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: BACKGROUND Previous studies demonstrated that in experimental animals fatty liver is associated with reduced hepatic blood flow and that metformin reverses steatosis , while no data were reported in humans . AIMS To evaluate the clinical relevance of echo-Doppler measurements and the effects of therapy in non-alcoholic fatty liver disease . PATIENTS Twenty patients with biopsy proven non-alcoholic fatty liver disease . METHODS Abdominal echo-Doppler examination was performed at enrolment and , in 11 patients , after 6 months of dietary/pharmacological therapy ( metformin 500 mg three times a day ) . RESULTS Non-alcoholic fatty liver disease was characterised by hepatomegaly , bright echotexture and posterior attenuation . Mean portal blood velocity and flow were low-normal . Brightness and posterior attenuation significantly correlated with fat score in liver biopsies as well as with the hepatic veins spectrum . After therapy , echotexture improved and liver volume significantly decreased . Portal blood velocity and flow significantly increased , intrahepatic arterial indexes decreased and the spectrum of hepatic veins improved . CONCLUSIONS Fatty liver is associated with an impaired hepatic blood flow characterised by increased intrahepatic resistances . Vascular changes are reversed by treatment and can be measured by echo-Doppler which may be useful to evaluate the natural course of non-alcoholic fatty liver disease , and to monitor the putative beneficial effects of therapy OBJECTIVE This study determined the effects of insulin versus liraglutide therapy on liver fat in patients with type 2 diabetes inadequately controlled with oral agents therapy , including metformin . RESEARCH DESIGN AND METHODS Thirty-five patients with type 2 diabetes inadequately controlled on metformin monotherapy or in combination with other oral antidiabetic medications  were r and omized to receive insulin glargine or liraglutide therapy for 12 weeks . The liver proton density fat fraction ( PDFF ) was measured by MRS . The mean liver PDFF , the total liver volume , and the total liver fat index were measured by MRI . The Student t test , the Fisher exact test , and repeated- measures ANOVA were used for statistical analysis . RESULTS Insulin treatment was associated with a significant improvement in glycated hemoglobin ( 7.9 % to 7.2 % [ 62.5 to 55.2 mmol/mol ] , P = 0.005 ) , a trend toward a decrease in MRS-PDFF ( 12.6 % to 9.9 % , P = 0.06 ) , and a significant decrease in liver mean MRI-PDFF ( 13.8 % to 10.6 % , P = 0.005 ) , liver volume ( 2,010.6 to 1,858.7 mL , P = 0.01 ) , and the total liver fat index ( 304.4 vs. 209.3 % ⋅ mL , P = 0.01 ) . Liraglutide treatment was also associated with a significant improvement in glycated hemoglobin ( 7.6 % to 6.7 % [ 59.8 to 50.2 mmol/mol ] , P < 0.001 ) but did not change MRS-PDFF ( P = 0.80 ) , liver mean MRI-PDFF ( P = 0.15 ) , liver volume ( P = 0.30 ) , or the total liver fat index ( P = 0.39 ) . CONCLUSIONS The administration of insulin glargine therapy reduced the liver fat burden in patients with type 2 diabetes . However , the improvements in the liver fat fraction and glycemia control were not significantly different from those in the liraglutide group Tirasemtiv is a fast skeletal troponin activator that sensitizes the sarcomere to calcium and increases muscle force following subtetanic nerve input . In an animal model of myasthenia gravis ( MG ) , single oral doses of tirasemtiv improved muscle force and reduced fatigability . The purpose of this study was to determine the effect of single doses of tirasemtiv on skeletal muscle function and fatigability in patients with generalized MG . Thirty-two patients with acetylcholine receptor-antibody positive MG and muscle weakness received single doses of tirasemtiv ( 250 mg or 500 mg ) or placebo in a double-blind , r and omized treatment sequence with each treatment separated by at least 1 week . Outcome measures included the Quantitative MG Score ( QMG ) , MG Composite , Manual Muscle Testing , and forced vital capacity . At 6 h after dosing , tirasemtiv produced dose-related improvements from baseline in the QMG score ( slope : –0.49 QMG point per 250 mg ; p = 0.02 ) and in percent predicted forced vital capacity ( slope : 2.2 % per 250 mg ; p = 0.04 ) . QMG improved > 3 points in twice as many patients after 500 mg tirasemtiv than after