***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: AIMS To compare the efficacy and safety of once-daily pr and ial lixisenatide with placebo in type 2 diabetes mellitus ( T2DM ) insufficiently controlled by pioglitazone ± metformin . METHODS This r and omized , double-blind study included a 24-week main treatment period and a ≥52-week variable extension period . Patients were r and omized 2 : 1 to receive lixisenatide 20 µg once daily or placebo . The primary endpoint was change in glycated haemoglobin ( HbA1c ) at week 24 . RESULTS In total , 484 patients were r and omized : 323 to lixisenatide ; 161 to placebo . After 24 weeks , lixisenatide once daily significantly improved HbA1c ( -0.56 % vs. placebo ; p < 0.0001 ) and increased the proportion of patients achieving HbA1c < 7 % compared with placebo ( 52.3 % vs. 26.4 % , respectively ; p < 0.0001 ) and significantly improved fasting plasma glucose ( -0.84 mmol/l vs. placebo ; p < 0.0001 ) . There was a small decrease in body weight  with lixisenatide once daily and a small increase with placebo , with no statistically significant difference between the two groups . Overall , lixisenatide once daily was well tolerated , with a similar proportion of treatment-emergent adverse events ( TEAEs ) and serious TEAEs between groups ( lixisenatide : 72.4 % and 2.5 % ; placebo : 72.7 % and 1.9 % ) . Symptomatic hypoglycaemia rates were also relatively low in both groups ( lixisenatide 3.4 % and placebo 1.2 % ) , with no severe episodes . Lixisenatide continued to be efficacious and well tolerated during the variable extension period . CONCLUSIONS Lixisenatide once daily significantly improved glycaemic control with a low risk of hypoglycaemia , and was well tolerated over 24 weeks and during the long-term , double-blind extension period in patients with T2DM insufficiently controlled on pioglitazone ± metformin OBJECTIVE To examine the efficacy and safety of lixisenatide ( 20 μg once daily , administered before the morning or evening meal ) as add-on therapy in patients with type 2 diabetes insufficiently controlled with metformin alone . RESEARCH DESIGN AND METHODS This was a 24-week , r and omized , double-blind , placebo-controlled study in 680 patients with inadequately controlled type 2 diabetes ( HbA1c 7–10 % [ 53−86 mmol/mol ] ) . Patients were r and omized to lixisenatide morning ( n = 255 ) , lixisenatide evening ( n = 255 ) , placebo morning ( n = 85 ) , or placebo evening ( n = 85 ) injections . RESULTS Lixisenatide morning injection significantly reduced mean HbA1c versus combined placebo ( mean change −0.9 % [ 9.8 mmol/mol ] vs. −0.4 % [ 4.4 mmol/mol ] ; least squares [ LS ] mean difference vs. placebo −0.5 % [ 5.5 mmol/mol ] , P < 0.0001 ) . HbA1c was significantly reduced by lixisenatide evening injection ( mean change –0.8 % [ 8.7 mmol/mol ] vs. –0.4 % [ 4.4 mmol/mol ] ; LS mean difference –0.4 % [ 4.4 mmol/mol ] , P < 0.0001 ) . Lixisenatide morning injection significantly reduced 2-h postpr and ial glucose versus morning placebo ( mean change −5.9 vs. −1.4 mmol/L ; LS mean difference −4.5 mmol/L , P < 0.0001 ) . LS mean difference in fasting plasma glucose was significant in both morning ( –0.9 mmol/L , P < 0.0001 ) and evening ( –0.6 mmol/L , P = 0.0046 ) groups versus placebo . Mean body weight decreased to a similar extent in all groups . Rates of adverse events were 69.4 % in both lixisenatide groups and 60.0 % in the  placebo group . Rates for nausea and vomiting were 22.7 and 9.4 % for lixisenatide morning and 21.2 and 13.3 % for lixisenatide evening versus 7.6 and 2.9 % for placebo , respectively . Symptomatic hypoglycemia occurred in 6 , 13 , and 1 patient