human
***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: Summary Aim : To evaluate the effect of ezetimibe on insulin sensitivity and lipid profile in obese and dyslipidaemic patients . Methods : A r and omized , double-blind , placebo-controlled clinical trial was carried out in 12 obese , dyslipidaemic patients , independently of their basal insulin sensitivity . At the beginning of the study , a metabolic profile was measured , and insulin sensitivity estimated using the euglycaemic-hyperinsulinaemic clamp technique . The volunteers were r and omly assigned to receive ezetimibe ( 10 mg/day in the morning ) or placebo for a period of 90 days . After intervention , a similar metabolic profile was measured and a second clamp study was performed . Results : Ezetimibe administration for 90 days decreased total ( 6.0 ± 0.5 vs. 4.2 ± 0.9 mmol/L , p = 0.011 ) and low-density lipoprotein ( 4.0 ± 0.7 vs. 2.2 ± 0.8 mmol/L , p=0.003 ) cholesterol concentrations without modification of insulin sensitivity ( 3.0 ± 0.6 vs. 2.9 ± 0.7 mg/kg/min , p = 0.345 ) . Conclusions : Ezetimibe significantly decreased total cholesterol and low-density lipoprotein cholesterol concentrations without affecting insulin sensitivity in obese and dyslipidaemic patients Objective . To evaluate the effects of ezetimibe/simvastatin ( EZE/SIMV ) and rosuvastatin ( ROSUV ) on oxidative stress ( OS ) markers in patients with diabetic polyneuropathy ( DPN ) . Methods . We performed a r and omized , double-blind , placebo-controlled phase III clinical trial in adult patients with Type 2 Diabetes Mellitus ( T2DM ) and DPN , as evaluated by composite scores and nerve conduction studies ( NCS ) . Seventy-four subjects with T2DM were allocated 1 : 1 : 1 to placebo , EZE/SIMV 10/20 mg , or ROSUV 20 mg for 16 weeks . All patients were assessed before and after treatment : primary outcomes were lipid peroxidation ( LPO ) , and nitric oxide ( NO ) surrogate levels in plasma ; secondary outcomes included NCS , neuropathic symptom scores , and metabolic parameters . Data were expressed as mean ± SD or SEM , frequencies , and percentages ; we used nonparametric analysis . Results . LPO levels were reduced in both statin arms after 16 weeks of treatment ( p < 0.05 versus baseline ) , without changes in the placebo group . NO levels were not significantly affected by statin treatment , although a trend towards significance concerning increased NO levels was noted in both statin arms . No significant changes were observed for the NCS or composite scores . Discussion . EZE/SIMV and ROSUV are superior to placebo in reducing LPO in subjects with T2DM suffering from polyneuropathy . This trial is registered with NCT02129231 AIM Ezetimibe selectively blocks intestinal cholesterol absorption by inhibiting Niemann-Pick C1-like 1 ( NPC1L1 ) and reducing LDL cholesterol ( LDL-C ) . In animals , ezetimibe reversed diet-induced obesity , liver steatosis , and insulin resistance . In humans , its potential effects on liver steatosis and insulin resistance have been suggested . We investigated the effects of ezetimibe on postpr and ial hyperlipidaemia and hyperglycaemia in obese subjects with dyslipidaemia in a double-blind r and omized crossover trial . METHODS Twenty obese men with hypertriglyceridaemia were assigned r and omly to an ezetimibe- or a placebo-precedence-treated group . Subjects in the ezetimibe group were treated with ezetimibe ( 10 mg/day ) for the first 4 weeks , followed by a 4-week interval and then treated with placebo for another 4 weeks . The placebo group received these treatments in reverse order . Subjects were requested to fast for at least 12 hours and then received a st and ard meal . Blood sample s were collected at 0 , 30 , 60 , 120 , 240 , 360 and 480 minutes after the meal on Days 0 , 28 , 56 and 84 and were used to measure the lipid and glucose metabolism markers . RESULTS Ezetimibe significantly