Acromegaly treatment strategies with LA-SMSA and pegvisomant hypothesized to differentially impact gut hormones and postprandial metabolism

Acromegaly, a rare hormonal disorder, results from excess growth hormone (GH) secretion, leading to hepatic insulin-like growth factor 1 (IGF-1) hypersecretion. This condition, along with its treatments like long-acting somatostatin analogs (LA-SMSA) and pegvisomant, significantly impacts glucose and lipid metabolism, potentially increasing cardiovascular risk. Current understanding lacks detailed insights into how these treatments specifically modulate gut hormone physiology and postprandial substrate handling, highlighting a critical gap in optimizing metabolic outcomes for acromegaly patients.

This pilot study protocol outlines an investigation into insulin sensitivity, postprandial gut hormone response, lipid handling, and adipocytokine profiles across four cross-sectional groups: controlled acromegalic patients on LA-SMSA (Group 1), controlled patients on LA-SMSA and pegvisomant combination (Group 2), acromegalic patients controlled post-surgery without medical therapy (Group 3), and healthy controls (Group 4). Additionally, a longitudinal arm (Group 5) will explore uncontrolled acromegalic patients on LA-SMSA monotherapy before and three months after introducing pegvisomant to normalize IGF-1 levels. Key endpoints include insulin sensitivity, postprandial gut hormone response, lipid handling, and adipocytokine profile measurements.

This pilot study describes a clinical protocol and its specific hypotheses, as no results are yet available from the investigation. The primary hypothesis posits that lipid and glucose handling will be less efficient in controlled acromegalic patients receiving LA-SMSA monotherapy (Group 1) compared to those on LA-SMSA and pegvisomant combination treatment (Group 2) or patients who achieved control after surgery without medical therapy (Group 3). Specifically, the investigators anticipate differences in insulin sensitivity, postprandial gut hormone response, lipid handling, and adipocytokine profile across these groups. A further hypothesis suggests that there will be no significant difference in substrate metabolism between healthy control subjects (Group 4) and controlled acromegalic patients on combination treatment or those controlled post-surgery. Additionally, in a longitudinal arm (Group 5) of uncontrolled acromegalic patients, the introduction of pegvisomant is hypothesized to significantly improve their postprandial lipid and glucose handling, with assessments performed before and three months after IGF-1 normalization. These hypotheses guide the exploration of how different treatment modalities for Acromegaly impact crucial metabolic pathways.