ORF28-01 - Safety of Pasireotide Versus First-Generation Somatostatin Analogs: A Comparative Analysis Base on the FAERS

Objective
Somatostatin receptor ligands (SRLs) are the mainstay of treatment for acromegaly. The second-generation SRL pasireotide was approved in China in April 2025, yet its safety profile and systematic comparison with first-generation SRLs (octreotide and lanreotide) in real-world settings remain limited. This study aimed to comprehensively evaluate and compare the adverse reaction profiles of these SRLs using data from the FDA Adverse Event Reporting System (FAERS), providing evidence for clinical risk management.
Methods
Adverse event reports from the first quarter of 2001 to the fourth quarter of 2025 in the FAERS database, in which pasireotide, octreotide, or lanreotide was listed as the primary suspected drug, were extracted. Safety signals were detected using the reporting odds ratio (ROR).
Results
A total of 29,821 reports for octreotide, 9,919 for lanreotide, and 2,483 for pasireotide were included. Pasireotide had the highest rate of serious adverse reaction reports (32.1%), significantly higher than octreotide (21.4%) and lanreotide (18.7%) (p < 0.01). The adverse reaction profiles differed among the three drugs: Octreotide was most commonly associated with diarrhea (ROR = 3.56, 95% CI 3.02–4.20) and fatigue (ROR = 2.95, 95% CI 2.30–3.78);Lanreotide was primarily linked to diarrhea (ROR = 4.12, 95% CI 3.25–5.22) and vitamin B12 deficiency (ROR = 2.78, 95% CI 2.15–3.60); Pasireotide showed strong associations with hyperglycemia (ROR = 8.73, 95% CI 7.15–10.66) and diabetic ketoacidosis (ROR = 6.24, 95% CI 4.82–8.08).
In terms of metabolic safety, the incidence of hyperglycemia-related adverse reactions was 3.1 times higher in the pasireotide group than in the octreotide group (95% CI 2.7–3.6). Among elderly patients (≥65 years), pasireotide increased the risk of hyperglycemia events requiring hospitalization by 5.8-fold. Regarding gastrointestinal effects, the reporting rate of gallstones was higher with octreotide (11.2%) than with lanreotide (7.4%, p < 0.001). It should be noted that FAERS data have inherent limitations, including reporting bias, incomplete information, and population representativeness bias.
Conclusion
This study is systematically reveal differences in safety profiles between pasireotide,octreotide and lanreotide using FAERS data. First-generation SRLs warrant attention for gallstones (octreotide) or injection-site reactions and vitamin B12 deficiency (lanreotide). In contrast, pasireotide carries a significant risk of hyperglycemia and related metabolic disorders. These findings highlight the need for individualized monitoring based on the specific risk profiles of each SRL, such as enhanced blood glucose management and cardiovascular evaluation when using pasireotide, to optimize treatment safety. Further real-world studies are needed to validate the safety characteristics of Pasireotide