decreased the postpr and ial serum triglyceride excursion ( p=0.01 ) and fasting serum LDL-C , remnant-like particles(RLP ) and ApoB48 levels ( p<0.05 ) . Postpr and ial glucose excursion , serum insulin levels , serum glucose-dependent insulinotropic polypeptide ( GIP ) and active glucagon-like peptide-1 ( GLP-1 ) were not significantly affected by ezetimibe treatment . CONCLUSION Ezetimibe restored the postpr and ial dysregulation of lipid but did not affect glucose metabolism in a double-blind r and omized crossover trial OBJECTIVE To assess the effects of inhibited gastrointestinal cholesterol absorption in statin-treated dyslipidemic patients . RESEARCH DESIGN AND METHODS In a multicenter prospect i ve r and omized double-blind placebo-controlled trial , we primarily compared by ANCOVA the effect of 2-month ezetimibe ( 10 mg/day ) or placebo therapy on LDL cholesterol serum levels in 108 type 2 diabetic patients with albuminuria < 200 μg/min and total cholesterol concentrations > 135 mg/dl despite simvastatin treatment ( 40 mg/day ) . RESULTS Unlike placebo , ezetimibe  decreased LDL cholesterol from 99 ± 31 to 66 ± 22 mg/dl , total cholesterol from 162 ± 36 to 124 ± 30 mg/dl , and apolipoprotein B from 83 ± 22 to 64 ± 18 mg/dl ( P < 0.0001 for all changes versus placebo ) . A total of 72 and 17 % of patients on ezetimibe or placebo  achieved LDL levels < 70 mg/dl , respectively ( P < 0.0001 ) . Treatment was well tolerated . CONCLUSIONS Adding ezetimibe to simvastatin therapy helps to improve the pro-atherogenic lipoprotein profile in type 2 diabetic patients who fail to reach recommended lipid targets with statin therapy alone Background It has been demonstrated that statins can increase intestinal sterol absorption . Augments in phytosterolemia seems related to cardiovascular disease . Objective We examined the role of soluble fiber intake in endogenous cholesterol synthesis and in sterol absorption among subjects under highly effective lipid-lowering therapy . Design In an open label , r and omized , parallel- design study with blinded endpoints , subjects with primary hypercholesterolemia ( n = 116 ) were assigned to receive during 12 weeks , a daily dose of 25 g of fiber ( corresponding to 6 g of soluble fibers ) plus rosuvastatin 40 mg ( n = 28 ) , rosuvastatin 40 mg alone ( n = 30 ) , sinvastatin 40 mg plus ezetimibe 10 mg plus 25 g of fiber ( n = 28 ) , or sinvastatin 40 mg plus ezetimibe 10 mg ( n = 30 ) alone . Results The four assigned therapies produced similar changes in total cholesterol , LDL-cholesterol , and triglycerides ( p < 0.001 vs. baseline ) and did not change HDL-cholesterol . Fiber intake decreased plasma campesterol ( p < 0.001 vs. baseline ) , particularly among those patients receiving ezetimibe ( p < 0.05 vs. other groups ) , and β-sitosterol ( p = 0.03 vs. baseline ) , with a trend for lower levels in the group receiving fiber plus ezetimibe ( p = 0.07 ) . Treatment with rosuvastatin alone or combined with soluble fiber was associated with decreased levels of desmosterol ( p = 0.003 vs. other groups ) . Compared to non-fiber supplemented individuals , those treated with fibers had weight loss ( p = 0.04 ) , reduced body mass index ( p = 0.002 ) and blood glucose ( p = 0.047 ) . Conclusion Among subjects treated with highly effective lipid-lowering therapy , the intake of 25 g of fibers added favorable effects , mainly by reducing phytosterolemia . Additional benefits include improvement in blood glucose and anthropometric parameters Background Statins are used to treat hypercholesterolemia in patients with type 2 diabetes mellitus , but many of these patients fail to achieve the target LDL-C level . Recent reports have suggested that a synergistic effect can be obtained by concomitant administration of the cholesterol absorption inhibitor ezetimibe and a statin . However , in patients with type 2 diabetes who are already being