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 pre-treatment biomarkers might affect biochemical response to fg-SRLs.To identify clinical predictors of the biochemical response to fg-SRLs monotherapy defined as biochemical- (IGF-1 ≤1.3 x upper limit of normal; ULN), partial- (>20% relative IGF-1 reduction without normalization) and non-response (≤20% relative IGF-1 reduction), and IGF-1 reduction.Retrospective multicenter study.Eight participating European centers.We performed a meta-analysis of participant data from two cohorts (Rotterdam and Liège acromegaly survey (LAS), 622 out of 3520 patients). Multivariable regression models were used to identify predictors of biochemical response to fg-SRL monotherapy.Lower IGF-1 concentration at baseline (OR=0.82, [0.72-0.95] IGF-1 ULN, p=0.0073) and lower bodyweight (OR=0.99, [0.98-0.99] kg, p=0.038) were associated with biochemical response. Higher IGF-1 concentration at baseline (OR=1.40, [1.19-1.65] IGF-1 ULN, p≤0.0001), the presence of type 2 diabetes (oral medication OR=2.48, [1.43-4.29], p=0.0013; insulin therapy OR=2.65, [1.02-6.70], p=0.045) and higher bodyweight (OR=1.02, [1.01-1.04] kg, p=0.0023) were associated with achieving partial response. Younger patients at diagnosis are more likely to achieve non-response (OR=0.96, [0.94-0.99] year, p=0.0070). Baseline IGF-1 and GH concentration at diagnosis were associated with absolute IGF-1 reduction (ß=0.8982, SE=0.0216, p≤0.0001 and ß= -0.0024, SE= 0.0009, p=0.014, respectively).Baseline IGF-1 concentration was the best predictor of biochemical response to fg-SRL, followed by bodyweight, while younger patients are more likely to achieve non-response.