Endocrine Abstracts

JOINT2551

Background: Pasireotide long-acting release (PasiLAR) is a somatostatin multireceptor ligand commonly used as a second-line medical treatment in patients with acromegaly resistant to first-generation somatostatin receptor ligands (fg-SRLs). PasiLAR is more effective in achieving biochemical control and its tolerability is similar to the fg-SRLs, with the exception of a greater incidence and severity of hyperglycemia. A comprehensive assessment of the metabolic effects of PasiLAR in patients with acromegaly has however not been performed to date. This systematic review and meta-analysis aims to synthesize evidence on PasiLAR effects on lipid and glucose metabolism in patients with acromegaly.

Methods: A comprehensive search was conducted in MEDLINE, Embase, Cochrane Library, and Web of Science for studies published between 2000 and 2024 and retrieved 3441 records. Studies assessing lipid and glucose metabolism in patients with acromegaly on treatment with PasiLAR for at least 6 months were included. Two reviewers screened eligible publications, extracted outcomes, and assessed risk of bias. This systematic review followed Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines and was registered in PROSPERO in May 2024 (registration number: CRD42024544686).

Results: We included a total of 19 studies (18 only PasiLAR, 1 PasiLAR plus PegV), involving 896 patients with acromegaly. Nine studies were retrospective (47%) and ten were prospective randomized controlled trials (53%). A majority of patients included in the meta-analysis were male (58%). Median age (IQR) was 45.8 (43.0 to 47.8) years. PasiLAR treatment was associated with a significantly higher levels of high-density lipoprotein cholesterol (HDL-C) (mean difference [MD] 6.2 mg/dl; 95% confidence interval [CI] 1.4-10.9) and no significant changes in triglycerides, total cholesterol, or low-density lipoprotein cholesterol compared to baseline. PasiLAR treatment was associated with increased fasting plasma glucose (FPG) (MD 23.4 mg/dl; 95% CI 18.8-28.1) and glycosylated hemoglobin (HbA1c) (MD 0.5%; 95% CI, 0.4-0.7). Diabetes frequency was higher after treatment (58.6%) compared to baseline (30.9%), with an odds ratio of 3.7 (95% CI 2.9-4.7).

Conclusions: This systematic review and meta-analysis is the first comprehensive evaluation of the effects of PasiLAR treatment on both lipid and glucose metabolism in patients with acromegaly. Treatment with PasiLAR for at least 6 months was associated with increased HDL-C, FPG, HbA1c, and frequency of diabetes mellitus in patients with acromegaly. These findings are novel and emphasize the importance of a personalized approach to the treatment of acromegaly with a careful examination of metabolic status, to prevent impairment of lipid and glucose metabolism.