Effects on glucose metabolism of high-dose octreotide LAR in patients with acromegaly inadequately controlled by conventional somatostatin analog therapy
Gherardo Mazziotti1, Stefania Bonadonna1, Giovanna Bugari2, Annamaria Colao3, Renato Cozzi4, Salvatore Cannavo'5, Laura De Marinis6, Ettore degli Uberti7, Fausto Bogazzi8, Francesco Minuto9, Marcella Montini10, Ezio Ghigo11 & Andrea Giustina1
The effects of conventional somatostatin analog (SSA) regimens on glucose homeostasis seem to have minor clinical impact in acromegaly. Recently, we performed a trial showing that high dose octreotide LAR significantly reduces IGF1 in acromegalic patients uncontrolled with conventional SSA doses. In this post-hoc analysis, we evaluated the effects of high doses versus high frequency octreotide LAR on glucose homeostasis (HbA1c, FPG, HOMA-R) in patients with acromegaly enrolled in this trial. After approval by ethical committee and informed consent, 26 patients (14 F, 12 M, median age 51 years, range: 2778) with uncontrolled acromegaly were randomly treated with high-dose (11 patients: 60 mg/28 days) or high-frequency (15 patients: 30 mg/21 days) octreotide LAR for 6 months. At study entry, seven patients had diabetes mellitus and eight impaired fasting glucose (IFG). After 6-month treatment, glucose metabolism was impaired in six patients (23.1%), improved in two patients (7.7%) and unchanged in the remaining 18 patients (69.2%). Rate of impairment in glucose homeostasis was similar in high doses versus high frequency octreotide LAR (27.3 vs 20.0%; P=0.44). In all six patients with impaired glucose homeostasis, serum IGF1 and/or GH values remained high during treatment, whereas significant decrease (>20%) in serum IGF-I or GH values was observed in 75% of patients in whom glucose homeostasis did not impair (P=0.03). Impairment of glucose homeostasis occurred in 26.7% of patients with pre-existing diabetes mellitus or IFG and in 18.2% of patients with pre-existing normal glucose metabolism (P=0.35). In conclusion, the increase in octreotide LAR doses or frequency did not produce negative effects on glucose metabolism in the majority of patients. In the minority of patients who experienced impairment of glucose homeostasis, this event occurred more frequently in those with persistently uncontrolled acromegaly and it seems to be not dependent on the pre-existing abnormalities of glucose metabolism.