for lixisenatide morning , evening , and placebo , respectively , with no severe episodes . CONCLUSIONS In patients with type 2 diabetes inadequately controlled on metformin  , lixisenatide 20 μg once daily administered in the morning or evening significantly improved glycemic control , with a pronounced postpr and ial effect , and was well tolerated Aim Assess the pharmacodynamics of lixisenatide once daily ( QD ) versus liraglutide QD in type 2 diabetes insufficiently controlled on metformin . Methods In this 28-day , r and omized , open-label , parallel-group , multicentre study ( NCT01175473 ) , patients ( mean HbA1c 7.3 % ) received subcutaneous lixisenatide QD  ( 10 µg weeks 1–2 , then 20 µg ; n = 77 ) or liraglutide QD ( 0.6 mg week 1 , 1.2 mg week 2 , then 1.8 mg ; n = 71 ) 30 min before breakfast . Primary endpoint was change in postpr and ial plasma glucose ( PPG ) exposure from baseline to day 28 during a breakfast test meal . Results Lixisenatide  reduced PPG significantly more than liraglutide [ mean change in AUC0:30–4:30h : −12.6 vs. −4.0 h·mmol/L , respectively ; p < 0.0001 ( 0:30 h = start of meal ) ] . Change in maximum PPG excursion was −3.9 mmol/l vs. −1.4 mmol/l , respectively ( p < 0.0001 ) . More lixisenatide-treated patients achieved 2-h PPG < 7.8 mmol/l ( 69 % vs. 29 % ) . Changes in fasting plasma glucose were greater with liraglutide ( −0.3 vs. −1.3 mmol/l , p < 0.0001  ) . Lixisenatide provided greater decreases in postpr and ial glucagon ( p < 0.05 ) , insulin ( p < 0.0001 ) and C-peptide ( p < 0.0001 ) . Mean HbA1c decreased in both treatment groups ( from 7.2 % to 6.9 % with lixisenatide vs. 7.4 % to 6.9 % with liraglutide ) as did body weight ( −1.6 kg vs. −2.4 kg , respectively ) . Overall incidence of adverse events was lower with lixisenatide ( 55 % ) versus liraglutide ( 65 % ) , with no serious events or hypoglycaemia reported . Conclusions Once daily prebreakfast lixisenatide provided a significantly greater reduction in PPG ( AUC ) during a morning test meal versus prebreakfast liraglutide . Lixisenatide provided significant decreases in postpr and ial insulin , C-peptide ( vs. an increase with liraglutide ) and glucagon , and better gastrointestinal tolerability than liraglutide AIMS To evaluate the effects of liraglutide after 14 weeks of treatment on serum adipokines , insulin resistance index and cardiovascular risk biomarkers in overweight or obese T2DM patients unable to achieve glycemic control with metformin alone or in association with a sulfonylurea in daily clinical practice . METHODS Prospect i ve study in 59 consecutive overweight or obese ( BMI ≥25kg/m(2 ) ) T2DM patients unable to achieve glycemic control ( HbA1c>7 % , 53mmol/mol ) with metformin alone or in association with sulfonylurea that require initiation of liraglutide in progressive dose increase up to 1.8mg/day subcutaneously . Weight , body composition , blood pressure , glucose , HbA1c , C-peptide , insulin , plasma lipids , adipokines ( leptin , adiponectin , resistin and visfatin ) as well as cardiovascular biomarkers ( IL-6 and TNF-a ) levels were measured fasting at baseline and 14 weeks after liraglutide initiation . RESULTS 14 weeks of liraglutide treatment significantly reduced HbA1c , BMI and total body fat mass by 0.9 % , 1.4kg/m(2 ) and 0.5 % respectively . Statistically significant lower insulin resistance and higher insulin secretion was found by HOMA-IR 8.4 ( 1.6 ) vs 4.6 (0.9)molmIU/L(2 ) and HOMA-B 48.2 ( 9.0 ) vs 87.6 (16.3)μIU/mmol . Statistically significantly higher levels of visfatin 6.3 ( 2.1 ) vs 6.8 (2.1)ng/ml and resistin 3.6 ( 2.0 ) vs 4.3 (2.3)ng/ml were also observed after treatment . Baseline