Current Insights into Pasireotide Therapy for Uncontrolled Acromegaly: Biochemical Response, Tumor Reduction, and Glycemic Safety in a Real-World Latin American Cohort.
Pasireotide treatment for acromegaly showed a 50% normalization rate of IGF-1 and a significant reduction in tumor size, but also increased HbA1c and diabetes incidence.
Where it sits
this study against the rest of the pasireotide corpusSummary and findings
This study evaluated the outcomes of pasireotide treatment in patients with acromegaly inadequately controlled on first-generation somatostatin receptor ligands. The primary endpoint was IGF-1 normalization, with secondary outcomes including GH control and tumor response. After 12 months of treatment, 50% of patients achieved IGF-1 normalization.
Abstract
<h4>Background/objectives</h4>Acromegaly is a chronic endocrine disorder caused mainly by GH-secreting pituitary adenomas, leading to excess GH and elevated IGF-1. Although surgery is first-line therapy, many patients require medical treatment, and remission is often not achieved with first-generation somatostatin receptor ligands (SRLs). Pasireotide, a second-generation SRL, offers superior biochemical and tumor control but is associated with hyperglycemia. This study aimed to evaluate real-world outcomes associated with pasireotide treatment in patients with acromegaly inadequately controlled on first-generation SRLs, with IGF-1 normalization as the primary endpoint. Secondary outcomes included GH control, tumor response, and glycemic safety.<h4>Methods</h4>We conducted a historical cohort study of adults with acromegaly treated at Clínica Imbanaco (Cali, Colombia) between 2017 and 2024. Eligible patients had residual tumors and persistently elevated GH and/or IGF-1 levels above the age-adjusted upper limit of normal despite treatment with clinically adequate doses of first-generation SRLs, as well as 12 months of continuous pasireotide treatment and follow-up after pasireotide initiation. Demographic, biochemical, imaging, and glycemic data were collected. Statistical analysis included paired and independent Student's <i>t</i>-tests, Wilcoxon signed-rank tests, McNemar's test, and Fisher's exact test, with significance set at <i>p</i> < 0.05.<h4>Results</h4>Fourteen patients (50% female; mean age 52.1 ± 14.5 years) were included. After 12 months, mean IGF-1 decreased from 2.73 ± 0.73 to 0.99 ± 0.56 × ULN, and 50% achieved IGF-1 normalization. Additionally, 35.7% achieved GH < 1 ng/mL, and 14.3% achieved combined control. Mean tumor diameter decreased by -3.26 mm (95% CI -4.56 to -1.95; <i>p</i> < 0.001). HbA1c increased from 5.56% to 6.05%, while type 2 diabetes mellitus prevalence rose from 14.3% to 35.7%. No patient discontinued pasireotide due to metabolic adverse events.<h4>Conclusions</h4>Pasireotide was associated with favorable biochemical and tumor responses in patients with acromegaly inadequately controlled on first-generation SRLs under real-world conditions. Although treatment was associated with higher HbA1c and increased diabetes incidence, proactive monitoring and early management of hyperglycemia may have supported treatment persistence.
Background
Acromegaly is primarily caused by GH-secreting pituitary adenomas, leading to excess GH and elevated IGF-1 levels. While surgery is the first-line treatment, many patients do not achieve remission with first-generation somatostatin receptor ligands (SRLs). This study investigates the real-world effectiveness of pasireotide, a second-generation SRL, in patients who remain inadequately controlled on first-generation SRLs, focusing on biochemical response and tumor reduction.
Methods
This historical cohort study involved 14 adults with acromegaly treated at Clínica Imbanaco in Cali, Colombia, from 2017 to 2024. Eligible patients had residual tumors and elevated GH/IGF-1 levels despite adequate treatment with first-generation SRLs. Participants received 12 months of pasireotide treatment, with outcomes including IGF-1 normalization, GH control, tumor response, and glycemic safety assessed through various statistical tests.
Results
After 12 months of pasireotide treatment, mean IGF-1 levels decreased significantly, with 50% of patients achieving normalization. Additionally, 35.7% of patients had GH levels below 1 ng/mL, and mean tumor diameter reduced by -3.26 mm (95% CI -4.56 to -1.95; p<0.001). However, HbA1c levels increased, and the prevalence of type 2 diabetes rose from 14.3% to 35.7%.
Interpretation
The findings suggest that pasireotide can lead to significant biochemical and tumor responses in patients with acromegaly, although the clinical significance of these changes should be considered alongside the observed increase in HbA1c and diabetes prevalence. The small sample size and lack of a control group limit the robustness of the conclusions, indicating the need for further studies to validate these results.
Key findings
- Mean IGF-1 decreased from 2.73 ± 0.73 to 0.99 ± 0.56 × ULN after 12 months, n=14.
- 50% achieved IGF-1 normalization after 12 months.
- Mean tumor diameter decreased by -3.26 mm (95% CI -4.56 to -1.95; p<0.001).
- HbA1c increased from 5.56% to 6.05% after 12 months.
- Type 2 diabetes mellitus prevalence rose from 14.3% to 35.7%.
Limitations
- small sample size n=14
- no control group
- single-site study
- short follow-up period of 12 months