Effects of Pemafibrate, a Novel Selective PPARα Modulator, on Lipid and Glucose Metabolism in Patients With Type 2 Diabetes and Hypertriglyceridemia: A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial

Araki, Eiichi; Yamashita, Shizuya; Arai, Hidenori; Yokote, Koutaro; Satoh, Jo; Inoguchi, Toyoshi; Nakamura, Jiro; Maegawa, Hiroshi; Yoshioka, Narihito; Tanizawa, Yukio; Watada, Hirotaka; Suganami, Hideki; Ishibashi, Shun

doi:10.2337/dc17-1589

Cited by 135 publications

(105 citation statements)

References 39 publications

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“…After treatment period 1, treatment period 2 was initiated, from week 24 to week 52, with the placebo changed to 0.2 mg/d pemafibrate. The main results from treatment period 1 have been reported previously . This report summarizes the results including treatment period 2, which spanned 52 weeks.…”

Section: Introductionmentioning

confidence: 71%

“…Figure S2 shows the disposition of participants. Participant characteristics have been reported previously …”

Section: Resultsmentioning

confidence: 99%

“…The efficacy of pemafibrate on lipid profiles seems to be similar for both 0.2 mg/d and 0.4 mg/d; however, in the pooled analyses of six placebo‐controlled trials with pemafibrate, pemafibrate 0.4 mg/d lowered TG‐rich lipoproteins, ApoCIII, fasting plasma glucose, insulin, GGT and ALP to a greater extent than pemafibrate 0.2 mg/d . Cholesterol content in small‐sized HDL, which is thought to be more anti‐atherogenic, increased to a greater degree when treated with pemafibrate 0.4 mg/d than with pemafibrate 0.2 mg/d . Based on the above results, pemafibrate 0.4 mg/d seems to be more efficient in reducing atherosclerotic cardiovascular disease than pemafibrate 0.2 mg/d.…”

Section: Discussionmentioning

confidence: 96%

“…The study methods have been reported previously . Briefly, patients with type 2 diabetes and hypertriglyceridemia (TG levels ≥150 mg/dL [1.7 mmol/L] and ≤1000 mg/dL [11.3 mmol/L]) were treated with placebo or pemafibrate at a dose of 0.2 or 0.4 mg/d (twice daily) for 24 weeks.…”

Section: Methodsmentioning

confidence: 99%

“…Pemafibrate, a novel selective PPARα modulator (SPPARMα), has potent TG‐lowering and HDL cholesterol‐increasing activities, almost no effect on serum creatinine levels, and an ameliorating effect on liver function test values . Furthermore, it has high efficacy at low doses and is safe for clinical use, similarly to placebo …”

Section: Introductionmentioning

confidence: 99%

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Efficacy and safety of pemafibrate in people with type 2 diabetes and elevated triglyceride levels: 52‐week data from the PROVIDE study

Araki

Yamashita

Arai

et al. 2019

Diabetes Obesity Metabolism

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The aim of this study was to evaluate the efficacy and safety of pemafibrate in people with type 2 diabetes and hypertriglyceridaemia over a 52‐week period. Participants were randomly assigned to receive treatment with placebo or pemafibrate at a dose of 0.2 or 0.4 mg/d for 24 weeks (treatment period 1). The main results from treatment period 1 have been reported previously. The assigned treatment was continued up to week 52, except that the placebo was changed to pemafibrate 0.2 mg/d after week 24 (treatment period 2). The percentage changes in fasting serum triglyceride (TG) levels at week 52 (last observation carried forward) were −48.2%, −42.3%, and −46.4% in the placebo/pemafibrate 0.2 mg/d (n = 57), pemafibrate 0.2 mg/d (n = 54), and pemafibrate 0.4 mg/d (n = 55) groups, respectively. Levels of TG, non‐HDL cholesterol and total cholesterol stably decreased, whereas levels of HDL cholesterol increased with pemafibrate treatments over 52 weeks. Pemafibrate was well tolerated throughout the study period. The present study is the first to show that pemafibrate treatment substantially ameliorated lipid abnormalities and was well tolerated for 52 weeks in people with type 2 diabetes and hypertriglyceridaemia.