treated with satins , it remains unclear whether it is more effective to add ezetimibe or to increase the statin dose . Therefore , this study was performed to examine the effects of these two regimens on LDL-C and lipoproteins . Methods The subjects were type 2 diabetic patients under treatment with rosuvastatin ( 2.5 mg daily ) , who had LDL-C levels ≥80 mg/dL. They were r and omly allocated to a group that received add-on therapy with ezetimibe at 10 mg/day ( combination group , n = 40 ) or an increase of the rosuvastatin dose to 5 mg/day ( dose escalation group , n = 39 ) . These two groups were compared at baseline and after 12 weeks of treatment . Results The percent change of LDL-C was −31 % in the combination group and −12 % in the dose escalation group . Both groups showed a significant decrease , but the decrease was greater in the combination group . In both groups , there was a significant decrease in the levels of small dense LDL-C , oxidized LDL and remnant-like lipoprotein cholesterol . For all of these parameters , the percent changes were greater in the combination group . Only the combination group showed a significant decrease of triglycerides . Multivariate analysis was performed to identify factors associated with reaching an LDL-C level < 80 mg/dL. As a result , add-on therapy with ezetimibe was extracted as a factor related to improvement of LDL-C. Conclusions Compared with increasing the dose of rosuvastatin , the combination of rosuvastatin and ezetimibe not only achieves quantitative but also qualitative improvement of serum lipid levels in type 2 diabetic patients , suggesting that this combination could suppress the progression of atherosclerosis . Trial registration Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Summary Aim We aim ed to compare the effects of fixed‐dose combinations of ezetimibe plus rosuvastatin to rosuvastatin alone in patients with primary hypercholesterolemia , including a subgroup analysis of patients with diabetes mellitus ( DM ) or metabolic syndrome ( MetS ) . Method This multicenter eight‐week r and omized double‐blind phase III study evaluated the safety and efficacy of fixed‐dose combinations of ezetimibe 10 mg plus rosuvastatin , compared with rosuvastatin alone in patients with primary hypercholesterolemia . Four hundred and seven patients with primary hypercholesterolemia who required lipid‐lowering treatment according to the ATP III guideline were r and omized to one of the following six treatments for 8 weeks : fixed‐dose combinations with ezetimibe 10 mg daily plus rosuvastatin ( 5 , 10 , or 20 mg daily ) or rosuvastatin alone ( 5 , 10 , or 20 mg daily ) . Results Fixed‐dose combination of ezetimibe plus rosuvastatin significantly reduced LDL cholesterol , total cholesterol , and triglyceride levels compared with rosuvastatin alone . Depending on the rosuvastatin dose , these fixed‐dose combinations of ezetimibe plus rosuvastatin  provided LDL cholesterol , total cholesterol , and triglyceride reductions of 56%–63 % , 37%–43 % , and 19%–24 % , respectively . Moreover , the effect of combination treatment on cholesterol levels was more pronounced in patients with DM or MetS than in non‐DM or non‐MetS patients , respectively , whereas the effect of rosuvastatin alone did not differ between DM vs non‐DM or MetS vs non‐MetS patients . Conclusion Fixed‐dose combinations of ezetimibe and rosuvastatin provided significantly superior efficacy  to rosuvastatin alone in lowering LDL cholesterol , total cholesterol , and triglyceride levels . Moreover , the reduction rate was greater in patients with DM or Objective . To investigate the effect of ezetimibe on the insulin secretion in db/db mice . Methods . The db/db diabetic mice aged 8 weeks were r and omly assigned into 2 groups and intragastrically treated 
    Output:
    
agent
