cells and secreted into the bloodstream, with serum levels declining measurably with age. Its core mechanism operates through TLR2 and TLR9 activation on dendritic cells, driving MyD88-dependent NF-κB signaling, DC maturation, Th1 polarization, and downstream IL-2/IFN-γ production that activates CD8+ T cells and NK cells. A meta-analysis of 7 randomized controlled trials in sepsis (Shrivastava et al. 2022, n=573) found a pooled 28-day mortality OR of 0.50 — one of the more striking effect sizes in critical care immunomodulation. Liu et al. (2021, n=127) demonstrated reduced progression to severe COVID-19 in an RCT. Hepatitis B regulatory approval rests on multiple controlled trials showing HBV DNA suppression and HBeAg seroconversion. Limitations: US access is through 503A compounding; contraindicated in active autoimmune disease; aging-specific applications have thinner controlled evidence.