Comparison of effects of anagliptin and alogliptin on serum lipid profile in type 2 diabetes mellitus patients

Abstract

IntroductionAnagliptin (ANA) improves dyslipidemia in addition to blood glucose levels. However, there are no comparative studies on the effects of ANA and other dipeptidyl peptidase‐4 inhibitors on serum lipid profile. We compared the effects of ANA on serum lipid profile with those of alogliptin (ALO) in type 2 diabetes mellitus outpatients.Materials and MethodsThe study participants were 87 type 2 diabetes mellitus patients who had been treated with dipeptidyl peptidase‐4 inhibitors for ≥8 weeks and had a low‐density lipoprotein cholesterol (LDL‐C) level of ≥120 mg/dL. Participants were switched to either 200 mg/day ANA or 25 mg/day ALO for 24 weeks.ResultsThere was no significant difference in percentage change in LDL‐C level at 24 weeks between the ANA and ALO groups. Treatment with ANA for 12 weeks significantly decreased LDL‐C levels, one of the secondary end‐points. Treatment with ANA for 24 weeks significantly improved apolipoprotein B‐100 levels, and the percentage change in LDL‐C levels at 24 weeks correlated significantly with the percentage change in apolipoprotein B‐100 levels in the ANA group.ConclusionsThe LDL‐C‐lowering effects of ANA and ALO at 24 weeks were almost similar in patients with type 2 diabetes mellitus. However, the results showed a tendency for a decrease in LDL‐C level at 24 weeks in the ANA group, and that such improvement was mediated, at least in part, through the suppression of apolipoprotein B‐100 synthesis.

Dipeptidyl peptidase 4 inhibitor anagliptin ameliorates hypercholesterolemia in hypercholesterolemic mice through inhibition of intestinal cholesterol transport

“…showed that in a comparison between alogliptin and anagliptin, only anagliptin exhibited a significant reduction of serum LDL‐C levels when a DPP‐4 inhibitor was changed from another DPP‐4 inhibitor in type 2 diabetes mellitus patients. Furthermore, anagliptin, but not alogliptin, significantly reduced serum ApoB‐100 levels after 24 weeks of treatment, suggesting that hepatic cholesterol synthesis might be suppressed by anagliptin. Similar effects of anagliptin on cholesterol synthesis in the liver were reported by others, and we also confirmed them, as mentioned above.…”

“…Because lipid metabolism could be closely related to glucose metabolism, and DPP‐4 inhibitors could affect glucose metabolism in diabetic animals, these studies using diabetic animals were considered to be difficult to confirm the direct effect of DPP‐4 inhibitors on lipid metabolism. First of all, we confirmed the lipid‐lowering effect of anagliptin in the mice, just as in a previous clinical study, with anagliptin treatment reducing the serum total cholesterol and non‐HDL‐C concentrations. Similar effects of anagliptin have been shown in ApoE‐deficient mice, LDL receptor knockout mice and cholesterol‐fed rabbits.…”

“…Regarding the differences of efficacy among DPP‐4 inhibitors, meta‐analysis suggests that the cholesterol‐lowering effect seems to be a ‘class effect’, and the present study shows the suppression of intestinal cholesterol transport would be DPP‐4‐dependent. However, Kurozumi et al . showed that in a comparison between alogliptin and anagliptin, only anagliptin exhibited a significant reduction of serum LDL‐C levels when a DPP‐4 inhibitor was changed from another DPP‐4 inhibitor in type 2 diabetes mellitus patients.…”

“…Similarly, alogliptin has been shown to significantly reduce the serum total cholesterol, non‐HDL‐C and LDL‐C levels in newly diagnosed drug‐naive type 2 diabetes mellitus patients. Anagliptin has been reported to reduce the serum total cholesterol and LDL‐C levels in Japanese type 2 diabetes mellitus patients with hyperlipidemia, suggesting that the drug also exerts a lipid‐lowering action, in addition to its antidiabetic effect. Recently, DPP‐4 inhibition with anagliptin was shown to suppress serum lathosterol, a clinical marker of cholesterol synthesis.…”

New perspective on type 2 diabetes, dyslipidemia and non‐alcoholic fatty liver disease

“…Dipeptidyl peptidase‐4 inhibitors are effective antihyperglycemic agents for type 2 diabetes. Treatment with the inhibitor, anagliptin, for 24 weeks to Japanese type 2 diabetes patients was shown to reduce plasma LDL‐C level, partly by suppressing apoB‐100 synthesis 5 . The effects were pronounced in type 2 diabetes patients with higher baseline LDL‐C levels, and a recent report suggested that it benefits lipid metabolism through dipeptidyl peptidase‐4‐dependent and glucagon‐like peptide‐1‐independent inhibition of intestinal cholesterol transport 6 .…”