Effects of lixisenatide treatment on mild cachexia and related metabolic abnormalities in Walker‐256 tumour‐bearing rats

Abstract

Lixisenatide, a glucagon‐like peptide‐1 (GLP‐1) receptor agonist, is used in the treatment of type 2 diabetes mellitus (T2DM). It increases insulin (INS) secretion and can decrease INS resistance, improving metabolic disorders in this disease. However, its effects on metabolic disturbances in cancer‐bearing, which also exhibit decreased INS secretion and INS resistance, changes that may contribute to weight loss (cachexia), have not yet been evaluated. The purpose of this study was to investigate the lixisenatide treatment effects on mild cachexia and related metabolic abnormalities in Walker‐256 tumour‐bearing rats. Lixisenatide (50 μg kg−1, SC) was administered once daily, for 6 days, after inoculation of Walker‐256 tumour cells. Acute lixisenatide treatment did not improve hypoinsulinemia, INS secretion and INS resistance of tumour‐bearing rats. It also did not prevent the reduced glucose and increased triacylglycerol and lactate in the blood and nor the loss of retroperitoneal and epididymal fat of these animals. However, acute lixisenatide treatment accentuated the body mass loss of tumour‐bearing rats. Therefore, lixisenatide, unlike T2DM, does not improve hypoinsulinemia and INS resistance associated with cancer, evidencing that it does not have the same beneficial effects in these two diseases. In addition, lixisenatide aggravated weight loss of tumour‐bearing rats, suggesting that its use for treatment of T2DM patients with cancer should be avoided. Significance of the study Lixisenatide increases insulin secretion and appears to reduce insulin resistance in T2DM. However, lixisenatide treatment does not improve hypoinsulinemia and insulin resistance associated with cancer, as it does in T2DM, and aggravated weight loss, suggesting that its use for treatment of T2DM patients with cancer should be avoided.