Dipeptidyl peptidase-4 inhibitor, anagliptin, alters hepatic insulin clearance in relation to the glycemic status in Japanese individuals with type 2 diabetes

Aims/Introduction This study investigated the impact of the dipeptidyl peptidase-4 inhibitor, anagliptin, on hepatic insulin clearance (HIC) in Japanese type 2 diabetes patients and explored its relationship to glycemic status. Materials and Methods Data on 765 participants in anagliptin phase 2 and 3 studies were analyzed. Adjusted changes in variables during 12 weeks of anagliptin therapy were compared with a placebo. HIC was calculated as the ratio, C-peptide area under the curve 0-120 min to insulin area under the curve 0-120 min, after a meal tolerance test. To explore the effects of baseline HIC levels on variables, participants receiving anagliptin were divided according to quartiles of baseline HIC. Furthermore, multivariate analysis investigated the association between baseline HIC levels and glycemic status. Results Anagliptin significantly reduced glycosylated hemoglobin levels (P < 0.001 vs placebo) and HIC levels (P < 0.01). Longer duration of diabetes, lower body mass index, higher glycosylated hemoglobin and lower insulin secretion capacity were observed with increases in baseline HIC levels. Improvements in glycosylated hemoglobin, glycoalbumin and 1,5-anhydroglucitol levels were greater in the relatively higher HIC group (baseline HIC levels >= median) than in the lower HIC group (<median). Conclusions Anagliptin affected HIC levels according to HIC baseline levels. Higher baseline HIC values might result in improved hyperglycemia through reduced HIC.