Background: We previously reported the efficacy of a combined treatment of active acromegaly with both long-acting somatostatin analogs (SSA) and pegvisomant (PEG-V).

Objective: To assess long-term efficacy and safety in a larger group of acromegalic patients after a period of 138 (35–149) weeks (median(range)).

Design: Pegvisomant was added to high-dose SSA treatment in 32 subjects (13 females), who had not shown a normalization in serum IGF-I concentrations during SSA monotherapy. PEG-V dosage was increased until IGF-I concentration normalized. The maximal dose was twice weekly 80 mg.

Results: After dose-finding, IGF-I remained within the normal range in all subjects with PEG-V administered once (n = 24) or twice (n = 8) weekly, on a total weekly dose of 60 (40–160) mg. Baseline IGF-I levels were positively correlated with the required dosage of PEG-V (r = 0.48; p = 0.006). PEG-V independent liver enzyme disturbances were observed in 11 (6 diabetic) subjects, in which symptomatic gallstones explained 2 cases. These liver enzyme disturbances were transient in all subjects without discontinuation or dose adaptation of PEG-V. In our series, diabetic patients had a 5.1 (odds ratio) (CI 1.02–25.54; p<0.05) higher risk for developing liver enzyme disturbances. These liver enzyme disturbances seemed to occur earlier. Pituitary adenoma size decreased in 4 patients. No increase in tumor size was observed in any of the patients.

Conclusion: Long-term combined treatment with long-acting SSA and (twice) weekly PEG-V for active acromegaly seems to be effective and safe. Patients with acromegaly and diabetes seem to have a higher risk in developing transient liver enzyme disturbances.