***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 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 Aim To confirm the superiority , compared with placebo , of adding liraglutide to pre‐existing basal insulin analogue ± metformin in adults with inadequately controlled type 2 diabetes [ glycated haemoglobin ( HbA1c ) 7.0–10.0 % ( 53–86 mmol/mol ) ] . Methods In this 26‐week , double‐blind , parallel‐group study , conducted in clinics or hospitals , 451 subjects were r and omized 1 : 1 to once‐daily liraglutide 1.8 mg ( dose escalated from 0.6 and 1.2 mg/day , respectively , for 1 week each ; n = 226 ) or placebo ( n = 225 ) added to their pre‐existing basal insulin analogue ( ≥20 U/day ) ± metformin ( ≥1500 mg/day ) . After r and omization , insulin adjustments above the pre‐ study dose were not allowed . The primary endpoint was HbA1c change . Results After 26 weeks , HbA1c decreased more with liraglutide [ −1.3 % ( −14.2 mmol/mol ) ] than with placebo [ −0.1 % ( −1.2 mmol/mol ) ; p < 0.0001 ] . More subjects on liraglutide reached HbA1c targets : < 7.0 % ( 59 % vs 14 % ; p < 0.0001 ) and ≤6.5 % ( 43 % vs 4 % ; p < 0.0001 ) using slightly less insulin ( 35.8 IU vs 40.1 IU ) . Greater decreases from baseline ( estimated treatment differences vs placebo ; p < 0.0001 ) occurred in fasting plasma glucose ( −1.3 mmol/l ) , seven‐point glucose profiles ( −1.6 mmol/l ) , body weight ( −3.1 kg ) and systolic blood pressure ( −5.0 mmHg ) . Transient gastrointestinal adverse events ( nausea : 22.2 % vs 3.1 % ) and minor hypoglycaemia ( 18.2 % vs 12.4 % ) were more frequent with liraglutide than placebo , and pulse increased ( 4.5 beats/min ) compared with placebo . No severe hypoglycaemia or pancreatitis occurred . Conclusions Adding liraglutide to a basal insulin analogue ± metformin significantly improved glycaemic control , body weight and systolic blood pressure compared with placebo . Typical gastrointestinal symptoms and minor hypoglycaemia were more frequent with liraglutide Aims To evaluate the safety and efficacy of once‐weekly dulaglutide 1.5 mg , a long‐acting glucagon‐like peptide‐1 receptor agonist , compared with placebo in patients with type 2 diabetes ( T2D ) on glimepiride monotherapy . Methods This phase III , r and omized ( 4 : 1 ; dulaglutide  : placebo ) , double‐blind , placebo‐controlled , 24‐week study compared the safety and efficacy of once‐weekly dulaglutide 1.5 mg with placebo in  sulphonylurea‐treated ( ≥half‐maximal dose , stable ≥3 months ) patients ( N = 300 ) with T2D and inadequate glycaemic control [ glycated haemoglobin ( HbA1c ) ≥7.5 and ≤9.5 % ( ≥58 mmol/mol and ≤80 mmol/mol ) ] . Analysis was carried out according to intention‐to‐treat . Results At baseline , the mean participant age was 58 years ; mean HbA1c was 8.4 % ( 68 mmol/mol ) and mean weight was 85.5 kg . Dulaglutide 1.5 mg was superior to placebo at 24 weeks for HbA1c reduction from baseline with a between‐group HbA1c difference of −1.3 % [ 95 % confidence interval ( CI ) −1.6 , −1.0 ] or ‐14 mmol/mol ( 95 % CI −17 , −11 ) ; p < 0.001 . A greater proportion of participants in the dulaglutide group reached an HbA1c level of < 7.0 % ( 53 mmol/mol ) compared with placebo ( 55.3 % vs 18.9 % ; p < 0.001 ) . Dulaglutide significantly decreased fasting serum glucose from baseline compared with placebo ( between‐group difference −1.86 mmol/l ( 95 % CI −2.58 , −1.14 ) or −33.54 mg/dl ( 95 % CI −46.55 , −20.53 ) ; p < 0.001 . Weight was decreased significantly from baseline in the dulaglutide group ( p < 0.001 ) ; the between‐group difference was not significant . The most common treatment‐emergent adverse events for dulaglutide 1.5 mg were gastrointestinal : nausea ( 10.5 % ) , diarrhoea ( 8.4 % ) and eructation ( 5.9 % ) . Total hypoglycaemia was higher with dulaglutide 1.5 mg vs placebo ( 2.37 and 0.07 events/participant/year , respectively ; p = 0.025 ) . No severe hypoglycaemia was reported . Conclusions Once‐weekly dulaglutide 1.5 mg had a favourable benefit/risk profile when added to glimepiride monotherapy OBJECTIVE To assess the effect of a 4-week adjunctive therapy of exenatide ( EXE ) ( 5–10 μg b.i.d . ) or sitagliptin ( SITA ) ( 100 mg once daily ) in response to a st and ardized breakfast meal challenge in 48 men or women with type 2 diabetes receiving insulin glargine ( GLAR ) + metformin ( MET ) .  RESEARCH DESIGN AND METHODS This was a single-center , r and omized , open-label , active comparator – controlled study with a three-arm parallel group design , consisting of : screening , 4- to 8-week run-in period , 4-week treatment period , and follow-up . In all three groups , the GLAR dose was titrated according to an algorithm ( fasting blood glucose ≤100 mg/dl ) . RESULTS The unadjusted 6-h postpr and ial blood glucose excursion of both GLAR + MET + EXE and GLAR + MET + SITA was statistically significantly smaller than that of GLAR + MET ( 606 ± 104 vs. 612 ± 133 vs. 728 ± 132 mg/dl/h ; P = 0.0036 and 0.0008 ) . A1C significantly decreased in all three groups ( P < 0.0001 ) , with the greatest reduction of −1.9 ± 0.7 under GLAR + MET + EXE ( GLAR + MET + SITA −1.5 ± 0.7 ; GLAR + MET −1.2 ± 0.5%-points ; GLAR + MET + EXE vs. GLAR + MET P = 0.0154 ) . The American Diabetes Association A1C target of < 7.0 % was reached by 80.0 , 87.5 , and 62.5 % of subjects , respectively . GLAR + MET + EXE had the highest number ( 47 ) of adverse events , mostly gastrointestinal ( 56 % ) with one dropout . GLAR + MET or GLAR + MET + SITA only had 10 and 12 adverse events , respectively , and no dropouts . Hypoglycemia ( blood glucose < 50 mg/dl ) rates were low and comparable among groups . Weight decreased with GLAR + 
    Output:
    
Compared with placebo , all GLP-1RAs except albiglutide reduced weight and increased the risk of hypoglycaemia and gastrointestinal side effects , and all agents except dulaglutide and taspoglutide reduced systolic blood pressure .
When all GLP-1RAs were compared with each other , no clinical ly meaningful differences were observed in weight loss , blood pressure reduction or hypoglycaemia risk .
Albiglutide had the lowest risk of nausea and diarrhoea and once-weekly exenatide the lowest risk of vomiting .
CONCLUSIONS The RCTs in the present analysis show that all GLP-1RAs  improve glycaemic control , reduce body weight and increase the risk of adverse gastrointestinal symptoms compared with placebo .
Although there were no differences when short-acting agents were compared with each other or when long-acting agents were compared with each other , dulaglutide , liraglutide and once-weekly exenatide were superior to twice-daily exenatide and lixisenatide at lowering HbA1c and FPG levels .
There were no differences in hypoglycaemia between these 3 agents , whilst once-weekly exenatide had the lowest risk of vomiting .