***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Objective —To assess whether adding a fibrate to statin therapy reduces residual cardiovascular risk associated with elevated triglycerides and low high-density lipoprotein cholesterol , The Evaluation of Choline Fenofibrate ( ABT-335 ) on Carotid Intima-Media Thickness ( cIMT ) in Subjects with Type IIb Dyslipidemia with Residual Risk in Addition to Atorvastatin Therapy ( FIRST ) trial evaluated the effects of fenofibric acid ( FA ) treatment on cIMT in patients with mixed dyslipidemia on atorvastatin . Approach and Results —This multicenter , double-blind , placebo-controlled study was performed in patients with mixed dyslipidemia ( fasting triglycerides , ≥150 mg/dL ; high-density lipoprotein cholesterol , ⩽45 [ men ] or 55 mg/dL [ women ] ; low-density lipoprotein cholesterol , ⩽100 mg/dL once and averaging ⩽105 mg/dL ) and a history of coronary heart disease or risk equivalent . Patients on background atorvastatin ( continued on starting dose or titrated to 40 mg , if needed ) were r and omized to FA 135 mg or placebo . The primary end point was rate of change from baseline through week 104 of the mean posterior-wall cIMT , measured by ultrasound . In patients with controlled low-density lipoprotein cholesterol while on atorvastatin background therapy , rate of change in posterior-wall cIMT was similar with FA plus atorvastatin ( −0.006 mm/y ) versus atorvastatin monotherapy ( 0.000 mm/y ; P=0.22 ) . FA plus atorvastatin was favored ( P<0.05 ) in 5 of 24 prespecified subgroups : age ≥60 years , history of coronary artery disease , cIMT > 0.795 mm , triglycerides 170 to 235 mg/dL , and statin use at entry . Adverse events were consistent with the known safety profiles of both drugs ; however , FA plus atorvastatin was associated with a greater incidence of renal-related adverse events compared with atorvastatin monotherapy ( 6.5 % versus 0.9 % ) . Conclusions —Compared with atorvastatin monotherapy , FA plus atorvastatin did not further decrease cIMT progression in high-risk patients with mixed dyslipidemia BACKGROUND AND AIMS To assess the efficacy and safety of K-877 ( Pemafibrate ) , a novel selective peroxisome proliferator-activated receptor α modulator ( SPPARMα ) that possesses unique PPARα activity and selectivity , compared with placebo and fenofibrate in dyslipidaemic patients with high triglyceride ( TG ) and low high-density lipoprotein cholesterol ( HDL-C ) levels . METHODS AND RESULTS This study was a double blind , placebo-controlled , parallel-group 12-week clinical trial . The study r and omized 224 patients to K-877  0.025 , 0.05 , 0.1 , 0.2 mg BID , fenofibrate 100 mg QD , or placebo ( 1:1:1:1:1:1 ) groups . Least squares mean percent changes from the baseline TG levels were -30.9 % , -36.4 % , -42.6 % , -42.7 % for the K-877 0.025 , 0.05 , 0.1 , 0.2 mg BID respectively ( p < 0.001 ) , which were greater than that of the fenofibrate 100 mg QD ( -29.7 % , p < 0.001 ) group . Statistically significant improvements from the baseline HDL-C , very-low-density lipoprotein cholesterol , chylomicron cholesterol , remnant lipoprotein cholesterol , apolipoprotein ( apo ) B ( apoB ) , and apoC-III were also observed in the K-877 groups . The incidence of adverse events ( AEs ) in the K-877 groups ( 32.4 - 56.8 % ) was comparable to those in placebo ( 47.2 % ) and fenofibrate 100 mg QD ( 56.8 % ) ; adverse drug reactions ( ADRs ) in the K-877 groups ( 2.7 - 5.4 % ) were less than those in placebo ( 8.3 % ) and fenofibrate 100 mg QD ( 10.8 % ) groups . CONCLUSION In dyslipidaemic patients with high TG and low HDL-C , K-877  improved TG , HDL-C , and other lipid parameters without increasing AEs or ADRs , compared to placebo and fenofibrate . K-877 can be expected to improve atherogenicity and to be a new beneficial treatment for dyslipidaemic patients BACKGROUND AND AIMS Substantial residual cardiovascular risks remain despite intensive statin treatment . Residual risks with high triglyceride and low high-density lipoprotein cholesterol are not the primary targets of statins . K-877 ( pemafibrate ) demonstrated robust efficacy on triglycerides and high-density lipoprotein cholesterol and a good safety profile as a monotherapy . The aim of these studies was to evaluate the efficacy and safety of K-877 add-on therapy to treat residual hypertriglyceridaemia during statin treatment . METHODS The objectives were investigated in two , multicentre , r and omised , double-blind ,  placebo-controlled  , parallel group comparison clinical trials : ( A ) K-877 0.1 , 0.2 , and 0.4 mg/day in combination with pitavastatin for 12 weeks in 188 patients , ( B ) K-877 0.2 ( fixed dose ) and 0.2 ( 0.4 ) ( conditional up-titration ) mg/day in combination with any statin for 24 weeks in 423 patients . RESULTS