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 μg/mL vs. 52 weeks, 1.4 ± 1.0 μg/mL, p = 0.02), whereas it did not change in the anagliptin group (baseline, 1.3 ± 0.8 μg/mL vs. 52 weeks, 1.3 ± 0.7 μg/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 ://clini caltr ials.gov/ct2/show/NCT02 33040 6; registered January 5, 2015.

Lipid abnormalities, including hypertriglyceridemia, are one of the most common comorbidities in patients with chronic kidney disease (CKD) and are independently associated with disease progression. However, it remains uncertain whether treatment for hypertriglyceridemia has favorable effects on the clinical course of IgA nephropathy (IgAN). Pemafibrate is a novel selective peroxisome proliferator-activated receptor-alpha modulator and may be distinct from conventional fibrates in terms of its pharmacological activity and hepatic and renal safety. A recent clinical study demonstrated that pemafibrate was safe and effective for correcting pro-atherogenic lipid abnormalities in CKD patients with a wide range of renal insufficiency. However, the effect of pemafibrate on renal function in patients with IgAN and hypertriglyceridemia has not been verified. This paper is the first to show that 12 months of pemafibrate (0.1 mg daily) administration in three drug-naïve and mild IgAN patients with variable renal dysfunction and histopathology proven IgAN decreased serum triglyceride level and excretion of urinary protein and liver-type fatty acid-binding protein with no change in estimated glomerular filtration rate (eGFR). These findings suggest that pemafibrate is safe and effective for correcting hypertriglyceridemia and decreasing urinary protein excretion without changing eGFR and blood pressure levels in mild IgAN patients with hypertriglyceridemia.

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Sitagliptin treatment offers elderly patients aged ≥65 years efficacious and safe reductions in HbA1c values regardless of BMI. Geriatr Gerontol Int 2018; 18: 631-639.