机构：[1]Baylor College of Medicine, Houston, TX, USA[2]Peking Union Medical College Hospital, Beijing, China[3]Centre for Cancer and Organ Diseases, Rigshospitalet,Copenhagen University, Copenhagen, Denmark[4]Sun Yat‑Sen Memorial Hospital, Sun Yat-Sen University,Guangzhou, China中山大学附属第二医院[5]West China Hospital, Sichuan University, Chengdu, China四川大学华西医院[6]Military Institute of Medicine and Medical Universityof Warsaw, Warsaw, Poland[7]MS Ramaiah Medical College and Hospitals, Bengaluru,India[8]Novartis Pharma AG, Basel, Switzerland[9]Novartis Pharmaceuticals Corporation, East Hanover, NJ,USA[10]Wroclaw Medical University, Wroclaw, Poland[11]Mayo Clinic, 4500 San Pablo Road,Jacksonville, FL 32224, USA[12]Recordati AG, Basel, Switzerland
Purpose Pasireotide is an effective treatment for acromegaly and Cushing's disease, although treatment-emergent hyperglycemia can occur. The objective of this study was to assess incretin-based therapy versus insulin for managing pasireotide-associated hyperglycemia uncontrolled by metformin/other permitted oral antidiabetic drugs. Methods Multicenter, randomized, open-label, Phase IV study comprising a core phase (<= 16-week pre-randomization period followed by 16-week randomized treatment period) and optional extension (ClinicalTrials.gov ID: NCT02060383). Adults with acromegaly (n = 190) or Cushing's disease (n = 59) received long-acting (starting 40 mg IM/28 days) or subcutaneous pasireotide (starting 600 mu g bid), respectively. Patients with increased fasting plasma glucose (>= 126 mg/dL on three consecutive days) during the 16-week pre-randomization period despite metformin/other oral antidiabetic drugs were randomized 1:1 to open-label incretin-based therapy (sitagliptin followed by liraglutide) or insulin for another 16 weeks. The primary objective was to evaluate the difference in mean change in HbA(1c) from randomization to end of core phase between incretin-based therapy and insulin treatment arms. Results Eighty-one (32.5%) patients were randomized to incretin-based therapy (n = 38 received sitagliptin, n = 28 subsequently switched to liraglutide; n = 12 received insulin as rescue therapy) or insulin (n = 43). Adjusted mean change in HbA(1c) between treatment arms was - 0.28% (95% CI - 0.63, 0.08) in favor of incretin-based therapy. The most common AE other than hyperglycemia was diarrhea (incretin-based therapy, 28.9%; insulin, 30.2%). Forty-six (18.5%) patients were managed on metformin (n = 43)/other OAD (n = 3), 103 (41.4%) patients did not require any oral antidiabetic drugs and 19 patients (7.6%) were receiving insulin at baseline and were not randomized. Conclusion Many patients receiving pasireotide do not develop hyperglycemia requiring oral antidiabetic drugs. Metformin is an effective initial treatment, followed by incretin-based therapy if needed. ClinicalTrials.gov ID: NCT02060383.
第一作者机构：[1]Baylor College of Medicine, Houston, TX, USA[11]Mayo Clinic, 4500 San Pablo Road,Jacksonville, FL 32224, USA
通讯作者：
通讯机构：[1]Baylor College of Medicine, Houston, TX, USA[11]Mayo Clinic, 4500 San Pablo Road,Jacksonville, FL 32224, USA
推荐引用方式(GB/T 7714)：
Susan L. Samson,Feng Gu,Ulla Feldt‑Rasmussen,et al.Managing pasireotide-associated hyperglycemia: a randomized, open-label, Phase IV study[J].PITUITARY.2021,24(6):887-903.doi:10.1007/s11102-021-01161-4.
APA：
Susan L. Samson,Feng Gu,Ulla Feldt‑Rasmussen,Shaoling Zhang,Yerong Yu...&Marek Bolanowski.(2021).Managing pasireotide-associated hyperglycemia: a randomized, open-label, Phase IV study.PITUITARY,24,(6)
MLA：
Susan L. Samson,et al."Managing pasireotide-associated hyperglycemia: a randomized, open-label, Phase IV study".PITUITARY 24..6(2021):887-903
