***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: Introduction The efficacy and safety of taspoglutide , a long-acting human glucagon-like peptide-1 analog , were compared with sitagliptin or placebo , as adjunct to metformin , in patients with inadequately controlled type 2 diabetes . Methods In this r and omized , double-blind , double-dummy , parallel-group trial , patients were r and omized to taspoglutide 10 mg once weekly ( QW ) , 20 mg QW , 100 mg sitagliptin once daily ( QD ) , or placebo for 24 weeks , followed by 28-week short-term and 104-week long-term extension periods . The primary endpoint was change in glycosylated hemoglobin ( HbA1c ) after 24 weeks . Results In this study , 666 patients ( baseline HbA1c , 7.96 % [ SD , 0.87 ] ; fasting plasma glucose , 9.61 mmol/L [ 2.56 ] ; body weight , 92.4 kg [ 19.3 ] ) were r and omized to taspoglutide 10 mg QW ( n = 190 ) , 20 mg QW ( n = 198 ) , 100 mg sitagliptin QD ( n = 185 ) , or placebo ( n = 93 ) for 24 weeks . After 24 weeks , least squares mean ( SE ) HbA1c reductions were greater with taspoglutide 10 mg ( −1.23 % [ 0.06 ] ) and 20 mg ( −1.30 % [ 0.06 ] ) versus sitagliptin ( −0.89 % [ 0.06 ] ) or placebo ( −0.10 % [ 0.08 ] ) . Mean treatment differences with taspoglutide 10 mg and 20 mg were −0.34 ( 95 % confidence intervals [ CI ] : −0.49 , −0.19 ) and −0.41 ( −0.56 , −0.26 ) versus sitagliptin ; and −1.13 ( −1.31 , −0.95 ) and −1.20 ( −1.38 , −1.02 ) versus placebo . Weight loss was greater with taspoglutide 10 mg ( −1.8 kg [ 0.3 ] ) and 20 mg ( −2.6 kg [ 0.3 ] ) than sitagliptin ( −0.9 kg [ 0.3 ] ) or placebo ( −0.5 kg [ 0.4 ] ) . Effects on HbA1c and weight loss continued through 52 weeks of treatment . No cases of severe hypoglycemia occurred with any active treatment . Gastrointestinal adverse events , and allergic and injection-site reactions were higher in the taspoglutide groups , causing higher discontinuation rates . Anti-taspoglutide antibodies were confirmed in 46 % of patients . Conclusion Taspoglutide demonstrated better efficacy on glycemic control and weight loss than sitagliptin , but a high incidence of adverse events led to high discontinuation rates . The safety profile of taspoglutide in this trial was similar to other trials in the clinical program , and led to the discontinuation of dosing Aims : Most treatments for type 2 diabetes  fail over time , necessitating combination therapy . We investigated the safety , tolerability and efficacy of liraglutide monotherapy compared with glimepiride monotherapy over 2 years OBJECTIVE Study the effects of exenatide ( EXE ) plus rosiglitazone ( ROSI ) on β-cell function and insulin sensitivity using hyperglycemic and euglycemic insulin clamp techniques in participants with type 2 diabetes on metformin . RESEARCH DESIGN AND METHODS In this 20-week , r and omized , open-label , multicenter study , participants ( mean age , 56 ± 10 years ; weight , 93 ± 16 kg ; A1C , 7.8 ± 0.7 % ) continued their metformin regimen and received either EXE 10 μg b.i.d . ( n = 45 ) , ROSI 4 mg b.i.d . ( n = 45 ) , or EXE 10 μg b.i.d . + ROSI 4 mg b.i.d . ( n = 47 ) . Seventy-three participants underwent clamp procedures to quantitate insulin secretion and insulin sensitivity . RESULTS A1C declined in all groups ( P < 0.05 ) , but decreased most with EXE+ROSI ( EXE+ROSI , −1.3 ± 0.1 % ; ROSI , −1.0 ± 0.1 % , EXE , −0.9 ± 0.1 % ; EXE+ROSI vs. EXE or ROSI , P < 0.05 ) . ROSI result ed in weight gain , while EXE and EXE+ROSI  result ed in weight loss ( EXE , −2.8 ± 0.5 kg ; EXE+ROSI , −1.2 ± 0.5 kg ; ROSI , + 1.5 ± 0.5 kg ; P < 0.05 between and within all groups ) . At week 20 , 1st and 2nd phase insulin secretion was significantly higher in EXE and EXE+ROSI versus ROSI ( both P < 0.05 ) . Insulin sensitivity ( M value ) was significantly higher in EXE+ROSI versus EXE ( P = 0.014 ) . CONCLUSIONS Therapy with EXE+ROSI offset the weight gain observed with ROSI and elicited an additive effect on glycemic control with significant improvements in β-cell function and insulin sensitivity 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 The aim of this study was to compare the efficacy and safety of once-daily human glucagon-like peptide-1 analogue liraglutide with dipeptidyl peptidase-4 inhibitor sitagliptin , each added to metformin , over 52 weeks in individuals with type 2 diabetes . Methods In an open-label , parallel-group trial , metformin-treated participants were r and omised to liraglutide 1.2 mg/day ( n= 225 ) , liraglutide 1.8 mg/day ( n= 221 ) or sitagliptin 100 mg/day ( n= 219 ) for 26 weeks ( main phase ) . Participants continued the same treatment in a 26-week extension . Results Liraglutide ( 1.2 or 1.8 mg ) was superior to sitagliptin for reducing HbA1c from baseline ( 8.4–8.5 % ) to 52 weeks : −1.29 % and −1.51 % vs. −0.88 % respectively . Estimated mean treatment differences between liraglutide and sitagliptin were as follows : −0.40 % ( 95 % confidence interval −0.59 to −0.22 ) for 1.2 mg and −0.63 % ( −0.81 to −0.44 ) for 1.8 mg ( both p < 0.0001 ) . Weight loss was greater with liraglutide 1.2 mg ( −2.78 kg ) and 1.8 mg ( −3.68 kg ) than sitagliptin ( −1.16 kg ) ( both p < 0.0001 ) . Diabetes Treatment Satisfaction Question naire scores increased significantly more with liraglutide 1.8 mg than with sitagliptin ( p = 0.03 ) . Proportions of participants reporting adverse events were generally comparable ; minor hypoglycaemia was 8.1 % , 8.3 % and 6.4 % for liraglutide 1.2 mg , 1.8 mg and sitagliptin respectively . Gastrointestinal side effects , mainly nausea , initially occurred more frequently with liraglutide , but declined after several weeks . Conclusion Liraglutide provides greater sustained glycaemic control and body weight reduction over 52 weeks . Treatment satisfaction was significantly greater with 1.8 mg liraglutide , similar to 26-week results . The safety profiles of liraglutide and sitagliptin are consistent with previous reports OBJECTIVE —The efficacy and safety of adding liraglutide ( a glucagon-like peptide-1 receptor agonist ) to metformin were compared with addition of placebo or glimepiride to metformin in subjects previously treated with oral antidiabetes ( OAD ) therapy . RESEARCH DESIGN AND METHODS —In this 26-week , double-blind , double-dummy , placebo- and active-controlled , parallel-group trial , 1,091 subjects were r and omly assigned ( 2:2:2:1:2 ) to once-daily liraglutide ( either 0.6 , 1.2 , or 1.8 mg/day injected subcutaneously ) , to placebo , or to glimepiride ( 4 mg once daily ) . All treatments were in combination therapy with metformin ( 1 g twice daily ) . Enrolled subjects ( aged 25–79 years ) had type 2 diabetes , A1C of 7–11 % ( previous OAD monotherapy for ≥3 months ) or 7–10 % ( previous OAD combination therapy for ≥3 months ) , and BMI ≤40 kg/m2 .  RESULTS —A1C values were significantly reduced in all liraglutide groups versus the placebo group ( P < 0.0001 ) with mean decreases of 1.0 % for 1.8 mg liraglutide , 1.2 mg liraglutide , and glimepiride and 0.7 % for 0.6 mg liraglutide and an increase of 0.1 % for placebo . Body weight decreased in all liraglutide groups ( 1.8–2.8 kg ) compared with an increase in the glimepiride group ( 1.0 kg ; P < 0.0001 ) . The incidence of minor hypoglycemia  with liraglutide ( ∼3 % ) was comparable to that with placebo but less than that with glimepiride ( 17 % ; P < 0.001 ) . Nausea was reported by 11–19 % of the liraglutide-treated subjects versus 3–4 % in the placebo and glimepiride groups . The incidence of nausea declined over time . CONCLUSIONS —In subjects with type 2 diabetes , once-daily liraglutide induced similar glycemic control , reduced body weight , and lowered the occurrence of hypoglycemia compared with glimepi 
    Output:
    
Overall , all GLP-1 RAs except for albiglutide increased the risk of hypoglycemia when compared to placebo .
Reduction in the incidence of hypoglycemia was found for all GLP-1 RAs versus insulin ( except for dulaglutide ) and sulphonylureas .
For the incidence of treatment discontinuation , increase was found for exenatide , liraglutide , lixisenatide and taspoglutide versus placebo , insulin and sitagliptin .
For glycemic level , decrease was found for all GLP-1 RAs versus placebo .
Dulaglutide , exenatide long-acting release ( exe_lar ) , liraglutide and taspoglutide had significant lowering effect when compared with sitagliptin ( HbA1c<7.0 % ) and insulin ( HbA1c<6.5 % ) .
Finally , according to SUCRAs , placebo , thiazolidinediones and albiglutide had the best decrease effect on hypoglycemia ;  sulphanylureas , sitagliptin and insulin decrease the incidence of treatment discontinuation most ; exe_lar and dulaglutide had the highest impact on glycemic level among 13 treatments .
Among 13 treatments , GLP-1 RAs had a significant reduction with glycemic level but a slight increase effect on hypoglycemia and treatment discontinuation .
While albiglutide had the best decrease effect on hypoglycemia and treatment discontinuation among all GLP-1 RAs .