Conclusions Compared with high-dose statin therapy , ezetimibe with low-dose statin for more than 3 months may have a beneficial tendency of effects on glycemic control
***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: Summary Aim : To evaluate the effect of ezetimibe on insulin sensitivity and lipid profile in obese and dyslipidaemic patients . Methods : A r and omized , double-blind , placebo-controlled clinical trial was carried out in 12 obese , dyslipidaemic patients , independently of their basal insulin sensitivity . At the beginning of the study , a metabolic profile was measured , and insulin sensitivity estimated using the euglycaemic-hyperinsulinaemic clamp technique . The volunteers were r and omly assigned to receive ezetimibe ( 10 mg/day in the morning ) or placebo for a period of 90 days . After intervention , a similar metabolic profile was measured and a second clamp study was performed . Results : Ezetimibe administration for 90 days decreased total ( 6.0 ± 0.5 vs. 4.2 ± 0.9 mmol/L , p = 0.011 ) and low-density lipoprotein ( 4.0 ± 0.7 vs. 2.2 ± 0.8 mmol/L , p=0.003 ) cholesterol concentrations without modification of insulin sensitivity ( 3.0 ± 0.6 vs. 2.9 ± 0.7 mg/kg/min , p = 0.345 ) . Conclusions : Ezetimibe significantly decreased total cholesterol and low-density lipoprotein cholesterol concentrations without affecting insulin sensitivity in obese and dyslipidaemic patients Objective . To evaluate the effects of ezetimibe/simvastatin ( EZE/SIMV ) and rosuvastatin ( ROSUV ) on oxidative stress ( OS ) markers in patients with diabetic polyneuropathy ( DPN ) . Methods . We performed a r and omized , double-blind , placebo-controlled phase III clinical trial in adult patients with Type 2 Diabetes Mellitus ( T2DM ) and DPN , as evaluated by composite scores and nerve conduction studies ( NCS ) . Seventy-four subjects with T2DM were allocated 1 : 1 : 1 to placebo , EZE/SIMV 10/20 mg , or ROSUV 20 mg for 16 weeks . All patients were assessed before and after treatment : primary outcomes were lipid peroxidation ( LPO ) , and nitric oxide ( NO ) surrogate levels in plasma ; secondary outcomes included NCS , neuropathic symptom scores , and metabolic parameters . Data were expressed as mean ± SD or SEM , frequencies , and percentages ; we used nonparametric analysis . Results . LPO levels were reduced in both statin arms after 16 weeks of treatment ( p < 0.05 versus baseline ) , without changes in the placebo group . NO levels were not significantly affected by statin treatment , although a trend towards significance concerning increased NO levels was noted in both statin arms . No significant changes were observed for the NCS or composite scores . Discussion . EZE/SIMV and ROSUV are superior to placebo in reducing LPO in subjects with T2DM suffering from polyneuropathy . This trial is registered with NCT02129231 AIM Ezetimibe selectively blocks intestinal cholesterol absorption by inhibiting Niemann-Pick C1-like 1 ( NPC1L1 ) and reducing LDL cholesterol ( LDL-C ) . In animals , ezetimibe reversed diet-induced obesity , liver steatosis , and insulin resistance . In humans , its potential effects on liver steatosis and insulin resistance have been suggested . We investigated the effects of ezetimibe on postpr and ial hyperlipidaemia and hyperglycaemia in obese subjects with dyslipidaemia in a double-blind r and omized crossover trial . METHODS Twenty obese men with hypertriglyceridaemia were assigned r and omly to an ezetimibe- or a placebo-precedence-treated group . Subjects in the ezetimibe group were treated with ezetimibe ( 10 mg/day ) for the first 4 weeks , followed by a 4-week interval and then treated with placebo for another 4 weeks . The placebo group received these treatments in reverse order . Subjects were requested to fast for at least 12 hours and then received a st and ard meal . Blood sample s were collected at 0 , 30 , 60 , 120 , 240 , 360 and 480 minutes after the meal on Days 0 , 28 , 56 and 84 and were