Determinants of Bezafibrate-induced Improvements in LDL Cholesterol in Dyslipidemic Patients with Diabetes

Abstract

Aim:Our previous "J-BENEFIT (Japan BEzafibrate cliNical EFfectIveness and Tolerability)" study demonstrated that bezafibrate improves blood lipid profiles and glucose control in dyslipidemic patients with diabetes. However, bezafibrate did not significantly improve low-density lipoprotein cholesterol (LDL-C), although some patients showed decreases while others showed increases in the LDL-C levels. Therefore, a subgroup analysis of the J-BENEFIT study was conducted to identify factors influencing the bezafibrate-induced changes in the LDL-C levels. Methods: Of the 3,316 patients in the J-BENEFIT study, 2,116 not treated with other lipid-lowering drugs were enrolled in the current study, and the effects of 24-week treatment with bezafibrate on the LDL-C levels were analyzed. A reduction in the LDL-C level of ≥ 25% occurred in 253 patients, and a logistic-regression analysis was used to identify factors associated with this improvement. Results: Among the 2,116 overall patients, bezafibrate treatment significantly increased the LDL-C levels from 123.9 36.7 to 125.7 31.3 mg/dL. The subanalysis showed that the treatment responses varied according to the baseline LDL-C level, with significant decreases in the ≥ 160 and ≥ 140-160 mg/dL groups, no significant decrease in the ≥ 120-140 mg/dL group and a significant increase in the 120 mg/dL group. A multivariate logistic-regression analysis of the data for the patients with an LDL-C of ≥ 25% identified a female sex, the use of anti-hypertensive and hypoglycemic agents and a high baseline LDL-C level to be significant determinants of the LDL-C response to bezafibrate. Conclusions: Our results showed that treatment with bezafibrate improves the LDL-C levels and lipid profiles in dyslipidemic diabetic patients, especially women, subjects co-treated with anti-hypertensive or hypoglycemic agents and those with high baseline LDL-C levels. See editorial vol. 22: 658-659J Atheroscler Thromb, 2015; 22: 676-684.

Dapagliflozin decreases small dense low-density lipoprotein-cholesterol and increases high-density lipoprotein 2-cholesterol in patients with type 2 diabetes: comparison with sitagliptin

“…Conversely, the majority of studies have demonstrated that SGLT-2 inhibitors reduce TG and increase HDL-C levels, which reduce atherogenic risk [2, 22]. TG-lowering agents, such as fibrates and omega-3 fatty acids, have a tendency to increase LDL-C [23, 24] probably because of reduced lipid transfer between TG-rich lipoprotein (TRL)-TG and LDL-C [25]. Therefore, it is not surprising that reduced levels of TG associated with SGLT-2 inhibitor use resulted in suppressed generation of cholesterol-poor LDL particles.…”

Efficacy and safety of K-877, a novel selective peroxisome proliferator-activated receptor α modulator (SPPARMα), in combination with statin treatment: Two randomised, double-blind, placebo-controlled clinical trials in patients with dyslipidaemia

“…In the FIRST study, add-on administration of fenofibric acid with atorvastatin increased LDL-C by approximately 8% at 13 weeks and approximately 12% at 26 weeks, and a difference from that in the placebo group was also observed [23]. In the J-BENEFIT study, bezafibrate elevated LDL-C particularly in subgroups with lowbaseline LDL-C and high-baseline TG [24]. In the present studies, the percent change in LDL-C was positively correlated with baseline TG and inversely correlated with baseline LDL-C (data not shown), similar to the previous study [19].…”

Triglyceride/low-Density-Lipoprotein Cholesterol (TG/LDL-C) Ratio is the Most Diagnostically Valuable Predictor for Increased Small, Dense LDL in Type 2 Diabetes Patients

“…In the former group, TGs and sd-LDL were also higher than those in the latter group, but there was no difference in non-HDL-C between the two groups (4.9 [4.0-5.4] mmol/L vs. 4.8 [4.5-5.2] mmol/L) [9]. Alternatively, the increase in TGs and decrease in LDL-C (calculated using Friedewald's formula) could have been synchronized [13,32], and the change in non-HDL-C might have been offset. The non-HDL-C measurement formula evaluates the cholesterol levels of TGs and LDL, which are rich in apoB.…”