ECE2024 Poster Presentations Pituitary and Neuroendocrinology (120 abstracts)
Improvements in diabetes and hypertension were sustained over long-term osilodrostat treatment in patients with Cushing’s disease: A pooled analysis of LINC 3 and LINC 4
Rosario Pivonello 1 , Maria Fleseriu 2 , John Newell-Price 3 , Monica Gadelha 4 , Richard Auchus 5 , Richard Feelders 6 , Andre Lacroix 7 , Shimatsu Akira 8 , Przemysław Witek 9 , Marie Bex 10 , Andrea Piacentini 11 , Alberto Pedroncelli 12,13 & Beverly M.K. Biller 14
1Università Federico II di Napoli, Dipartimento di Medicina Clinica e Chirurgia, Sezione di Endocrinologia, Naples, Italy; 2Oregon Health & Science University, Pituitary Center, Departments of Medicine and Neurological Surgery, Portland, OR, United States; 3University of Sheffield, School of Medicine and Population Health, Sheffield, United Kingdom; 4Medical School and Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Neuroendocrinology Research Center, Endocrinology Section, Rio de Janeiro, Brazil; 5University of Michigan, Department of Pharmacology and Division of Metabolism, Endocrinology and Diabetes, Ann Arbor, MI, United States; 6Erasmus Medical Center, Department of Internal Medicine, Endocrine Section, Rotterdam, Netherlands; 7Centre hospitalier de l’Université de Montréal, Montreal, Canada; 8Omi Medical Center, Kusatsu, Japan; 9Medical University of Warsaw, Department of Internal Medicine, Endocrinology and Diabetes, Warsaw, Poland; 10University Hospitals Leuven, Department of Endocrinology, Leuven, Belgium; 11Recordati SpA, Milan, Italy; 12Recordati AG, Basel, Switzerland; 13Camurus AB, Lund, Sweden; 14Massachusetts General Hospital, Neuroendocrine and Pituitary Tumor Clinical Center, Boston, MA, United States
Introduction: Diabetes mellitus (DM) and hypertension are common comorbidities that pose significant clinical burden in Cushing’s syndrome patients and may be improved by normalising cortisol. In two Phase III trials (LINC3 [NCT02180217]; LINC4 [NCT02697734]), osilodrostat, a potent oral 11β-hydroxylase inhibitor, provided reductions in cortisol and improved clinical manifestations of hypercortisolism in most Cushing’s disease (CD) patients. Here, we describe changes in glycaemic parameters and blood pressure (BP) in a pooled patient population, according to baseline hypertensive and diabetic status.
Methods: LINC3 comprised a 48-week (W) core phase, including an 8W randomised-withdrawal phase for eligible patients. LINC4 included an initial 12W, double-blind, randomised, placebo-controlled period, then 36W of open-label osilodrostat. Both studies included an optional extension. Baseline DM was defined as prior diagnosis, taking antidiabetic medication, HbA1c ≥6.5%, and/or fasting plasma glucose (FPG) ≥126 mg/dl. Baseline hypertension was defined as prior diagnosis, taking antihypertensive medication, and/or systolic/diastolic BP (SBP/DBP) >130/>90mmHg. Data were pooled in a secondary exploratory analysis for all patients with data at baseline and W72; periods whereby patients received placebo are excluded. No formal statistical testing was performed; all analyses are descriptive.
Results: Of patients with baseline DM (n=84/210; 40.0%), mean (SD) FPG and HbA1c, respectively, decreased from 90.9 (17.3) mg/dl and 5.8 (0.8)% at baseline to 87.1 (9.9) mg/dl and 5.4 (0.6)% at W72 for those not receiving antidiabetic treatment during the study, and decreased from 118.1 (33.5) mg/dl and 6.9 (1.0)% at baseline to 102.7 (27.6) mg/dl and 6.1 (0.8)% at W72 in those receiving antidiabetic medication. Higher baseline FPG and HbA1c was associated with greater improvements at W72, demonstrated by a negative correlation between change in FPG and HbA1c from baseline to W72 and baseline FPG and HbA1c (r=−0.60 and −0.68, respectively; P<0.0001). Most patients (n=174/210; 82.9%) had baseline hypertension. ~50% of patients with baseline SBP >130mmHg had SBP ≤130mmHg at W72, and ~60% with baseline DBP >90mmHg had DBP ≤90mmHg at W72. Higher baseline SBP/DBP was associated with greater improvements at W72, demonstrated by a negative correlation between change in SBP/DBP from baseline to W72 and baseline SBP/DBP (r=−0.69/−0.64; P<0.0001).
Conclusion: DM severity and prevalence of hypertension reduced over long-term osilodrostat treatment. Patients with higher baseline FPG, HbA1c, SBP and DBP experienced the greatest reductions in these parameters at W72. These findings highlight the importance of treating hypercortisolism to improve comorbidities in CD patients.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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