used to measure the lipid and glucose metabolism markers . RESULTS Ezetimibe significantly decreased the postpr and ial serum triglyceride excursion ( p=0.01 ) and fasting serum LDL-C , remnant-like particles(RLP ) and ApoB48 levels ( p<0.05 ) . Postpr and ial glucose excursion , serum insulin levels , serum glucose-dependent insulinotropic polypeptide ( GIP ) and active glucagon-like peptide-1 ( GLP-1 ) were not significantly affected by ezetimibe treatment . CONCLUSION Ezetimibe restored the postpr and ial dysregulation of lipid but did not affect glucose metabolism in a double-blind r and omized crossover trial OBJECTIVE To assess the effects of inhibited gastrointestinal cholesterol absorption in statin-treated dyslipidemic patients . RESEARCH DESIGN AND METHODS In a multicenter prospect i ve r and omized double-blind placebo-controlled trial , we primarily compared by ANCOVA the effect of 2-month ezetimibe ( 10 mg/day ) or placebo therapy on LDL cholesterol serum levels in 108 type 2 diabetic patients with albuminuria < 200 μg/min and total cholesterol concentrations > 135 mg/dl despite simvastatin treatment ( 40 mg/day ) . RESULTS Unlike placebo , ezetimibe  decreased LDL cholesterol from 99 ± 31 to 66 ± 22 mg/dl , total cholesterol from 162 ± 36 to 124 ± 30 mg/dl , and apolipoprotein B from 83 ± 22 to 64 ± 18 mg/dl ( P < 0.0001 for all changes versus placebo ) . A total of 72 and 17 % of patients on ezetimibe or placebo  achieved LDL levels < 70 mg/dl , respectively ( P < 0.0001 ) . Treatment was well tolerated . CONCLUSIONS Adding ezetimibe to simvastatin therapy helps to improve the pro-atherogenic lipoprotein profile in type 2 diabetic patients who fail to reach recommended lipid targets with statin therapy alone Background It has been demonstrated that statins can increase intestinal sterol absorption . Augments in phytosterolemia seems related to cardiovascular disease . Objective We examined the role of soluble fiber intake in endogenous cholesterol synthesis and in sterol absorption among subjects under highly effective lipid-lowering therapy . Design In an open label , r and omized , parallel- design study with blinded endpoints , subjects with primary hypercholesterolemia ( n = 116 ) were assigned to receive during 12 weeks , a daily dose of 25 g of fiber ( corresponding to 6 g of soluble fibers ) plus rosuvastatin 40 mg ( n = 28 ) , rosuvastatin 40 mg alone ( n = 30 ) , sinvastatin 40 mg plus ezetimibe 10 mg plus 25 g of fiber ( n = 28 ) , or sinvastatin 40 mg plus ezetimibe 10 mg ( n = 30 ) alone . Results The four assigned therapies produced similar changes in total cholesterol , LDL-cholesterol , and triglycerides ( p < 0.001 vs. baseline ) and did not change HDL-cholesterol . Fiber intake decreased plasma campesterol ( p < 0.001 vs. baseline ) , particularly among those patients receiving ezetimibe ( p < 0.05 vs. other groups ) , and β-sitosterol ( p = 0.03 vs. baseline ) , with a trend for lower levels in the group receiving fiber plus ezetimibe ( p = 0.07 ) . Treatment with rosuvastatin alone or combined with soluble fiber was associated with decreased levels of desmosterol ( p = 0.003 vs. other groups ) . Compared to non-fiber supplemented individuals , those treated with fibers had weight loss ( p = 0.04 ) , reduced body mass index ( p = 0.002 ) and blood glucose ( p = 0.047 ) . Conclusion Among subjects treated with highly effective lipid-lowering therapy , the intake of 25 g of fibers added favorable effects , mainly by reducing phytosterolemia . Additional benefits include improvement in blood glucose and anthropometric parameters Background Statins are used to treat hypercholesterolemia in patients with type 2 diabetes mellitus , but many of these patients fail to achieve the target LDL-C level . Recent reports have suggested that a synergistic effect can be obtained by concomitant administration of the cholesterol absorption inhibitor