placebo . Both doses of tirasemtiv were well tolerated ; there were no premature terminations or serious adverse events . The results of this study suggest that tirasemtiv may improve muscle function in MG and will be used to support further development of tirasemtiv in neuromuscular diseases BACKGROUND Exenatide , an incretin mimetic for adjunctive treatment of type 2 diabetes ( T2DM ) , reduced hemoglobin A(1c ) ( A1C ) and weight in clinical trials . The objective of this study was to evaluate the effects of > or = 3 years exenatide therapy on glycemic control , body weight , cardiometabolic markers , and safety . METHODS Patients from three placebo-controlled trials and their open-label extensions were enrolled into one open-ended , open-label clinical trial . Patients were r and omized to twice daily ( BID ) placebo , 5 mug exenatide , or 10 mug exenatide for 30 weeks , followed by 5 mug exenatide BID for 4 weeks , then 10 mug exenatide BID for > or = 3 years of exenatide exposure . Patients continued metformin and /or sulfonylureas . RESULTS 217 patients ( 64 % male , age 58 + /- 10 years , weight 99 + /- 18 kg , BMI 34 + /- 5 kg/m(2 ) , A1C 8.2 + /- 1.0 % [ mean + /- SD ] ) completed 3 years of exenatide exposure . Reductions in A1C from baseline to week 12 ( -1.1 + /- 0.1 % [ mean + /- SEM ] ) were sustained to 3 years ( -1.0 + /- 0.1 % ; p < 0.0001 ) , with 46 % achieving A1C < or = 7 % . Exenatide progressively reduced body weight from baseline ( -5.3 + /- 0.4 kg at 3 years ; p < 0.0001 ) . Patients with elevated serum alanine aminotransferase ( ALT ) at baseline ( n = 116 ) had reduced ALT ( -10.4 + /- 1.5 IU/L ; p < 0.0001 ) and 41 % achieved normal ALT . Patients with elevated ALT at baseline tended to lose more weight than patients with normal ALT at baseline ( -6.1 + /- 0.6 kg vs. -4.4 + /- 0.5 kg ; p = 0.03 ) , however weight change was minimally correlated with baseline ALT ( r = -0.01 ) or ALT change ( r = 0.31 ) . Homeostasis Model Assessment B ( HOMA-B ) , blood pressure , and aspartate aminotransferase ( AST ) all improved . A subset achieved 3.5 years of exenatide exposure and had serum lipids available for analysis ( n = 151 ) .  Triglycerides decreased 12 % ( p = 0.0003 ) , total cholesterol decreased 5 % ( p = 0.0007 ) , LDL-C decreased 6 % ( p < 0.0001 ) , and HDL-C increased 24 % ( p < 0.0001 ) . Exenatide was generally well tolerated . The most frequent adverse event was mild-to-moderate nausea . The main limitation of this study is the open-label , uncontrolled nature of the study design which does not provide a placebo group for comparison . CONCLUSION Adjunctive exenatide treatment for > or = 3 years in T2DM patients result ed in sustained improvements in glycemic control , cardiovascular risk factors , and hepatic biomarkers , coupled with progressive weight reduction AIM We evaluated the efficacy and safety of ertugliflozin , an SGLT2 inhibitor , in type 2 diabetes mellitus ( T2DM ) inadequately controlled ( HbA1c , 7.0%-10.5 % ) with metformin monotherapy ( ≥1500 mg/d for ≥8 weeks ) . METHODS This was a double-blind , 26-week , multicentre study with ongoing 78-week extension ( Clinical Trials.gov identifier : NCT02033889 ) . A total of 621 participants were r and omized 1:1:1 to placebo , or ertugliflozin 5 or 15 mg/d . The primary endpoint was change from baseline at week 26 in HbA1c . Secondary efficacy endpoints were change from baseline at week 26 in fasting plasma glucose ( FPG ) , body weight , systolic/diastolic blood pressure ( SBP/DBP ) and number of participants with HbA1c < 7.0 % ( 53 mmol/mol ) . Pre-specified adverse events ( AEs ) of special interest and percent change from baseline in bone mineral density ( BMD ) were also assessed at week 26 . RESULTS At week 26 , the placebo-adjusted least-squares mean change from baseline HbA1c ( 8.1 % ) was -0.7 % and -0.9 % for ertugliflozin 5 and 15 mg , respectively ( both P < .001 ) , to final means of 7.3 % and 7.2 % , respectively . The odds of HbA1c < 7.0 % were significantly greater in both ertugliflozin groups vs placebo . Ertugliflozin significantly reduced FPG , body weight , SBP and DBP vs placebo . The incidence of genital mycotic infections was higher in the ertugliflozin groups ( female subjects : placebo , 0.9 % ; ertugliflozin 5 mg , 5.5 % ; ertugliflozin 15 mg , 6.3 % [ P = .032 ] ; male subjects : 0 % ; 3.1 % ; 3.2 % , respectively ) , as was the incidence of urinary tract infections