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

Arai, Hidenori; Yamashita, Shizuya; Yokote, Koutaro; Araki, Eiichi; Suganami, Hideki; Ishibashi, Shun

doi:10.1016/j.atherosclerosis.2017.03.032

Cited by 112 publications

(79 citation statements)

References 46 publications

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“…The gamma‐glutamyl transpeptidase level significantly decreased and the ALT level decreased, although this change was not statistically significant, in the present study. Previous studies on the effects of pemafibrate reported significant decreases in both gamma‐glutamyl transpeptidase and ALT levels. Patients with non‐alcoholic fatty liver disease (NAFLD) have higher HOMA‐IR and/or lower GIR levels than those without NAFLD.…”

Section: Discussionmentioning

confidence: 99%

Effects of a novel selective peroxisome proliferator‐activated receptor‐α modulator, pemafibrate, on hepatic and peripheral glucose uptake in patients with hypertriglyceridemia and insulin resistance

Matsuba¹,

Matsuba

Ishibashi

et al. 2018

J of Diabetes Invest

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Aims/IntroductionPemafibrate is a novel selective peroxisome proliferator‐activated receptor‐α modulator with potent triglyceride‐lowering and high‐density lipoprotein cholesterol‐raising effects. We showed that pemafibrate decreased the homeostatic model assessment for insulin resistance in patients with dyslipidemia. To investigate how pemafibrate improves insulin sensitivity, we used a hyperinsulinemic‐euglycemic clamp technique to determine the splanchnic and peripheral glucose uptake in patients with hypertriglyceridemia and insulin resistance.Materials and MethodsA total of 27 patients with hypertriglyceridemia and insulin resistance were randomly assigned to receive pemafibrate (0.4 mg/day, b.i.d.) or placebo treatment for 12 weeks. The hyperinsulinemic‐euglycemic clamp test combined with oral glucose loading was carried out at weeks 0 and 12 to evaluate the splanchnic and peripheral glucose uptake.ResultsPemafibrate, but not the placebo, significantly increased the splanchnic glucose uptake rate from baseline (19.6 ± 5.9% with P = 0.005 and 2.1 ± 7.4% with P = 0.78, respectively), although no significant difference between the groups was observed (P = 0.084). Conversely, peripheral glucose uptake rate was not significantly altered. Pemafibrate, compared with the placebo, significantly decreased plasma triglycerides (−61.4 ± 16.4% vs −2.5 ± 41.4%, P = 0.001), free fatty acids (−24.8 ± 23.2% vs 2.0 ± 26.8%, P = 0.016) and gamma‐glutamyl transpeptidase (−30 ± 46 vs 10 ± 19 U/L, P = 0.009) levels, and significantly increased fibroblast growth factor 21 (457.7 ± 402.1 vs −41.7 ± 37.4 pg/mL, P = 0.007) levels.ConclusionsPemafibrate increased splanchnic glucose uptake from baseline in patients with hypertriglyceridemia.

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Section: Discussionmentioning

confidence: 99%

Effects of a novel selective peroxisome proliferator‐activated receptor‐α modulator, pemafibrate, on hepatic and peripheral glucose uptake in patients with hypertriglyceridemia and insulin resistance

Matsuba¹,

Matsuba

Ishibashi

et al. 2018

J of Diabetes Invest

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“…22 Phase 2 and 3 studies demonstrated that pemafibrate treatment, with or without statins, resulted in a significant decrease in fasting TG level and increase in HDL-C level and suggested that pemafibrate may have a superior risk/benefit profile to fenofibrate. [23][24][25][26][27] In vivo and in vitro studies found that pemafibrate enhanced CEC, RCT, and TRL catabolism, suppressed TRL production, and exerted anti-inflammatory and antiatherosclerotic effects. 28 Therefore, the present study aimed to investigate the effects of pemafibrate on CEC and postprandial hyperlipidemia in patients with atherogenic dyslipidemia.…”

Section: Introductionmentioning

confidence: 99%

Effects of pemafibrate (K-877) on cholesterol efflux capacity and postprandial hyperlipidemia in patients with atherogenic dyslipidemia

Yamashita

Arai

Yokote

et al. 2018

Journal of Clinical Lipidology

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“…Prospective studies are needed to demonstrate whether clinical interventions targeting [HDL‐C/apoA‐I] or other aspects of dyslipidaemia (which would otherwise improve this ratio and the derived indices) will decrease microvascular and/or macrovascular outcomes . Relevant interventions should a priori improve the ratio by a magnitude such as the one separating 2 quartiles, or ideally move this ratio by a value approaching the difference among 2 or even 3 ascending quartiles.…”

Section: Discussionmentioning

confidence: 99%

[HDL‐C/apoA‐I]: A multivessel cardiometabolic risk marker in women with T2DM

Hermans

Valensi

Ahn

et al. 2017

Diabetes Metabolism Res

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Aims: Although women have higher high-density lipoprotein cholesterol (HDL-C) than have men, their HDL particles are also prone to become small, dense, and dysfunctional in case of type 2 diabetes mellitus (T2DM). To assess the vascular risk related to HDLs of different sizes/densities without direct measurement, we adjusted HDL-C to its main apolipoprotein Results: An adverse cardiometabolic profile characterized QI and QII patients whose HDLs were denser and depleted in apoA-I, whereas QIII patients had HDLs with characteristics closer to those of controls. QIV patients had HDLs of supernormal size/composition and a more favourable phenotype in terms of fat distribution; insulin sensitivity (64% vs 41%), metabolic syndrome, and β-cell function (32% vs 23%); exogenous insulin (44 vs 89 U·d −1 ); and glycaemic control (glycated haemoglobin, 56 vs 61 mmol·mol −1 ), associated with lower prevalence of microvascular/macrovascular complications: all-cause microangiopathy 47% vs 61%; retinopathy 22% vs 34%; all-cause macroangiopathy 19% vs 31%; and coronary artery disease 6% vs 24% (P < .05). Conclusion:[HDL-C/apoA-I] can stratify T2DM women according to metabolic phenotype, macrovascular and coronary damage, β-cell function, microangiopathic risk, and retinopathy. This ratio is a versatile and readily available marker of cardiometabolic status and vascular complications in T2DM women.

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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

Abstract: These results strongly support the favourable benefit-to-risk ratio of K-877 add-on therapy in combination with statin treatment.

Cited by 112 publications

References 46 publications

Effects of a novel selective peroxisome proliferator‐activated receptor‐α modulator, pemafibrate, on hepatic and peripheral glucose uptake in patients with hypertriglyceridemia and insulin resistance

Effects of a novel selective peroxisome proliferator‐activated receptor‐α modulator, pemafibrate, on hepatic and peripheral glucose uptake in patients with hypertriglyceridemia and insulin resistance

Effects of pemafibrate (K-877) on cholesterol efflux capacity and postprandial hyperlipidemia in patients with atherogenic dyslipidemia

[HDL‐C/apoA‐I]: A multivessel cardiometabolic risk marker in women with T2DM

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