Pharmacodynamic hormonal effects of anamorelin, a novel oral ghrelin mimetic and growth hormone secretagogue in healthy volunteers.
OBJECTIVE
Activation of ghrelin receptors stimulates GH secretion and appetite, increasing lean body mass and body weight. However, clinical use of ghrelin is limited because it has a short half-life and must be administered parenterally. Anamorelin is a novel, orally active, non-peptidic ghrelin mimetic and growth hormone secretagogue. Our objective was to evaluate its hormonal effects in healthy subjects.


METHODS
A double-blind, randomized, placebo-controlled study evaluated the short-term effects of anamorelin on GH, insulin-like growth factor-1 (IGF-1), insulin-like growth factor binding protein 3 (IGFBP-3), prolactin, ACTH, LH, FSH, TSH, cortisol, insulin and glucose. Normal healthy volunteers (n=32) recruited from the general population were administered escalating doses of anamorelin (25, 50, and 75 mg daily) vs. placebo.


RESULTS
Anamorelin significantly increased GH levels at all doses (p<or=0.01). Effects on the somatotropic axis were maintained, as evidenced by sustained increases in IGF-1 and IGFBP-3 compared to placebo following 5-6 days of treatment. Negligible effects on other anterior pituitary hormone profiles and on fasting glucose were noted and all mean hormone levels remained within normal range. Some degree of insulin resistance as assessed by HOMA-IR was evident after treatment with 75 mg dose but not with the 25 or the 50 mg doses. Significant dose-related increases in body weight were recorded. Changes in body weight directly correlated with changes in IGF-1 levels. Anamorelin was well tolerated.


CONCLUSIONS
Anamorelin increases GH, IGF-1, IGFBP-3 and body weight with good tolerability and selectivity, without affecting other anterior pituitary axes or fasting glucose levels.
Garcia
José M
JM
Division of Diabetes, Endocrinology and Metabolism, Michael E. DeBakey Veterans Affairs Medical Center, Baylor College of Medicine, Houston, TX 77030, USA. jgarcia1@bcm.tmc.edu
Polvino
William J
WJ
D000284:Administration, Oral; D000293:Adolescent; D000324:Adrenocorticotropic Hormone / Q000187:drug effects / Q000378:metabolism; D000328:Adult; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects*; D004311:Double-Blind Method; D005260:Female; D005640:Follicle Stimulating Hormone / Q000378:metabolism; D054439:Ghrelin / Q000031:analogs & derivatives / Q000494:pharmacology*; D006728:Hormones / Q000378:metabolism*; D019382:Human Growth Hormone / Q000378:metabolism*; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010919:Placebos; D011388:Prolactin / Q000187:drug effects / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000187:drug effects / Q000378:metabolism; D013972:Thyrotropin / Q000187:drug effects / Q000378:metabolism; D055815:Young Adult
D001786:Blood Glucose; D054439:Ghrelin; D006728:Hormones; C515497:IGFBP3 protein, human; D007328:Insulin; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins; D010919:Placebos; D019382:Human Growth Hormone; D000324:Adrenocorticotropic Hormone; D011388:Prolactin; D005640:Follicle Stimulating Hormone; D013972:Thyrotropin; D017526:Receptor, IGF Type 1; D006854:Hydrocortisone