and symptomatic hypoglycaemia . The incidence of hypovolaemia AEs was similar across  groups . Ertugliflozin had no adverse impact on BMD at week 26 . CONCLUSIONS Ertugliflozin added to metformin in patients with inadequately controlled T2DM improved glycaemic control , reduced body weight and BP , but increased the incidence of genital mycotic infections Background : Nonalcoholic fatty liver disease is very frequent in type 2 diabetes , with increased risk of further development of liver fibrosis . Animal studies have shown that GLP-1 receptor agonists may reduce liver lipogenesis . However , data in humans are scarce . Objective : To study the effect of liraglutide 1.2 mg/d on liver fat content ( LFC ) in patients with uncontrolled type 2 diabetes and to evaluate the factors potentially associated with liraglutide-induced modification of LFC . Design , Setting , Participants : LFC was measured by proton magnetic resonance spectroscopy before and after 6 months of liraglutide treatment in 68 patients with uncontrolled type 2 diabetes mellitus . Intervention : Liraglutide 1.2 mg/d . Outcome measure : Change in LFC . Results : Treatment with liraglutide was associated with a significant decrease in body weight , HbA1C , and a marked relative reduction in LFC of 31 % ( P < 0.0001 ) . No significant modification of LFC was observed in a parallel group of patients 6 months after intensification of the antidiabetic treatment with insulin . The reduction in LFC and body weight were highly correlated ( r = 0.490 ; P < 0.0001 ) . In multivariate analysis , the reduction in LFC was independently associated with baseline LFC ( P < 0.0001 ) , age ( P = 0.010 ) , and reduction in body weight ( P < 0.0001 ) , triglycerides ( P = 0.019 ) , and HbA1c ( P = 0.034 ) . In the patients who had no significant decrease in body weight , no significant reduction in LFC was observed . Conclusions : Six months of treatment with liraglutide 1.2 mg/d significantly reduced LFC  in patients with inadequately controlled type 2 diabetes and this effect was mainly driven by body weight reduction . Further studies are needed to confirm that this reduction in LFC may significantly reduce fibrosis pro 
    Output:
    
agent
***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: BACKGROUND Previous studies demonstrated that in experimental animals fatty liver is associated with reduced hepatic blood flow and that metformin reverses steatosis , while no data were reported in humans . AIMS To evaluate the clinical relevance of echo-Doppler measurements and the effects of therapy in non-alcoholic fatty liver disease . PATIENTS Twenty patients with biopsy proven non-alcoholic fatty liver disease . METHODS Abdominal echo-Doppler examination was performed at enrolment and , in 11 patients , after 6 months of dietary/pharmacological therapy ( metformin 500 mg three times a day ) . RESULTS Non-alcoholic fatty liver disease was characterised by hepatomegaly , bright echotexture and posterior attenuation . Mean portal blood velocity and flow were low-normal . Brightness and posterior attenuation significantly correlated with fat score in liver biopsies as well as with the hepatic veins spectrum . After therapy , echotexture improved and liver volume significantly decreased . Portal blood velocity and flow significantly increased , intrahepatic arterial indexes decreased and the spectrum of hepatic veins improved . CONCLUSIONS Fatty liver is associated with an impaired hepatic blood flow characterised by increased intrahepatic resistances . Vascular changes are reversed by treatment and can be measured by echo-Doppler which may be useful to evaluate the natural course of non-alcoholic fatty liver disease , and to monitor the putative beneficial effects of therapy OBJECTIVE This study determined the effects of insulin versus liraglutide therapy on liver fat in patients with type 2 diabetes inadequately controlled with oral agents therapy , including metformin . RESEARCH DESIGN AND METHODS Thirty-five patients with type 2 diabetes inadequately controlled on metformin monotherapy or in combination with other oral antidiabetic medications  were r and omized to receive insulin glargine or liraglutide therapy for 12 weeks . The liver proton density fat fraction ( PDFF ) was measured by MRS . The mean liver PDFF , the total liver volume , and the total liver fat index were measured by MRI . The Student t test , the Fisher exact