visfatin was negatively correlated with basal fasting plasma glucose r=-0.360 ( p<0.05 ) . CONCLUSIONS Liraglutide treatment for 14 weeks in daily clinical practice led to reduction of BMI and improvement of glucose control and insulin sensitivity and resistance parameters . Additionally , circulating levels of adipokines and pro-inflammatory factors could play an important role in GLP-1 treatment response Despite the increasing prevalence of nonalcoholic fatty liver disease ( NAFLD ) , the criteria used to diagnose the disorder remain poorly defined . Localized proton magnetic resonance spectroscopy ( MRS ) accurately measures hepatic triglyceride content ( HTGC ) but has been used only in small research studies . Here , MRS was used to analyze the distribution of HTGC in 2,349 participants from the Dallas Heart Study ( DHS ) . The reproducibility of the procedure was vali date d by showing that duplicate HTGC measurements were high correlated ( r = 0.99 , P < 0.001 ) and that the coefficient of variation between measurements was low ( 8.5 % ) . Intake of a high-fat meal did not significantly affect the measurements , and values were similar when measurements were made from the right and left hepatic lobes . To determine the " upper limit of normal " for HTGC , the distribution of HTGC was examined in the 345 subjects from the DHS who had no identifiable risk factors for hepatic steatosis ( nonobese , nondiabetic subjects with minimal alcohol consumption , normal liver function tests , and no known liver disease ) . The 95th percentile of HTGC in these subjects was 5.56 % , which corresponds to a hepatic triglyceride level of 55.6 mg/g . With this value as a cutoff , the prevalence of hepatic steatosis in Dallas County was estimated to be 33.6 % . Thus MRS provides a sensitive , quantitative , noninvasive method to measure HTGC and , when applied to a large urban US population , revealed a strikingly high prevalence of hepatic steatosis OBJECTIVE When oral therapy for type 2 diabetes is ineffective , adding basal insulin improves glycemic control . However , when glycated hemoglobin ( HbA1c ) remains elevated because of postpr and ial hyperglycemia , the next therapeutic step is controversial . We examined the efficacy and safety of  lixisenatide  in patients with HbA1c still elevated after initiation of insulin glargine . RESEARCH DESIGN AND METHODS This double-blind , parallel-group trial enrolled patients with HbA1c 7–10 % despite oral therapy .  Insulin glargine was added and systematic ally titrated during a 12-week run-in , after which c and i date s with fasting glucose ≤7.8 mmol/L and HbA1c 7–9 % were r and omized  to lixisenatide 20 µg or placebo for 24 weeks while insulin titration continued . The primary end point was HbA1c change after r and omization . RESULTS The r and omized population ( n = 446 ) had mean diabetes duration of 9.2 years , BMI 31.8 kg/m2 , and daily glargine dosage of 44 units . HbA1c had decreased during run-in from 8.6 to 7.6 % ; adding lixisenatide further reduced HbA1c by 0.71 vs. 0.40 % with placebo ( least squares mean difference , –0.32 % ; 95 % CI , –0.46 to –0.17 ; P < 0.0001 ) . More participants  attained HbA1c < 7  % with lixisenatide ( 56 vs. 39 % ; P < 
    Output:
    
No effects of lixisenatide were identified on AST , alkaline phosphatase or bilirubin .
No evidence of bias was identified .
Mixed effect multilevel meta-regression analyses suggest that the benefit of lixisenatide on ALT was limited to patients who were overweight or obese .
This review suggests that lixisenatide increases the proportion of obese or overweight patients with type 2 diabetes who achieve normalisation of ALT .