Efficacy and safety of pharmacologic therapies in acromegaly: a systematic literature review and network meta-analysis
Clinical Snapshot
PICO Framework
| P — Population | Adults with acromegaly requiring pharmacological treatment |
| I — Intervention | Various pharmacological treatments including somatostatin receptor ligands (lanreotide autogel, octreotide LAR, pasireotide, oral octreotide, subcutaneous octreotide depot), GH receptor antagonist (pegvisomant), and oral SRL (paltusotine) |
| C — Comparator | Head-to-head comparisons between different acromegaly pharmacotherapies via network meta-analysis |
| O — Outcomes | Biochemical control rates, treatment discontinuation due to adverse events, treatment-emergent adverse events, serious adverse events |
Bottom Line
This network meta-analysis of 18 randomized controlled trials provides valuable indirect comparisons of acromegaly pharmacotherapies. While most established treatments showed comparable biochemical control rates, paltusotine emerged as a promising oral alternative to injectable somatostatin receptor ligands, demonstrating superior efficacy compared to oral and subcutaneous octreotide formulations with lower discontinuation rates due to adverse events. The study's strength lies in its rigorous Bayesian methodology and comprehensive outcome assessment. However, the evidence requires cautious interpretation given industry involvement in authorship and the need for real-world clinical validation. For Australian clinicians, these findings may inform treatment discussions, particularly for patients seeking oral alternatives to injectable therapies, though PBS accessibility and cost-effectiveness considerations will influence practical implementation. The results support paltusotine as a potential first-line oral option pending regulatory approval and clinical experience confirmation.
Key Findings
P Value: Not explicitly reported - Bayesian analysis uses credible intervals
Effect Size: Paltusotine vs O-OCT: OR 7.34; Paltusotine vs SC-OCT-D: OR 7.85; Pasireotide vs OCT-LAR: OR 2.03
Primary Outcome: Biochemical control rates were comparable among most treatments, with paltusotine showing superior efficacy compared to oral and subcutaneous octreotide formulations
Nnt Or Sensitivity: Paltusotine ranked highest probability for most effective treatment across all endpoints studied
Confidence Interval: 95% credible intervals: [1.48-36.07], [1.72-36.25], and [1.29-3.23] respectively
Clinical Application
High feasibility for specialist endocrinology practice, though paltusotine availability and cost considerations may limit accessibility Relevant to Australian endocrinology practice; PBS listing status for newer agents like paltusotine would influence clinical adoption; aligns with RACGP referral guidelines for specialist acromegaly management Adults with acromegaly requiring pharmacological treatment, particularly those considering alternatives to injectable somatostatin receptor ligands
Abstract
CONTEXT: There are limited head-to-head trials comparing pharmacological treatments for acromegaly. OBJECTIVE: Systematically review the efficacy and safety of pharmacological treatments for acromegaly and conduct a network meta-analysis (NMA) enabling indirect comparisons. METHODS: MEDLINE and Embase were searched to identify randomized controlled trials (RCTs) of acromegaly therapies. Screening and data extraction followed PRISMA guidelines. Feasibility assessment evaluated homogeneity and consistency assumptions required for NMA. Bayesian NMAs estimated relative treatment effects and ranking probabilities. RESULTS: Twenty-two records covering 18 RCTs were included. Biochemical control rates were comparable among long-acting injectable somatostatin receptor ligands (SRLs), including lanreotide autogel (LAN-ATG), octreotide long-acting release (OCT-LAR), pasireotide, the GH receptor antagonist pegvisomant, oral octreotide (O-OCT), octreotide subcutaneous depot (SC-OCT-D), and the once-daily oral SRL paltusotine. Paltusotine demonstrated significantly higher biochemical control vs O-OCT and SC-OCT-D (odds ratios [ORs], 95% credible intervals [CrIs]: 7.34 [1.48-36.07] and 7.85 [1.72, 36.25]). Pasireotide showed significantly higher biochemical control vs OCT-LAR (OR: 2.03 [1.29-3.23]). Paltusotine had significantly lower discontinuations due to adverse events (AEs) vs O-OCT and SC-OCT-D, (ORs: 0.022 [0.001-0.424] and 0.022 [0.001-0.343]), with similar rates to other treatments. Treatment-emergent AEs (TEAEs) and serious TEAEs were comparable across treatments. Rankings suggested paltusotine as the treatment with the highest probability of ranking as the most effective (or tolerable) treatment across all endpoints studied. CONCLUSION: This systematic review and NMA consolidate recent high-quality RCT evidence for acromegaly treatments. Paltusotine emerges as a promising alternative to injectable SRLs, with favorable efficacy, safety, and AE-related discontinuation patterns. These findings may inform clinical decision-making and guideline development, if confirmed by clinical experience.
References
- 1.Salvatori, R., Colzani, R. M., Hummel, N., Kopiec, A., Maliszewska, Z., Wang, S., Okeyo, J. C., Cuddihy, R. M., & Nachtigall, L. B. (2026). Efficacy and safety of pharmacologic therapies in acromegaly: a systematic literature review and network meta-analysis. The Journal of Clinical Endocrinology and Metabolism. https://doi.org/10.1210/clinem/dgag085
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