ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2019) 63 P737 | DOI: 10.1530/endoabs.63.P737

A multicentre, randomized, open-label, Phase IV study investigating management of pasireotide-associated hyperglycaemia with incretin-based therapy or insulin in patients with acromegaly or Cushing's disease (CD)

Marek Bolanowski1, Feng Gu2, Ulla Feldt-Rasmussen3, Shaoling Zhang4, Yerong Yu5, Przemyslaw Witek6, Alberto M Pedroncelli7, Heidi Nauwelaerts7, Nadine Jabbour7, Michaela Paul7 & Susan Samson8

1Wroclaw Medical University, Wroclaw, Poland; 2Peking Union Medical College Hospital, Beijing, China; 3Centre for Cancer and Organ Diseases, Rigshospitalet, Copenhagen, Denmark; 4Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China; 5West China Hospital, Sichuan University, Chengdu, China; 6Military Institute of Medicine, Warsaw, Poland; 7Novartis Pharma AG, Basel, Switzerland; 8Baylor College of Medicine, Houston, Texas, USA.

Background: Pasireotide has proven efficacy in acromegaly and CD, although pasireotide-associated hyperglycaemia occurs in some patients. This Phase IV, randomized, open-label study investigated optimal management of pasireotide-associated hyperglycaemia uncontrolled by metformin/oral antidiabetic therapy (OAD) [NCT02060383].

Methods: Adults with acromegaly or CD were enrolled and treated with long-acting pasireotide 40 mg/28 days or subcutaneous pasireotide 600 μg bid, respectively. Patients with increased fasting plasma glucose (≥126 mg/dl on three consecutive days) in the first 16 weeks that continued despite metformin/OAD were randomized 1:1 to incretin-based therapy (sitagliptin followed by liraglutide; rescue therapy: insulin) or insulin for another 16 weeks. Primary objective: assess incretin-based therapy versus insulin for glycaemic control at end of randomized period. Secondary objectives: assess glycaemic control, sustainability of glycaemic control, and safety in both treatment arms.

Results: 249 patients were enrolled (acromegaly, n=190; CD, n=59), 103 (41%) did not require OAD, 46 (19%) were managed on OAD, 19 (8%) had prior insulin; 81 (33%) were randomized to incretin-based therapy (n=38) or insulin (n=43). Twenty-four (63%) patients receiving incretin-based therapy and 29 (67%) receiving insulin had diabetes at baseline (not receiving insulin). Median (range) months of exposure to pasireotide: acromegaly, 5.5 (3.7–8.0); CD, 4.1 (1.9–6.8); exposure was similar between treatment arms. With incretin-based therapy, rescue therapy (addition of insulin to existing medication) was administered in 12/38 (32%) patients for a median (range) duration of 1.8 (0.5–3.7) months. Estimated difference in adjusted mean change in HbA1c between treatment arms at end of study was –0.28% (95% CI –0.63, 0.08) in favour of incretin-based therapy: acromegaly, –0.36% (95% CI –0.74, 0.02); CD, –0.01% (95% CI –0.96, 0.95). Mean change in HbA1c from baseline to end of study was –0.12% (95% CI –0.36, 0.13) and 0.26% (95% CI –0.01, 0.53) with incretin-based therapy and insulin, respectively. Adverse events (AEs) were reported in 36 (95%) patients receiving incretin-based therapy and 35 (81%) receiving insulin, most commonly hyperglycaemia (incretin-based therapy, n=11 [29%]; insulin, n=8 [19%]); grade 3/4 AEs were recorded in 14 (37%) and six (14%) patients and serious AEs observed in four (11%) and one (2%) patient. Three (8%) patients discontinued treatment because of AEs (all on incretin-based therapy).

Conclusion: Antidiabetic medication is not required in many patients treated with pasireotide. For patients in whom hyperglycaemia occurs, metformin/OAD is an effective first-line treatment. For hyperglycaemia uncontrolled by metformin/OAD, incretin-based therapies are an effective treatment option.