SUN-032 - Safety and Efficacy of Oral Paltusotine in Patients with Acromegaly with or without Prior Somatostatin Receptor Ligand Maintenance: A GRADE-Assessed Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background: Acromegaly is a chronic disorder caused by excess growth hormone secretion from pituitary adenomas. Paltusotine, a selective somatostatin receptor-2 agonist, is an oral therapy for acromegaly. This study systematically evaluates its efficacy and safety versus placebo in patients with or without prior somatostatin receptor ligand maintenance, using GRADE-appraised randomized controlled trial evidence.

Methods and Materials: Embase, PubMed, Cochrane, and ClinicalTrials.gov were searched through December 2025. Six randomized controlled trials assessing the effects of paltusotine in acromegaly were included. Pooled analyses of change in IGF-1, Acromegaly Score Diary (ASD), and Growth Hormone (GH) with adverse effects including hyperglycemia, hypertriglyceridemia, arthralgia, and upper respiratory tract infections were performed using random-effects models in R 4.5.2 using the “metafor” package. Heterogeneity was quantified using I² statistics.

Results: In pooled analyses of randomized controlled trials, oral paltusotine demonstrated significant biochemical and clinical efficacy compared to placebo in patients with acromegaly. Paltusotine was associated with a greater reduction in insulin-like growth factor-1 (IGF-1) levels (mean difference [MD] −0.84; 95% CI −1.14 to −0.54), with low-to-moderate heterogeneity (I² = 38%), significant improvement in acromegaly symptom burden, as measured by acromegaly symptom diary score (MD −5.38; 95% CI −6.01 to −4.75), with no heterogeneity observed (I² = 0%), and a moderate but statistically significant reduction compared to control (standardized mean difference -0.64; 95% CI -1.14 to -0.14).
With regard to safety outcomes, the risk of hyperglycemia did not differ significantly between paltusotine and placebo (risk ratio [RR] 0.95; 95% CI 0.25–3.65), a significantly lower risk of arthralgia compared with placebo (RR 0.51; 95% CI 0.34–0.76), and the incidence of hypertriglyceridemia was numerically higher in the paltusotine group but did not reach statistical significance (RR 3.41; 95% CI 0.58–19.91). Similarly, no significant difference in the risk of upper respiratory tract infection was observed between treatment groups (RR 0.77; 95% CI 0.27–2.18). Overall, heterogeneity in safety outcomes was low (I² ≈ 0%), and no major safety signals were identified.

Conclusion: With a favorable, consistent safety profile compared with placebo, oral paltusotine demonstrates significant efficacy in improving biochemical control and symptom burden in patients with acromegaly. These findings support paltusotine as an effective oral therapeutic option for patients with acromegaly, including those with or without prior maintenance on somatostatin receptor ligands, although further large-scale trials are needed to confirm its long-term safety and durability of response.

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