Peptides for Weight Loss
Overview
6 research peptides are currently studied for weight loss. This guide ranks them by evidence strength and covers their mechanisms, safety profiles, and current clinical status.
GLP-1 — Endogenous hormone with multiple approved analogs
Evidence Rating: A Category: Metabolic / Weight Loss
GLP-1 (Glucagon-Like Peptide-1) is a 30-amino acid incretin hormone secreted by intestinal L-cells in response to food intake. It is the endogenous peptide behind the revolutionary class of GLP-1 receptor agonist drugs including semaglutide (Ozempic/Wegovy), tirzepatide (Mounjaro/Zepbound), and lira...
Key claims: Glucose-dependent insulin secretion; Significant weight loss via receptor agonists.
Peptide YY (PYY) — Human Infusion Studies / Well-Characterized Physiology
Evidence Rating: B Category: Satiety / Metabolic
Peptide YY (PYY) is a 36-amino-acid gut hormone released by L-cells in the ileum and colon following meals. PYY3-36, the predominant circulating form, acts on Y2 receptors in the hypothalamic arcuate nucleus to suppress appetite. It is one of the best-characterized satiety hormones, with human infus...
Key claims: Reduces caloric intake by ~30% in humans; Lower PYY levels in obesity.
Tesofensine — Phase II–III Clinical Trials
Evidence Rating: C Category: Weight Loss / Reuptake Inhibitor
Tesofensine is a triple monoamine reuptake inhibitor (serotonin, norepinephrine, dopamine) originally developed for Alzheimer's and Parkinson's disease. Phase 2 trials demonstrated approximately 10% body weight loss over 24 weeks, making it one of the most effective weight loss agents studied to dat...
Key claims: Produces significant weight loss (~10% body weight); Suppresses appetite and reduces caloric intake.
Amycretin — Phase I–II Clinical Trials
Evidence Rating: C Category: Weight Loss / GLP-1 Agonist
Amycretin is a first-in-class unimolecular peptide co-agonist developed by Novo Nordisk that simultaneously activates both GLP-1 and amylin receptors from a single molecule. It is being developed primarily as an oral tablet for obesity treatment. In the Phase 2 REDEFINE 1 trial, oral amycretin produ...
Key claims: Produces significant weight loss via oral tablet; Dual GLP-1/amylin agonism is synergistic.
Neuromedin U — Preclinical
Evidence Rating: D Category: Metabolic / Appetite
Neuromedin U (NMU) is a neuropeptide originally isolated from porcine spinal cord that plays roles in appetite suppression, energy expenditure, stress response, and smooth muscle contraction. It acts through two G-protein-coupled receptors (NMUR1 peripherally and NMUR2 centrally). Preclinical studie...
Key claims: Potent appetite suppression; Increases energy expenditure.
BAM-15 — Preclinical only
Evidence Rating: D Category: Weight Loss / Metabolic
BAM-15 is a mitochondrial protonophore (uncoupler) that dissipates the proton gradient across the inner mitochondrial membrane, converting stored energy into heat rather than ATP. Unlike older uncouplers like DNP (2,4-dinitrophenol), BAM-15 selectively uncouples mitochondria without depolarizing the...
Key claims: Reduces body fat without reducing food intake; Improves insulin sensitivity.
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