Background

Pasireotide is a second-generation somatostatin receptor ligand (SRL) with proven efficacy for the treatment of acromegaly, although treatment-emergent hyperglycemia can occur. At present, there is an increasing interest in the role of a very-low-carbohydrate ketogenic diet in patients with acromegaly, which may exert insulin-induced IGF-1 normalization in combination with first-generation SRLs. Besides improving biochemical efficacy, this dietetic therapy may improve glycaemic metabolism as well. The objective of this Dutch multicenter RCT in acromegaly patients with pasireotide-induced hyperglycemia is to evaluate the difference in change in both HbA_1c and FPG from randomization to the end of the core study (4 months after randomization) between very-low carbohydrate ketogenic diet and diabetes medication.

Methods and design

Forthy acromegaly patients with pasireotide-induced hyperglycemia will be randomized 1:1 to open label very-low carbohydrate ketogenic diet or diabetes medication for 4 months. Subjects randomized to the eucaloric very-low carbohydrate ketogenic diet start with an ad libitum ketogenic diet of which only the amount of carbohydrates is restricted (<40 g of carbohydrate). Randomized subjects who reach the end of the randomized phase, can continue receiving pasireotide during an optional extension phase for another 4 months. Primary outcome measure is glycaemic control of pasireotide. Other outcome measures are sustainability of glycaemic control of pasireotide, as well as biochemical control, quality of life, tolerability and safety.

Discussion

In this first prospective study designed to assess the efficacy of very-low carbohydrate ketogenic diet versus diabetes medication for the management of pasireotide-associated hyperglycaemia in patients with acromegaly, we expect that a very-low carbohydrate ketogenic diet will be effective in improving glycaemic control and can show even a long-term effect on glucose regulation in patients with acromegaly.