Effects of the glucagon-like peptide-1 (GLP-1) analogues exenatide, exenatide extended-release, and of the dipeptidylpeptidase-4 (DPP-4) inhibitor sitagliptin on glucose metabolism in healthy cats

Highlig hts
• The use of incretin mimetics and enhancers was investigated in healthy cats.
• Exenatide, exenatide extended-release, and sitagliptin were used.
• All three drugs enhanced meal-induced insulin secretion.
• Incretin-based therapy may represent a novel treatment option for diabetic cats.

Incretin analogues and inhibitors of the breakdown of endogenous incretins are antidiabetic drugs that increase β-cell proliferation and glucose-stimulated insulin secretion in rodents and humans. Objectives were to test whether exenatide, exenatide extended-release, and sitagliptin can be safely used in cats, to identify the most effective drug, and to test the effects of prolonged exenatide extended-release administration. Three cats each were given exenatide (0.2–2 µg/kg, q12h, subcutaneously, 5 days), exenatide extended-release (40–400 µg/kg, subcutaneously, once), and sitagliptin (1–10 mg/kg, q24h, orally, 5 days). Before and after treatment, glucose, insulin and glucagon areas under the curve (AUC) were assessed by meal response tests (MRT). Exenatide increased insulin AUC by 224%, 258%, 331% and 93%, exenatide extended-release by 127%, 169%, 178% and 95%, and sitagliptin by 32%, 69%, 62%, and 43%, respectively. The tested drugs are safe to use in cats and enhance insulin secretion. Incretin-based therapy may be beneficial in cats with diabetes mellitus.