Endocrine Abstracts

Context: Diabetes mellitus represents one of the most frequent metabolic comorbidities and occurs in 30% to 40% of patients with acromegaly. Patients with acromegaly develop insulin resistance due to GH excess, and in those with longstanding disease, insulin deficiency may occur. Moreover, the use of second-generation somatostatin receptor ligands (SRLs) pasireotide might contribute to the increased development in new-onset diabetes and the worsening of hyperglycemia. Management of type 2 diabetes (T2DM) has been revolutionized since the introduction of sodium-glucose cotransporter 2 inhibitors (SGLT2i) with their beneficial protective cardiovascular and renal effects in patients with and without diabetes. The current treatment recommendations for diabetes management in acromegaly are similar to the general population. However, the use of incretin-based therapy such as glucagon-like peptide-1 (GLP-1) agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors are more considered as second-line treatment modalities after metformin in patients with diabetes and acromegaly while the use of SGLT2i class is a less recommended option due to increased risk of diabetic ketoacidosis (DKA) in patients with acromegaly. We present our recommendations to define the position of SGLT2i in the treatment of diabetes in patients with acromegaly.

Evidence acquisition: Our recommendations are based on our experience with the use of SGLT2i in clinical practice in this subgroup of patients and the recently available published data.

Evidence synthesis: Acromegaly disease activity should be considered one of the important criteria for the management of diabetes in this subgroup of patients when considering treatment with SGLT2i. This criterion is driven by the fact that DKA was the initial manifestation in unrecognized active acromegaly according to recently published data. Thus, we recommend considering treatment with SGLT2i according to ADA, EASD, and ESC guidelines for patients with controlled acromegaly - defined as age- sex normalized IGF-1 levels, random GH < 1μg/liter, nadir GH after OGTT <0.4 μg/liter- that was achieved postoperatively with or without pharmacological treatment such as SSAs, GH receptor antagonist and dopamine agonists as monotherapy or in combination. For patients with active acromegaly treatment with incretin-based therapy as second-line therapy is more favorable, in such cases, the use of SGLT2i is less recommended due to increased tendency for DKA.

Conclusions: we recommend a more liberal strategy in using SGLT2i among patients with controlled acromegaly and diabetes. However, for patients with active acromegaly incretin-based therapy is more favorable.