MON-LB079 A Multicenter, Randomized, Open-Label, Phase IV Study Investigating Management of Pasireotide-Associated Hyperglycemia with Incretin-Based Therapy or Insulin in Patients with Acromegaly or Cushing's Disease (CD)

Background: Pasireotide has proven efficacy in acromegaly and CD, although pasireotide-associated hyperglycemia occurs in some patients (pts). We present results from a Phase IV, randomized, open-label study investigating optimal management of pasireotide-associated hyperglycemia uncontrolled by metformin/other oral antidiabetic therapy (OAD) in acromegaly or CD pts (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. Pts with an increase in fasting plasma glucose (≥126 mg/dL on three consecutive days) in the first 16 weeks that continued despite metformin/other OAD were randomized 1:1 to incretin-based therapy (sitagliptin followed by liraglutide; rescue therapy: insulin) or insulin for a further 16 weeks. Primary objective: assess incretin-based therapy versus insulin for HbA(1c) control at end of randomized period. Secondary objectives: assess sustainability of glycemic control and safety in the incretin and insulin arms. Results: A total of 249 pts (acromegaly, n=190; CD, n=59) were enrolled, 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). In the incretin and insulin arms, respectively, 24 (63%) and 29 (67%) pts had diabetes at baseline (not receiving insulin). Median months (range) of exposure to pasireotide: acromegaly, 5.5 (3.7-8.0); CD, 4.1 (1.9-6.8); duration of exposure was similar between treatment arms. In the incretin arm, rescue therapy (addition of insulin to existing treatment) was given 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 HbA(1c) between treatment arms at end of core study was -0.28% (95% CI -0.63, 0.08) in favor of incretin-based therapy: -0.36% (95% CI -0.74, 0.02) for acromegaly, -0.01% (95% CI -0.96, 0.95) for CD. Mean change in HbA(1c) from baseline to end of core study was -0.12% (95% CI -0.36, 0.13) with incretin-based therapy and 0.26% (95% CI -0.01, 0.53) with insulin. Adverse events (AEs) were reported in 36 (95%) pts on incretin-based therapy and 35 (81%) on insulin, most commonly hyperglycemia (incretin-based therapy, n=11 [29%]; insulin, n=8 [19%]); grade 3/4 AEs were recorded in 14 (37%) and six (14%) pts, and serious AEs occurred in four (11%) and one (2%) pt. Three (8%) pts receiving incretin-based therapy discontinued treatment because of AEs, compared with none on insulin. Conclusion: Many patients (41%) did not require antidiabetic medication while on pasireotide. For pts in whom hyperglycemia occurred, metformin/other OAD was an effective initial treatment choice. For hyperglycemia uncontrolled by metformin/other OAD, incretin-based therapy was an effective treatment option. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. Abstracts presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.