ENEA 2022 | 20th Congress of the European NeuroEndocrine Association - September 7-10, 2022

Impaired insulin secretion without changes in insulin sensitivity explains hyperglycemia in patients with acromegaly treated by pasireotide LAR

P. Wolf*^a (Dr), A. Dormoy^b (Dr), L. Maione^b (Dr), S. Salenave^b (Dr), J. Young^b (Prof), P. Kamenicky^b (Prof), P. Chanson^b (Prof)

^a Medical University of Vienna, Vienna, AUSTRIA ; ^b Hoptial Bicetre, Service d’Endocrinologie et des Maladies de la Reproduction, Le Kremlin-Bicetre, FRANCE

* peter.wolf@meduniwien.ac.at

Background: Pasireotide is a second line treatment for acromegaly. Besides the growth hormone (GH) lowering efficacy, clinical use is limited by side effects on glycemic control. The aim of this study was to evaluate longitudinal changes in beta-cell function and insulin sensitivity induced by pasireotide therapy in patients with acromegaly.

Methods: We performed a retrospective study in 33 patients. Efficacy (GH and IGF-I concentrations; tumor size) and effects on glycemic control were analyzed in all patients. In 14 patients longitudinal data on oral glucose tolerance tests were available before, shortly (mean±SD: 6.1±3.8 months) and on long term (mean±SD: 24.4±11.1 months) after initiation of pasireotide therapy. Insulin secretion (Insulinogenic index; Disposition index) and insulin sensitivity were calculated by validated indices.

Results: Hyperglycemia induced by pasireotide was mediated by impaired insulin secretion, which occurred shortly after initiation of treatment and then remained stable on long term (median (min; max): Insulinogenic index: 80 (12; 542) vs 16 (6.4; 101) vs 25 (3.7; 396) pmol/mmol, respectively; p=0.028; Disposition index 1.45 (0.42; 4.88) vs 0.53 0.17; 2.63) vs 0.60 (0.22; 1.71), respectively; p=0.024). No significant changes in insulin sensitivity were observed, despite a marked reduction of GH/IGF-I concentrations. Older age and a worse glycemic control at baseline were the strongest predictors for hyperglycemia and the need for an antidiabetic treatment.

Discussion: Worsening of glycemic control during pasireotide therapy is caused by an impaired insulin secretion, whereas insulin sensitivity is not affected. These findings might be important for the choice of the anti-diabetic treatment for pasireotide induced hyperglycemia.

The author has declared no conflict of interest.