Anagliptin monotherapy in patients with type 2 diabetes mellitus and high low-density lipoprotein cholesterol reduces fasting plasma lathosterol level: a single-arm intervention trial

Background. Anagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, has been shown to decrease low-density lipoprotein cholesterol (LDL-C) levels in plasma. Aim of study. The objective of our study is to elucidate the mechanisms responsible for anagliptin-mediated improvements in high LDL-C levels (hyper-LDL-C-emia). Methods. We prospectively examined the effects of anagliptin monotherapy on fasting plasma lathosterol, sitosterol, and campesterol levels in patients with type 2 diabetes mellitus and hyper-LDL-C-emia for 6 months. We examined 8 patients who did not use hypoglycemic or lipid-lowering drugs, other than anagliptin, for 4 months before initiating the study. Serum variables related to glucose and lipid metabolism were measured before and after the treatment for 6 months and pre- and post-prandially using the cookie-loading test. Results. After treatment, anagliptin monotherapy (n = 8) significantly decreased fasting LDL-C (182.8 to 167.8 mg/dL, as mean values of before and after the treatment) and plasma lathosterol levels (3.2 to 2.6 mg/dL); however, no significant changes were observed in fasting sitosterol or campesterol levels. Furthermore, a significant increase (p = 0.0012) in the change in 1-h post-prandial active glucagon-like peptide-1 (GLP-1) levels was observed after anagliptin treatment. For all participants (n = 17), fasting plasma lathosterol levels were negatively correlated with pre-prandial GLP-1 levels. Conclusion. Anagliptin monotherapy may have a beneficial effect on lipid metabolism, which is mediated by the inhibition of hepatic cholesterol synthesis, and not by the inhibition of intestinal lipid transport.