Endocrine Abstracts

JOINT3912

background: Acromegaly, a condition caused by excess growth hormone (GH) secretion, often requires lifelong pharmacological treatment. Current therapies, including somatostatin receptor ligands (SRLs) and GH receptor antagonists (pegvisomant), are associated with high costs and accessibility challenges. Metformin, a widely used antidiabetic drug, was suggested to have potential benefits in endocrine disorders.

Objective: To evaluate metformin as an adjunctive therapy in non-diabetic patients with acromegaly.

Methods: we analyzed a case series of four male patients with acromegaly treated with SRL (n = 4) and/or pegvisomant (n = 2). Metformin (500mg-850mg) was added to their existing treatment regimens, and we monitored biochemical response (insulin-like growth factor I; IGF-I), glycemic control (HbA1C), and treatment costs for 3-6 months. Additionally, we assessed in vitro the action of metformin on pituitary GH, using a rat Gh promoter reporter vector and determining GH secretion from human GH-secreting pituitary tumors in primary cell culture (n = 11).

Results: All four patients were previously treated with SRLs (octreotide LAR or lanreotide) and two received in addition pegvisomant. Addition of metformin reduced IGF-I in all patients, and enabled dose adjustments of SRLs and pegvisomant that resulted in cost savings (EUR/month 482.80±289.88), while maintaining biochemical control. Glycemic control was maintained in all patients. One patient experienced improved gastrointestinal symptoms and weight loss (5kg). in vitro, metformin significantly reduced rGh promoter activity, and suppressed GH secretion beyond 20% in 6/11 primary cultures (% suppression 23±2.45). Addition of metformin to octreotide suppressed GH secretion in all cases (% GH suppression 36±6.49). In the in vitro-octreotide responder tumors, addition of metformin potentiated octreotide’s antisecretory action (% suppression 37±5.18 vs. 25±4.26).

Conclusion: This small case series study suggests that metformin addition to the currently standard SRL/pegvisomant treatment may be useful at improving biochemical control and reducing treatment costs in patients with acromegaly. Our in vitro data indicate a direct pituitary action for metformin on GH synthesis. Further large-scale studies are needed to evaluate the efficacy and safety of metformin as adjuvant treatment in non-diabetic patients with acromegaly.