test , and repeated- measures ANOVA were used for statistical analysis . RESULTS Insulin treatment was associated with a significant improvement in glycated hemoglobin ( 7.9 % to 7.2 % [ 62.5 to 55.2 mmol/mol ] , P = 0.005 ) , a trend toward a decrease in MRS-PDFF ( 12.6 % to 9.9 % , P = 0.06 ) , and a significant decrease in liver mean MRI-PDFF ( 13.8 % to 10.6 % , P = 0.005 ) , liver volume ( 2,010.6 to 1,858.7 mL , P = 0.01 ) , and the total liver fat index ( 304.4 vs. 209.3 % ⋅ mL , P = 0.01 ) . Liraglutide treatment was also associated with a significant improvement in glycated hemoglobin ( 7.6 % to 6.7 % [ 59.8 to 50.2 mmol/mol ] , P < 0.001 ) but did not change MRS-PDFF ( P = 0.80 ) , liver mean MRI-PDFF ( P = 0.15 ) , liver volume ( P = 0.30 ) , or the total liver fat index ( P = 0.39 ) . CONCLUSIONS The administration of insulin glargine therapy reduced the liver fat burden in patients with type 2 diabetes . However , the improvements in the liver fat fraction and glycemia control were not significantly different from those in the liraglutide group Tirasemtiv is a fast skeletal troponin activator that sensitizes the sarcomere to calcium and increases muscle force following subtetanic nerve input . In an animal model of myasthenia gravis ( MG ) , single oral doses of tirasemtiv improved muscle force and reduced fatigability . The purpose of this study was to determine the effect of single doses of tirasemtiv on skeletal muscle function and fatigability in patients with generalized MG . Thirty-two patients with acetylcholine receptor-antibody positive MG and muscle weakness received single doses of tirasemtiv ( 250 mg or 500 mg ) or placebo in a double-blind , r and omized treatment sequence with each treatment separated by at least 1 week . Outcome measures included the Quantitative MG Score ( QMG ) , MG Composite , Manual Muscle Testing , and forced vital capacity . At 6 h after dosing , tirasemtiv produced dose-related improvements from baseline in the QMG score ( slope : –0.49 QMG point per 250 mg ; p = 0.02 ) and in percent predicted forced vital capacity ( slope : 2.2 % per 250 mg ; p = 0.04 ) . QMG improved > 3 points in twice as many patients after 500 mg tirasemtiv than after placebo . Both doses of tirasemtiv were well tolerated ; there were no premature terminations or serious adverse events . The results of this study suggest that tirasemtiv may improve muscle function in MG and will be used to support further development of tirasemtiv in neuromuscular diseases BACKGROUND Exenatide , an incretin mimetic for adjunctive treatment of type 2 diabetes ( T2DM ) , reduced hemoglobin A(1c ) ( A1C ) and weight in clinical trials . The objective of this study was to evaluate the effects of > or = 3 years exenatide therapy on glycemic control , body weight , cardiometabolic markers , and safety . METHODS Patients from three placebo-controlled trials and their open-label extensions were enrolled into one open-ended , open-label clinical trial . Patients were r and omized to twice daily ( BID ) placebo , 5 mug exenatide , or 10 mug exenatide for 30 weeks , followed by 5 mug exenatide BID for 4 weeks , then 10 mug exenatide BID for > or = 3 years of exenatide exposure . Patients continued metformin and /or sulfonylureas . RESULTS 217 patients ( 64 % male , age 58 + /- 10 years , weight 99 + /- 18 kg , BMI 34 + /- 5 kg/m(2 ) , A1C 8.2 + /- 1.0 % [ mean + /- SD ] ) completed 3 years of exenatide exposure . Reductions in A1C from baseline to week 12 ( -1.1 + /- 0.1 % [ mean + /- SEM ] ) were sustained to 3 years ( -1.0 + /- 0.1 % ; p < 0.0001 ) , with 46 % achieving A1C < or = 7 % . Exenatide progressively reduced body weight from baseline ( -5.3 + /- 0.4 kg at 3 years ; p < 0.0001 ) . Patients with elevated serum alanine aminotransferase ( ALT ) at baseline ( n = 116 ) had reduced ALT ( -10.4 + /- 1.5 IU/L ; p < 0.0001 ) and 41 % achieved normal ALT . Patients with elevated ALT at baseline tended to lose more weight than patients with normal ALT at baseline ( -6.1 + /- 0.6 kg vs. -4.4 + /- 0.5 kg ; p = 0.03 ) , however weight change was minimally correlated with baseline ALT ( r = -0.01 ) or ALT change ( r = 0.31 ) . Homeostasis Model Assessment B ( HOMA-B ) , blood pressure , and aspartate aminotransferase ( AST ) all improved . A subset achieved 3.5 years of exenatide exposure and had serum lipids available for analysis ( n = 151 ) .  