In both studies , we found a robust reduction in fasting triglyceride levels by approximately 50 % in all combination therapy groups , which was significant compared to the statin-monotherapy ( placebo ) groups ( p < 0.001 ) . High-performance liquid chromatography analysis for lipoprotein subfractions revealed that atherogenic lipoprotein profiles were ameliorated by K-877 add-on therapy , i.e. small low-density lipoproteins decreased whereas larger ones increased , and larger high-density lipoproteins decreased whereas smaller ones increased . The incidence rates of adverse events and adverse drug reactions in K-877 combination therapy groups were comparable to those in statin-monotherapy groups without any noteworthy event in both studies . CONCLUSIONS These results strongly support the favourable benefit-to-risk ratio of K-877 add-on therapy in combination with statin treatment Abstract Aims / Introduction Pemafibrate 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 . Material s and Methods A total of 27 patients with hypertriglyceridemia and insulin resistance were r and omly 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 . Results Pemafibrate , 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 . Conclusions Pemafibrate  increased splanchnic glucose uptake from baseline in patients with hypertriglyceridemia OBJECTIVE The development of new insulin sensitizers is an unmet need for the treatment of type 2 diabetes . We investigated the effect of GFT505 , a dual peroxisome proliferator – activated receptor (PPAR)-α/δ agonist , on peripheral and hepatic insulin sensitivity . RESEARCH DESIGN AND METHODS Twenty-two abdominally obese insulin-resistant males ( homeostasis model assessment of insulin resistance > 3 ) were r and omly assigned in a r and omized crossover study to subsequent 8-week treatment periods with GFT505 ( 80 mg/day ) or placebo , followed by a two-step hyperinsulinemic-euglycemic insulin clamp with a glucose tracer to calculate endogenous glucose production ( EGP ) . The primary end point was the improvement in glucose infusion rate ( GIR ) . Gene expression analysis was performed on skeletal muscle biopsy specimens . RESULTS GFT505  improved peripheral insulin sensitivity , with a 21 % ( P = 0.048 ) increase of the GIR at the second insulin infusion period . GFT505 also enhanced hepatic insulin sensitivity , with a 44 % ( P = 0.006 ) increase of insulin suppression of EGP at the first insulin infusion period . Insulin-suppressed plasma free fatty acid concentrations were significantly reduced on GFT505 treatment ( 0.21 ± 0.07 vs. 0.27 ± 0.11 mmol/L ; P = 0.006 ) . Neither PPARα nor PPARδ target genes were induced in skeletal muscle , suggesting a liver-targeted action of GFT505 . GFT505 significantly reduced fasting plasma triglycerides ( −21 % ; P = 0.003 ) and LDL cholesterol ( −13 % ; P = 0.0006 ) , as well as liver enzyme concentrations ( γ-glutamyltranspeptidase : −30.4 % , P = 0.003 ; alanine aminotransferase : −20.5 % , P = 0.004 ) . There was no safety concern or any indication of PPARγ activation with GFT505 . CONCLUSIONS The dual PPARα/δ agonist GFT505 is a liver-targeted insulin-sensitizer that is a promising drug c and i date for the treatment of type 2 diabetes and nonalcoholic fatty liver disease UNLABELLED Nonalcoholic fatty liver disease ( NAFLD ) covers a spectrum of liver damage ranging from simple steatosis to nonalcoholic steatohepatitis ( NASH ) , fibrosis , and cirrhosis . To date , no pharmacological treatment is approved for NAFLD/NASH . Here , we report on pre clinical and clinical data with GFT505 , a novel dual peroxisome proliferator-activated receptor alpha/delta ( PPAR-α/δ ) agonist . In the rat , GFT505 concentrated in the liver with limited extrahepatic exposure and underwent extensive enterohepatic cycling . The efficacy of GFT505 was assessed in animal models of NAFLD/NASH and liver fibrosis ( Western diet [WD]-fed human apolipoprotein E2 [ hApoE2 ] transgenic mice , methionine- and choline-deficient diet-fed db/db mice , and CCl4 -induced fibrosis in rats ) . GFT505  demonstrated liver-protective effects on steatosis , inflammation , and fibrosis . In addition , GFT505  improved liver dysfunction markers , decreased hepatic lipid accumulation , and inhibited proinflammatory ( interleukin-1 beta , tumor necrosis factor alpha , and F4/80 ) and profibrotic ( transforming growth factor beta , tissue inhib 
    Output:
    
Conclusions The lipid profile significantly improved in the pemafibrate group than in the placebo group .
In addition to the pemafibrate group having an improved lipid profile , which was comparable with that of the fenofibrate group , the AEs were significantly lower than in the fenofibrate group and an improvement in hepatobiliary enzyme activity was also recognized .