***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 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 OBJECTIVE To assess the effects of exenatide on body weight and glucose tolerance in nondiabetic obese subjects with normal or impaired glucose tolerance ( IGT ) or impaired fasting glucose ( IFG ) . RESEARCH DESIGN AND METHODS Obese subjects ( n = 152 ; age 46 ± 12 years , female 82 % , weight 108.6 ± 23.0 kg , BMI 39.6 ± 7.0 kg/m2 , IGT or IFG 25 % ) were r and omized to receive exenatide ( n = 73 ) or placebo ( n = 79 ) , along with lifestyle intervention , for 24 weeks . RESULTS Exenatide-treated subjects lost 5.1 ± 0.5 kg from baseline versus 1.6 ± 0.5 kg with placebo ( exenatide − placebo , P < 0.001 ) . Placebo-subtracted difference in percent weight reduction was −3.3 ± 0.5 % ( P < 0.001 ) . Both groups reduced their daily calorie intake  ( exenatide , −449 cal ; placebo , −387 cal ) . IGT or IFG normalized at end point in 77 and 56 % of exenatide and placebo subjects , respectively . CONCLUSIONS Exenatide plus lifestyle modification decreased caloric intake and result ed in weight loss in nondiabetic obesity with improved glucose tolerance in subjects with IGT and IFG OBJECTIVE The aim was to evaluate the ability of liraglutide to augment weight loss and improve insulin resistance , cardiovascular disease ( CVD ) risk factors , and inflammation in a high-risk population for type 2 diabetes ( T2DM ) and CVD . RESEARCH DESIGN AND METHODS We r and omized 68 older individuals ( mean age , 58 ± 8 years ) with overweight/obesity and prediabetes to this double-blind study of liraglutide 1.8 mg versus placebo for 14 weeks . All subjects were advised to decrease calorie intake by 500 kcal/day . Peripheral insulin resistance was quantified by measuring the steady-state plasma glucose ( SSPG ) concentration during the insulin suppression test . Traditional CVD risk factors and inflammatory markers also were assessed . RESULTS Eleven out of 35 individuals ( 31 % ) assigned to liraglutide discontinued the study compared with 6 out of 33 ( 18 % ) assigned to placebo ( P = 0.26 ) . Subjects who continued to use liraglutide ( n = 24 ) lost twice as much weight as those using placebo ( n = 27 ; 6.8 vs. 3.3 kg ; P < 0.001 ) . Liraglutide-treated subjects also had a significant improvement in SSPG concentration ( −3.2 vs. 0.2 mmol/L ; P < 0.001 ) and significantly ( P ≤ 0.04 ) greater lowering of systolic blood pressure ( −8.1 vs. −2.6 mmHg ) , fasting glucose ( −0.5 vs. 0 mmol/L ) , and triglyceride ( −0.4 vs. −0.1 mmol/L ) concentration . Inflammatory markers did not differ between the two groups , but pulse increased after liraglutide treatment ( 6.4 vs. −0.9 bpm ; P = 0.001 ) . CONCLUSIONS The addition of liraglutide to calorie restriction significantly augmented weight loss and improved insulin resistance , systolic blood pressure , glucose , and triglyceride concentration in this population at high risk for development of T2DM and CVD Objective : Having demonstrated short-term weight loss with liraglutide in this group of obese adults , we now evaluate safety/tolerability ( primary outcome ) and long-term efficacy for sustaining weight loss ( secondary outcome ) over 2 years . Design : A r and omized , double-blind , placebo-controlled 20-week study with 2-year extension ( sponsor unblinded at 20 weeks , participants /investigators at 1 year ) in 19 European clinical research centers . Subjects : A total of 564 adults ( n=90–98 per group ; body mass index 30–40 kg m−2 ) enrolled , 398 entered the extension and 268 completed the 2-year trial . Participants received diet ( 500 kcal deficit per day ) and exercise counseling during 2-week run-in , before being r and omly assigned ( with a telephone or web-based system ) to once-daily subcutaneous liraglutide ( 1.2 , 1.8 , 2.4 or 3.0 mg , n=90–95 ) , placebo ( n=98 ) or open-label orlistat ( 120 mg × 3 , n=95 ) . After 1 year , liraglutide/placebo recipients switched to liraglutide 2.4 mg , then 3.0 mg ( based on 20-week and 1-year results , respectively ) . The trial ran from January 2007–April 2009 and is registered with Clinical trials.gov , number NCT00480909 . Results : From r and omization to year 1 , liraglutide 3.0 mg recipients lost 5.8 kg ( 95 % confidence interval 3.7–8.0 ) more weight than those on placebo and 3.8 kg ( 1.6–6.0 ) more than those on orlistat ( P⩽0.0001 ; intention-to-treat , last-observation-carried-forward ) . At year 2 , participants on liraglutide 2.4/3.0 mg for the full 2 years ( pooled group , n=184 ) lost 3.0 kg ( 1.3–4.7 ) more weight than those on orlistat ( n=95 ; P<0.001 ) . Completers on liraglutide 2.4/3.0 mg ( n=92 ) maintained a 2-year weight loss of 7.8 kg from screening . With liraglutide 3.0 mg , 20-week body fat decreased by 15.4 % and lean tissue by 2.0 % . The most frequent drug-related side effects were mild to moderate , transient nausea and vomiting . With liraglutide 2.4/3.0 mg , the 2-year prevalence of prediabetes and metabolic syndrome decreased by 52 and 59 % , with improvements in blood pressure and lipids . Conclusion : Liraglutide is well tolerated , sustains weight loss over 2 years and improves cardiovascular risk factors AIM We investigated the relationship between weight change and related factors in subjects with type 2 diabetes mellitus ( T2DM ) treated with liraglutide versus comparator diabetes therapies .  METHODS Twenty-six-week data from seven phase 3 , r and omized trials in the liraglutide T2DM development programme were analysed by trial and treatment group : liraglutide ( 1.2 and 1.8 mg ) , active comparator and placebo . Outcome measures included proportions of subjects in various weight change categories and their percentage weight change from baseline ; impact of body mass index ( BMI ) and gastrointestinal ( GI ) adverse events ( AEs ) on weight change and correlation of weight change with change in glycosylated haemoglobin ( HbA1c ) . RESULTS A number of subjects experienced > 5 % weight loss during the trials ( 24.4 % liraglutide 1.8 mg and 17.7 % liraglutide 1.2 mg ; 17.7 % exenatide , 10.0 % sitagliptin , 3.6 - 7.0 % sulphonylurea , 2.6 % thiazolidinedione and 2.6 % glargine ; 9.9 % placebo ) . More weight loss was seen with liraglutide 1.2 and 1.8 mg than with active comparators except exenatide . Across trials , higher initial BMI was associated with slightly greater weight loss with liraglutide . Mean weight loss increased slightly the longer GI AEs persisted . Although HbA1c reduction was slightly larger in higher weight loss categories across treatments ( including placebo ) , sample sizes were small and no clear correlation could be determined . Liraglutide-treated subjects experienced additional HbA1c reduction beyond that which appeared weight induced ; thus , not all HbA1c-lowering effect appears weight mediated . CONCLUSIONS The majority of liraglutide-treated T2DM subjects experienced weight loss in this analysis . Weight loss was greater and occurred more in glucagon-like peptide-1 receptor agonist-treated subjects than in active comparator-treated subjects OBJECTIVE To investigate the effect of treatment with the glucagon-like peptide 1 receptor agonist exenatide on weight loss and metabolic parameters in obese nondiabetic women . RESEARCH DESIGN AND METHODS Forty-one obese women ( aged 48 ± 11 years and BMI 33.1 ± 4.1 kg/m2 ) participated in a 35-week r and omized , double-blind , placebo-controlled , crossover study , including two 16-week treatment periods separated by a 3-week washout period . There was no lifestyle intervention . The primary outcome was change in body weight . RESULTS Subjects treated with exenatide lost an average of 2.49 ± 0.66 kg compared with a 0.43 ± 0.63 kg weight gain during placebo treatment . Weight loss  with exenatide treatment was noted at 2 weeks . The degree of weight loss could be stratified . A total of 30 % of subjects were high responders who lost ≥5 % body weight ( −7.96 ± 0.52 % ) , 39 % were moderate responders who lost < 5 % body weight ( −2.43 ± 0. 
    Output:
    
Participants in GLP-1RA groups achieved a larger weight loss than those in control groups ( -2.85 kg , 95%CI -3.55 to -2.14 ) , and liraglutide may work in a dose-dependent fashion .
GLP-1RAs also reduced body mass index ( BMI ) and waist circumferences ( WC ) and benefited systolic blood pressure and triglyceride regulation .
But GLP-1RAs were associated with increased nausea and vomiting events .
GLP-1 mimetics induce a weight loss in addition to BMI and WC reduction in obese/overweight adults without diabetes .