OBJECTIVE: In healthy subjects, subcutaneous injections of GLP-2 have been shown to elicit dose-related decrease in the bone resorption marker, carboxy-terminal telopeptide of type I collagen (CTX), and have been proposed for the treatment of osteoporosis. This study investigated the relation between GLP-2 exposure and decreases in CTX in order to determine whether high concentrations or prolonged exposure was the most effective mode of administration. High GLP-2 concentrations resulted from iv bolus injections, whereas a more protracted stimulation was obtained by subcutaneous injections and the addition of an inhibitor of GLP-2 degradation, a DPP-4 inhibitor, sitagliptin. MATERIALS AND METHODS: Eight healthy subjects were given: a) three intravenous injections of GLP-2 of 0.1, 0.4 and 0.8nmol/kg, b) one subcutaneous injection of 1.6mg GLP-2 and c) one subcutaneous injection of 1.6mg GLP-2 preceded by an intake of sitagliptin. Blood was sampled for measurements of GLP-2 and p-CTX after each intervention. RESULTS: The 0.1, 0.4 and 0.8nmol/kg GLP-2 injections dose-dependently elevated plasma GLP-2 concentrations and decreased CTX, but the decrease was similar regardless of dose. Subcutaneous GLP-2 caused a much more prolonged exposure (with a peak concentration corresponding to 0.4nmol/kg IV) and was associated with a stronger and a more prolonged suppression of CTX, but in spite of significantly increasing exposure, the administration of sitagliptin, had no additional effect. CONCLUSION: The high concentrations obtained by iv administration were less effective with respect to CTX suppression than the prolonged exposure (with much lower peak concentrations). GLP-2 agonists for osteoporosis treatment should therefore be long-acting for best efficacy.
OBJECTIVE: In healthy subjects, subcutaneous injections of GLP-2 have been shown to elicit dose-related decrease in the bone resorption marker, carboxy-terminal telopeptide of type I collagen (CTX), and have been proposed for the treatment of osteoporosis. This study investigated the relation between GLP-2 exposure and decreases in CTX in order to determine whether high concentrations or prolonged exposure was the most effective mode of administration. High GLP-2 concentrations resulted from iv bolus injections, whereas a more protracted stimulation was obtained by subcutaneous injections and the addition of an inhibitor of GLP-2 degradation, a DPP-4 inhibitor, sitagliptin. MATERIALS AND METHODS: Eight healthy subjects were given: a) three intravenous injections of GLP-2 of 0.1, 0.4 and 0.8nmol/kg, b) one subcutaneous injection of 1.6mg GLP-2 and c) one subcutaneous injection of 1.6mg GLP-2 preceded by an intake of sitagliptin. Blood was sampled for measurements of GLP-2 and p-CTX after each intervention. RESULTS: The 0.1, 0.4 and 0.8nmol/kg GLP-2 injections dose-dependently elevated plasma GLP-2 concentrations and decreased CTX, but the decrease was similar regardless of dose. Subcutaneous GLP-2 caused a much more prolonged exposure (with a peak concentration corresponding to 0.4nmol/kg IV) and was associated with a stronger and a more prolonged suppression of CTX, but in spite of significantly increasing exposure, the administration of sitagliptin, had no additional effect. CONCLUSION: The high concentrations obtained by iv administration were less effective with respect to CTX suppression than the prolonged exposure (with much lower peak concentrations). GLP-2 agonists for osteoporosis treatment should therefore be long-acting for best efficacy.
Authors: Alessandra Amato; Patrizia Proia; Gaetano Felice Caldara; Angelina Alongi; Vincenzo Ferrantelli; Sara Baldassano Journal: Int J Environ Res Public Health Date: 2021-02-23 Impact factor: 3.390
Authors: Sarina Gadgaard; Wijnand J C van der Velden; Sine P Schiellerup; Jenna Elizabeth Hunt; Maria B N Gabe; Johanne Agerlin Windeløv; Geke Aline Boer; Hannelouise Kissow; Cathrine Ørskov; Jens J Holst; Bolette Hartmann; Mette M Rosenkilde Journal: Br J Pharmacol Date: 2022-01-11 Impact factor: 9.473
Authors: Ryan A Lafferty; Finbarr P M O'Harte; Nigel Irwin; Victor A Gault; Peter R Flatt Journal: Front Endocrinol (Lausanne) Date: 2021-05-18 Impact factor: 5.555