CONTEXT: First-generation somatostatin receptor ligands (fg-SRLs) represent the mainstay of medical therapy for acromegaly, but they provide biochemical control of disease in only a subset of patients. Various pretreatment biomarkers might affect biochemical response to fg-SRLs. OBJECTIVE: To identify clinical predictors of the biochemical response to fg-SRLs monotherapy defined as biochemical response (insulin-like growth factor (IGF)-1 ≤ 1.3 × ULN (upper limit of normal)), partial response (>20% relative IGF-1 reduction without normalization), and nonresponse (≤20% relative IGF-1 reduction), and IGF-1 reduction. DESIGN: Retrospective multicenter study. SETTING: Eight participating European centers. METHODS: We performed a meta-analysis of participant data from 2 cohorts (Rotterdam and Liège acromegaly survey, 622 out of 3520 patients). Multivariable regression models were used to identify predictors of biochemical response to fg-SRL monotherapy. RESULTS: Lower IGF-1 concentration at baseline (odds ratio (OR) = 0.82, 95% confidence interval (CI) 0.72-0.95 IGF-1 ULN, P = .0073) and lower bodyweight (OR = 0.99, 95% CI 0.98-0.99 kg, P = .038) were associated with biochemical response. Higher IGF-1 concentration at baseline (OR = 1.40, (1.19-1.65) IGF-1 ULN, P ≤ .0001), the presence of type 2 diabetes (oral medication OR = 2.48, (1.43-4.29), P = .0013; insulin therapy OR = 2.65, (1.02-6.70), P = .045), and higher bodyweight (OR = 1.02, (1.01-1.04) kg, P = .0023) were associated with achieving partial response. Younger patients at diagnosis are more likely to achieve nonresponse (OR = 0.96, (0.94-0.99) year, P = .0070). Baseline IGF-1 and growth hormone concentration at diagnosis were associated with absolute IGF-1 reduction (β = 0.90, standard error (SE) = 0.02, P ≤ .0001 and β  = 0.002, SE = 0.001, P = .014, respectively). CONCLUSION: Baseline IGF-1 concentration was the best predictor of biochemical response to fg-SRL, followed by bodyweight, while younger patients were more likely to achieve nonresponse.

3rd Department of Internal Medicine 1st Medical Faculty Charles University Prague Czech Republic

Aix Marseille Université CNRS Marseille France

APHM Hôpital Conception Service d'Endocrinologie Diabète et Maladies Métaboliques Centre de Référence des Maladies Rares d'Origine Hypophysaire Marseille France

Assistance Publique Hôpitaux de Paris Hôpital de Bicêtre Service d'Endocrinologie et des Maladies de la Reproduction Centre de Référence des Maladies Rares de l'Hypophyse Le Kremlin Bicêtre France

Clinical Neuroendocrinology Max Planck Institute of Psychiatry Munich Germany

Department of Biotechnological and Applied Clinical Sciences University of L'Aquila L'Aquila and Neuromed IRCCS Pozzilli Italy

Department of Endocrinology Diabetes and Metabolism Section and Instituto de Investigação e Inovação em Saúde University of Porto Centro Hospitalar S João Porto Portugal

Department of Endocrinology Diabetes and Nutrition University Hospital of Reims Reims France

Department of Medicine Endocrinology section Pituitary Center Rotterdam Erasmus University Medical Center Rotterdam the Netherlands

Dipartimento di Medicina Clinica e Chirurgia Università Federico 2 di Napoli Naples Italy

Endocrinologie Centre Hospitalier Universitaire de Liège Domaine Universitaire du Sart Tilman Liège Belgium

Servicio de Endocrinología Hospital Universitario La Ribera Valencia Spain

Université Paris Saclay Univ Paris Sud Inserm Signalisation Hormonale Physiopathologie Endocrinienne et Métabolique Le Kremlin Bicêtre France

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