Treatment of acromegaly-induced diabetes: an updated proposal

Abstract

Acromegaly-induced diabetes presents unique features due to the direct effects of excess growth hormone (GH) and insulin-like growth factor 1 (IGF-) on glucose metabolism, especially insulin resistance in association to low body fat content and water retention. Increased cardiovascular risk is much higher when acromegaly is complicated with diabetes, thus requiring a holistic management that addresses also these specific characteristics which differ from those of classical type 2 diabetes.The optimal management of diabetes in acromegaly requires not only an effective control of carbohydrate disturbances per se, but also the concurrent control of GH hypersecretion as it will directly impact on glucose control. If surgical treatment is not effective to normalize GH and IGF-1 levels, pharmacologic therapy for acromegaly must consider the metabolic effects that the different drugs may induce, as some of them may worsen carbohydrate metabolism. When treating acromegaly-induced diabetes, a comprehensive approach is essential, incorporating medications that may also protect against acromegaly associated comorbidities. Metformin remains the first-line therapy due to its ability to reduce hepatic glucose production enhance insulin sensitivity and its cost effectiveness. The newer drug classes, such as glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors, offer benefits similar to those seen in type 2 diabetes, but the unique metabolic profile of acromegaly-including an enhanced ketogenic state and the effects of incretins on GH secretion-have to be considered as it may influence outcomes. Understanding the distinct pathophysiology of acromegaly-induced diabetes and the benefits of these newer drug classes for the patient with acromegaly is crucial for optimizing treatment outcomes and improving the quality of life.

Keywords: Acromegaly; Diabetes; GLP-1; Guideline; Hyperglycemia; SGLT2i.