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Section: Introductionmentioning

confidence: 71%

“…Figure S2 shows the disposition of participants. Participant characteristics have been reported previously …”

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 96%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Efficacy and safety of pemafibrate in people with type 2 diabetes and elevated triglyceride levels: 52‐week data from the PROVIDE study

Araki

Yamashita

Arai

et al. 2019

Diabetes Obesity Metabolism

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Rounding the corner on residual risk: Implications of REDUCE‐IT for omega‐3 polyunsaturated fatty acids treatment in secondary prevention of atherosclerotic cardiovascular disease

Baum

Scholz

2019

Clinical Cardiology

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Patients with established atherosclerotic cardiovascular (CV) disease remain at increased risk of major adverse cardiovascular events even during optimal lipid‐lowering therapy. Recent studies using the methods of Mendelian randomization, as well as analyses of data from large statin trials, have concluded that elevated triglyceride (TG) levels contribute to that increased risk. Omega‐3 polyunsaturated fatty acids (omega‐3 PUFAs) from fish and shellfish (eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) reduce TG levels when added to the diet in sufficient amounts, and they have favorable effects on several other markers of CV risk. However, trials of omega‐3 PUFAs have had inconsistent findings regarding CV risk reduction. Recently, the REDUCE‐IT (Reduction of Cardiovascular Events with EPA‐Intervention Trial) trial reported that treatment of such high‐risk patients with icosapent ethyl, a purified and stabilized ethyl ester of EPA, reduced the risk of the trial's primary CV endpoint by 25% (95% confidence intervals [CI], 32%‐17%; P < .001). To appreciate the clinical implications of this result, it is important to understand how the REDUCE‐IT trial differed from previous trials, especially with regard to patient enrollment criteria and treatment dosing. We discuss these design features relative to other trials. TG lowering can account for only part of the risk reduction seen with icosapent ethyl; we also consider other potential contributory mechanisms.

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Therapeutic Agents Targeting Cardiometabolic Risk for Preventing and Treating Atherosclerotic Cardiovascular Diseases

Arsenault

Perrot

Puri

2018

Clin Pharma and Therapeutics

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Targeting atherogenic lipoprotein levels with statins remains the current cornerstone of atherosclerotic cardiovascular disease (ACVD) management. In patients at high ACVD risk who cannot achieve the desired low-density lipoprotein (LDL) cholesterol target, the addition of compounds such as ezetimibe and proprotein subtilisin/kexin type-9 (PCSK9) inhibitors incrementally lowers cardiovascular risk. New glucose-lowering drugs such as glucacon-like peptide-1 receptor (GLP1R) agonists and sodium-glucose cotransporter-2 (SGLT2) inhibitors were also shown to improve cardiometabolic risk factors and provide cardiovascular benefits in patients with type 2 diabetes. Our objective is to review the role of these agents in the management of patients at high ACVD risk and introduce new and (re)-emerging drugs targeting atherogenic lipoproteins such as LDL (inclisiran, bempedoic acid, etc.), remnant-like particles (fibrates, volanesorsen, and angiopoietin-like protein-3 (ANGPTL3) inhibitors), and lipoprotein(a) (AKCEA-APO[A]L ). The potential role of drugs targeting inflammation (canakinumab, methotrexate, and colchicine) in ACVD risk prevention/management will also be discussed.

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Effects of Pemafibrate, a Novel Selective PPARα Modulator, on Lipid and Glucose Metabolism in Patients With Type 2 Diabetes and Hypertriglyceridemia: A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial

Abstract: Pemafibrate significantly ameliorated lipid abnormalities and was well tolerated in patients with type 2 diabetes comorbid with hypertriglyceridemia.

Cited by 135 publications

References 39 publications

Efficacy and safety of pemafibrate in people with type 2 diabetes and elevated triglyceride levels: 52‐week data from the PROVIDE study

Efficacy and safety of pemafibrate in people with type 2 diabetes and elevated triglyceride levels: 52‐week data from the PROVIDE study

Rounding the corner on residual risk: Implications of REDUCE‐IT for omega‐3 polyunsaturated fatty acids treatment in secondary prevention of atherosclerotic cardiovascular disease

Therapeutic Agents Targeting Cardiometabolic Risk for Preventing and Treating Atherosclerotic Cardiovascular Diseases

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