Differences in lipid metabolism between anagliptin and sitagliptin in patients with type 2 diabetes on statin therapy: a secondary analysis of the REASON trial.

ABSTRACT: BACKGROUND:Anagliptin, a dipeptidyl peptidase-4 inhibitor, is reported to reduce the level of low-density lipoprotein cholesterol (LDL-C). The underlying mechanism of this effect and effect on lipid metabolism however remains uncertain. AIM AND METHODS:We therefore evaluate the effects of anagliptin on lipid metabolism-related markers compared with those of sitagliptin. The study was a secondary analysis using data obtained from the Randomized Evaluation of Anagliptin versus Sitagliptin On low-density lipoproteiN cholesterol in diabetes (REASON) trial. This trial in patients with type 2 diabetes at a high risk of cardiovascular events and on statin therapy showed that anagliptin reduced LDL-C levels to a greater extent than sitagliptin. Cholesterol absorption (campesterol and sitosterol) and synthesis (lathosterol) markers were measured at baseline and 52 weeks in the study cohort (n?=?353). RESULTS:There was no significant difference in the changes of campesterol or sitosterol between the two treatment groups (p?=?0.85 and 0.55, respectively). Lathosterol concentration was increased significantly at 52 weeks with sitagliptin treatment (baseline, 1.2?±?0.7 ?g/mL vs. 52 weeks, 1.4?±?1.0 ?g/mL, p?=?0.02), whereas it did not change in the anagliptin group (baseline, 1.3?±?0.8 ?g/mL vs. 52 weeks, 1.3?±?0.7 ?g/mL, p?=?0.99). The difference in absolute change between the two groups showed a borderline significance (p?=?0.06). CONCLUSION:These findings suggest that anagliptin reduces LDL-C level by suppressing excess cholesterol synthesis, even in combination with statin therapy. Trial registration ClinicalTrials.gov number NCT02330406. https://clinicaltrials.gov/ct2/show/NCT02330406; registered January 5, 2015.

SUBMITTER: Chihara A 

PROVIDER: S-EPMC6858725 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature