MON-029 - Glycemic and Lipidic Profiles of Patients with Acromegaly Long-Term Treated with Pasireotide LAR after Dose Downtitration

Introduction. Pasireotide LAR (PAS-LAR) has demonstrated higher efficacy in controlling acromegaly; however, it results in glycometabolic deterioration in many patients. This can lead to early discontinuation of PAS-LAR therapy, even in patients with biochemically controlled acromegaly. The purpose of this real-world study is to investigate the effects of PAS-LAR dose downtitration on glucose and lipid metabolism in patients with acromegaly.
Methods. A retrospective, single-center, longitudinal study was conducted on 27 patients with acromegaly on PAS-LAR monotherapy. Data on glucose and lipid metabolism were collected 6 months after dose downtitration and at 6 months of treatment in patients on a stable PAS-LAR dose. PAS-LAR dose reduction was performed in patients with remission of acromegaly symptoms and IGF-I values in the lower-normal age-adjusted reference range, with a concomintant clinically relevant worsening of the glucose and lipidic control, applying ADA 2024 criteria, therapeutic targets recommended by the ESC/EAS guidelines, and/or the necessity for a therapeutic intervention with glucose-lowering or lipid-lowering medications.
Results. The total duration of PAS-LAR therapy was 8.5 (IQR:5.2) in patients that underwent PAS-LAR dose reduction, and 7.8 (IQR:5.8; p=0.266) in the stable dose group. The mean duration of PAS-LAR therapy before dose reduction was 7 years (IQR:5.0). PAS-LAR dose down-titration was conducted in 11 out of 27 patients (40.7%). In this group, glucose profile improved in all patients (100%); lipid profile improved in five patients (45.4%), remained stable in four patients (36.3%) and worsened in two patients (18.1%). As compared to patients who underwent PAS-LAR dose reduction, glucose profile did not improve in patients on treatment with stable dose of PAS-LAR (p < 0.001), worsened in 12 patients (75%) and remained stable in 4 patients (25%); lipid profile improved in a patient (6.2%), remained stable in six patients (37.5%) and worsened in nine patients (56.2%) (p=0.033). After dose downtitration, IGF-I levels showed a slight increase, but remained in the normal range.
Discussion. In acromegaly, the impairment of glucose and lipid metabolism should be carefully managed due to the increased overall mortality risk associated with multiple comorbidities. This study suggests that PAS-LAR dose reduction in patients with acromegaly allows maintenance of biochemical disease control with improved glycemic profiles. Furthermore, we showed for the first time that lipid metabolism also improves with dose downtitration. In selected patients on long-term PAS-LAR therapy with good biochemical disease control, but metabolic deterioration, cautious dose reduction initially should be considered, rather than direct discontinuation of the drug.

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