ezetimibe and a statin . However , in patients with type 2 diabetes who are already being treated with satins , it remains unclear whether it is more effective to add ezetimibe or to increase the statin dose . Therefore , this study was performed to examine the effects of these two regimens on LDL-C and lipoproteins . Methods The subjects were type 2 diabetic patients under treatment with rosuvastatin ( 2.5 mg daily ) , who had LDL-C levels ≥80 mg/dL. They were r and omly allocated to a group that received add-on therapy with ezetimibe at 10 mg/day ( combination group , n = 40 ) or an increase of the rosuvastatin dose to 5 mg/day ( dose escalation group , n = 39 ) . These two groups were compared at baseline and after 12 weeks of treatment . Results The percent change of LDL-C was −31 % in the combination group and −12 % in the dose escalation group . Both groups showed a significant decrease , but the decrease was greater in the combination group . In both groups , there was a significant decrease in the levels of small dense LDL-C , oxidized LDL and remnant-like lipoprotein cholesterol . For all of these parameters , the percent changes were greater in the combination group . Only the combination group showed a significant decrease of triglycerides . Multivariate analysis was performed to identify factors associated with reaching an LDL-C level < 80 mg/dL. As a result , add-on therapy with ezetimibe was extracted as a factor related to improvement of LDL-C. Conclusions Compared with increasing the dose of rosuvastatin , the combination of rosuvastatin and ezetimibe not only achieves quantitative but also qualitative improvement of serum lipid levels in type 2 diabetic patients , suggesting that this combination could suppress the progression of atherosclerosis . Trial registration Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Summary Aim We aim ed to compare the effects of fixed‐dose combinations of ezetimibe plus rosuvastatin to rosuvastatin alone in patients with primary hypercholesterolemia , including a subgroup analysis of patients with diabetes mellitus ( DM ) or metabolic syndrome ( MetS ) . Method This multicenter eight‐week r and omized double‐blind phase III study evaluated the safety and efficacy of fixed‐dose combinations of ezetimibe 10 mg plus rosuvastatin , compared with rosuvastatin alone in patients with primary hypercholesterolemia . Four hundred and seven patients with primary hypercholesterolemia who required lipid‐lowering treatment according to the ATP III guideline were r and omized to one of the following six treatments for 8 weeks : fixed‐dose combinations with ezetimibe 10 mg daily plus rosuvastatin ( 5 , 10 , or 20 mg daily ) or rosuvastatin alone ( 5 , 10 , or 20 mg daily ) . Results Fixed‐dose combination of ezetimibe plus rosuvastatin significantly reduced LDL cholesterol , total cholesterol , and triglyceride levels compared with rosuvastatin alone . Depending on the rosuvastatin dose , these fixed‐dose combinations of ezetimibe plus rosuvastatin  provided LDL cholesterol , total cholesterol , and triglyceride reductions of 56%–63 % , 37%–43 % , and 19%–24 % , respectively . Moreover , the effect of combination treatment on cholesterol levels was more pronounced in patients with DM or MetS than in non‐DM or non‐MetS patients , respectively , whereas the effect of rosuvastatin alone did not differ between DM vs non‐DM or MetS vs non‐MetS patients . Conclusion Fixed‐dose combinations of ezetimibe and rosuvastatin provided significantly superior efficacy  to rosuvastatin alone in lowering LDL cholesterol , total cholesterol , and triglyceride levels . Moreover , the reduction rate was greater in patients with DM or Objective . To investigate the effect of ezetimibe on the insulin secretion in db/db mice . Methods . The db/db diabetic mice aged 8 weeks were r and omly assigned into 2 groups and intragastrically treated 
    Output:
    