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IGF-1 LR3 vs IGF-1 DES (1-3) vs HGH (Somatropin) vs Mecasermin (Native rhIGF-1) Feature Type IGF-1 LR3 Synthetic IGF-1 analog IGF-1 DES (1-3) Truncated IGF-1 variant HGH (Somatropin) Recombinant growth hormone Mecasermin (Increlex) Recombinant native human IGF-1 Feature Amino acids IGF-1 LR3 83 IGF-1 DES (1-3) 67 HGH (Somatropin) 191 Mecasermin (Increlex) 70 (identical to endogenous IGF-1) Feature Half-life IGF-1 LR3 20-30 hours IGF-1 DES (1-3) ~20-30 minutes HGH (Somatropin) 2-3 hours Mecasermin (Increlex) ~5.8 hours Feature Receptor potency IGF-1 LR3 ~3x native IGF-1 IGF-1 DES (1-3) ~10x native IGF-1 (locally) HGH (Somatropin) Indirect (drives endogenous IGF-1) Mecasermin (Increlex) 1x (it is native IGF-1) Feature Action IGF-1 LR3 Systemic, long-acting IGF-1 DES (1-3) Localized, rapid HGH (Somatropin) Systemic upstream cascade Mecasermin (Increlex) Systemic, replacement therapy Feature Dosing frequency IGF-1 LR3 Once daily IGF-1 DES (1-3) 2-3x daily HGH (Somatropin) 1-2x daily Mecasermin (Increlex) Twice daily SubQ Feature Common dose context IGF-1 LR3 20-100 mcg/day (research) IGF-1 DES (1-3) 50-150 mcg/day split (research) HGH (Somatropin) 2-8 IU/day (research) Mecasermin (Increlex) 0.04-0.12 mg/kg twice daily (clinical) Feature IGFBP binding IGF-1 LR3 Very low IGF-1 DES (1-3) Very low HGH (Somatropin) N/A (acts upstream) Mecasermin (Increlex) Normal (full IGFBP affinity) Feature FDA status IGF-1 LR3 Not approved IGF-1 DES (1-3) Not approved HGH (Somatropin) FDA-approved (multiple indications) Mecasermin (Increlex) FDA-approved (pediatric severe primary IGFD) Feature WADA status IGF-1 LR3 Prohibited IGF-1 DES (1-3) Prohibited HGH (Somatropin) Prohibited Mecasermin (Increlex) Prohibited Feature Practical note IGF-1 LR3 Long-acting IGF-1 analog with the most accumulated community data IGF-1 DES (1-3) Localized, rapid signaling

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Selective and membrane-permeable small molecule inhibitors of nicotinamide N-methyltransferase reverse high-fat diet-induced obesity in mice