Endocrine Abstracts

Objective: There has been no consensus on the medical management of diabetes in acromegaly patients. The primary approach is like the general population, and metformin is considered first-line therapy. Sodium-glucose cotransporter inhibitors (SGLT2is) are a novel antidiabetic class which has an improving effect on insulin resistance. There is no recommendation regarding their use for diabetic acromegaly patients despite their potential beneficial effects by inducing glucosuria, osmatic diuresis, and cardiovascular safety. Euglycemic diabetic ketoacidosis might constitute a barrier related to insulin deficiency since GH per se increases lipid oxidation and ketone bodies. A recent pilot study showed the ability of an adjuvant Eucaloric very-low-carbohydrate ketogenic diet controlled IGF-I levels in patients with acromegaly whose disease was uncontrolled with first-generation somatostatin receptor ligand therapy¹. Thus, we aimed to evaluate the outcomes of SGLT2is on diabetes control, also control of IGF-1 levels in a subset of acromegaly patients.

Methods: We conducted a proof-of-concept study involving 6 patients (3 women, 3 men) to investigate whether a 3-month, SGLT2 is as adjuvant treatment to metformin (if not contraindicated) would affect IGF-I concentrations besides glucose parameters in patients with uncontrolled acromegaly. The treatment of acromegaly remained stable during the intervention.

Results: We showed a decrease in mean glucose, Hemoglobin A1C (HbA1c), and insulin-like growth factor 1 (IGF-1) levels. Body weight also showed a pattern of decline. Although blood ketone levels did not increase, serum creatinine levels showed an increasing trend. We had to withdraw a patient do the increased creatinine level (Table 1).

Conclusion: İt is noteworthy that a patient-tailored approach should be initiated not only for managing acromegaly and diabetes separately but also for combining therapies to enhance the effects. Although SGLT-2 inhibitors seem to have favorable effects on acromegaly patients, a caution on renal functions should be considered. Far-reaching studies are needed to evaluate the utility and adverse effects of this unique antidiabetic class in acromegaly patients.

Reference: 1. Coopmans EC, Berk KAC, El-Sayed N, Neggers S, van der Lely AJ. Eucaloric Very-Low-Carbohydrate Ketogenic Diet in Acromegaly Treatment. N Engl J Med. 2020;382(22):2161-2.