Triglycerides decreased 12 % ( p = 0.0003 ) , total cholesterol decreased 5 % ( p = 0.0007 ) , LDL-C decreased 6 % ( p < 0.0001 ) , and HDL-C increased 24 % ( p < 0.0001 ) . Exenatide was generally well tolerated . The most frequent adverse event was mild-to-moderate nausea . The main limitation of this study is the open-label , uncontrolled nature of the study design which does not provide a placebo group for comparison . CONCLUSION Adjunctive exenatide treatment for > or = 3 years in T2DM patients result ed in sustained improvements in glycemic control , cardiovascular risk factors , and hepatic biomarkers , coupled with progressive weight reduction AIM We evaluated the efficacy and safety of ertugliflozin , an SGLT2 inhibitor , in type 2 diabetes mellitus ( T2DM ) inadequately controlled ( HbA1c , 7.0%-10.5 % ) with metformin monotherapy ( ≥1500 mg/d for ≥8 weeks ) . METHODS This was a double-blind , 26-week , multicentre study with ongoing 78-week extension ( Clinical Trials.gov identifier : NCT02033889 ) . A total of 621 participants were r and omized 1:1:1 to placebo , or ertugliflozin 5 or 15 mg/d . The primary endpoint was change from baseline at week 26 in HbA1c . Secondary efficacy endpoints were change from baseline at week 26 in fasting plasma glucose ( FPG ) , body weight , systolic/diastolic blood pressure ( SBP/DBP ) and number of participants with HbA1c < 7.0 % ( 53 mmol/mol ) . Pre-specified adverse events ( AEs ) of special interest and percent change from baseline in bone mineral density ( BMD ) were also assessed at week 26 . RESULTS At week 26 , the placebo-adjusted least-squares mean change from baseline HbA1c ( 8.1 % ) was -0.7 % and -0.9 % for ertugliflozin 5 and 15 mg , respectively ( both P < .001 ) , to final means of 7.3 % and 7.2 % , respectively . The odds of HbA1c < 7.0 % were significantly greater in both ertugliflozin groups vs placebo . Ertugliflozin significantly reduced FPG , body weight , SBP and DBP vs placebo . The incidence of genital mycotic infections was higher in the ertugliflozin groups ( female subjects : placebo , 0.9 % ; ertugliflozin 5 mg , 5.5 % ; ertugliflozin 15 mg , 6.3 % [ P = .032 ] ; male subjects : 0 % ; 3.1 % ; 3.2 % , respectively ) , as was the incidence of urinary tract infections and symptomatic hypoglycaemia . The incidence of hypovolaemia AEs was similar across  groups . Ertugliflozin had no adverse impact on BMD at week 26 . CONCLUSIONS Ertugliflozin added to metformin in patients with inadequately controlled T2DM improved glycaemic control , reduced body weight and BP , but increased the incidence of genital mycotic infections Background : Nonalcoholic fatty liver disease is very frequent in type 2 diabetes , with increased risk of further development of liver fibrosis . Animal studies have shown that GLP-1 receptor agonists may reduce liver lipogenesis . However , data in humans are scarce . Objective : To study the effect of liraglutide 1.2 mg/d on liver fat content ( LFC ) in patients with uncontrolled type 2 diabetes and to evaluate the factors potentially associated with liraglutide-induced modification of LFC . Design , Setting , Participants : LFC was measured by proton magnetic resonance spectroscopy before and after 6 months of liraglutide treatment in 68 patients with uncontrolled type 2 diabetes mellitus . Intervention : Liraglutide 1.2 mg/d . Outcome measure : Change in LFC . Results : Treatment with liraglutide was associated with a significant decrease in body weight , HbA1C , and a marked relative reduction in LFC of 31 % ( P < 0.0001 ) . No significant modification of LFC was observed in a parallel group of patients 6 months after intensification of the antidiabetic treatment with insulin . The reduction in LFC and body weight were highly correlated ( r = 0.490 ; P < 0.0001 ) . In multivariate analysis , the reduction in LFC was independently associated with baseline LFC ( P < 0.0001 ) , age ( P = 0.010 ) , and reduction in body weight ( P < 0.0001 ) , triglycerides ( P = 0.019 ) , and HbA1c ( P = 0.034 ) . In the patients who had no significant decrease in body weight , no significant reduction in LFC was observed . Conclusions : Six months of treatment with liraglutide 1.2 mg/d significantly reduced LFC  in patients with inadequately controlled type 2 diabetes and this effect was mainly driven by body weight reduction . Further studies are needed to confirm that this reduction in LFC may significantly reduce fibrosis pro 
    Output:
    