Risk factors and management of pasireotide-associated hyperglycemia in acromegaly

Mônica Gadelha (1) , Feng Gu (2) , Marcello Bronstein (3) , Thierry Brue (4, 5) , Maria Fleseriu (6) , Ilan Shimon (7) , Aart van Der Lely (8) , Shoba Ravichandran (9) , Albert Kandra (10) , Alberto Pedroncelli (10) , Annamaria Colao (11)

1 HUCFF / UFRJ - Hospital Universitário Clementino Fraga Filho [Rio de Janeiro]
2 PUMCH - Peking Union Medical College Hospital [Beijing]
3 University of Sao Paulo Medical School
4 MMG - Marseille medical genetics - Centre de génétique médicale de Marseille
5 Service d'endocrinologie, diabète, maladies métaboliques [Hôpital de la Conception - APHM]
6 LA CONCEPTION - Hôpital de la Conception [CHU - APHM]
7 OHSU - Oregon Health and Science University [Portland]
8 TAU - Tel Aviv University
9 Erasmus MC - Erasmus University Medical Center [Rotterdam]
10 Novartis Pharmaceuticals Corporation [East Hanover, NJ]
11 Recordati AG

Pasireotide, a multireceptor-targeted somatostatin analog with highest affinity for somatostatin receptor subtype (SST) 5, has demonstrated superior efficacy over the SST 2 -preferential somatostatin analogs octreotide and lanreotide. The safety profile is similar to those of octreotide and lanreotide, except for a higher frequency and degree of hyperglycemia. This analysis investigated baseline characteristics and occurrence and management of hyperglycemia during pasireotide treatment in patients with acromegaly treated in two prospective clinical studies, SOM230C2305 (C2305) and SOM230C2402 (C2402; PAOLA). One hundred and seventy-eight patients naïve to medical therapy at baseline (C2305) and 125 uncontrolled on first-generation somatostatin analogs at baseline (C2402) received long-acting pasireotide in these studies. Of patients treated with pasireotide in studies C2305 and C2402, respectively, 75.3 (134/178) and 65.6% (82/125) developed hyperglycemia or experienced worsening of existing hyperglycemia. Occurrence of hyperglycemia during pasireotide treatment was less frequent in patients with lower age (<40 years, C2402; <30 years, C2305), normal glucose tolerance, and no history of hypertension or dyslipidemia at baseline. Thirteen (4%) patients discontinued pasireotide because of hyperglycemia-related adverse events. Metformin alone or in combination with other oral antidiabetic medications controlled elevations in glucose levels in most pasireotide-treated patients; 78% of C2305 patients and 73 (pasireotide 40 mg) and 60% (pasireotide 60 mg) of C2402 patients achieved the ADA/EASD goal of HbA 1c <7% (<53 mmol/mol) at the end of the core phase. Not all patients develop hyperglycemia, and it is reversible upon pasireotide withdrawal. Close monitoring, patient education and prompt action remain key elements in addressing hyperglycemia during pasireotide treatment.

Mots clés: pasireotide; acromegaly; hyperglycemia; diabetes mellitus

Domaines: Médecine humaine et pathologie

Mônica Gadelha, Feng Gu, Marcello Bronstein, Thierry Brue, Maria Fleseriu, et al.. Risk factors and management of pasireotide-associated hyperglycemia in acromegaly. Endocrine Connections, 2020, 9 (12), pp.1178-1190. ⟨10.1530/EC-20-0361⟩. ⟨hal-03225564⟩