***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 The cardiovascular effects of adding once‐weekly treatment with exenatide to usual care in patients with type 2 diabetes are unknown . METHODS We r and omly assigned patients with type 2 diabetes , with or without previous cardiovascular disease , to receive subcutaneous injections of extended‐release exenatide at a dose of 2 mg or matching placebo once weekly . The primary composite outcome was the first occurrence of death from cardiovascular causes , nonfatal myocardial infa rct ion , or nonfatal stroke . The co primary hypotheses were that exenatide , administered once weekly , would be noninferior to placebo with respect to safety and superior to placebo with respect to efficacy . RESULTS In all , 14,752 patients ( of whom 10,782 [ 73.1 % ] had previous cardiovascular disease ) were followed for a median of 3.2 years ( interquartile range , 2.2 to 4.4 ) . A primary composite outcome event occurred in 839 of 7356 patients ( 11.4 % ; 3.7 events per 100 person‐years ) in the exenatide group and in 905 of 7396 patients ( 12.2 % ; 4.0 events per 100 person‐years ) in the placebo group ( hazard ratio , 0.91 ; 95 % confidence interval [ CI ] , 0.83 to 1.00 ) , with the intention‐to‐treat analysis indicating that exenatide , administered once weekly , was noninferior to placebo with respect to safety ( P<0.001 for noninferiority ) but was not superior to placebo with respect to efficacy ( P=0.06 for superiority ) . The rates of death from cardiovascular causes , fatal or nonfatal myocardial infa rct ion , fatal or nonfatal stroke , hospitalization for heart failure , and hospitalization for acute coronary syndrome , and the incidence of acute pancreatitis , pancreatic cancer , medullary thyroid carcinoma , and serious adverse events did not differ significantly between the two groups . CONCLUSIONS Among patients with type 2 diabetes with or without previous cardiovascular disease , the incidence of major adverse cardiovascular events did not differ significantly between patients who received exenatide and those who received placebo . ( Funded by Amylin Pharmaceuticals ; EXSCEL Clinical Trials.gov number , NCT01144338 . Rationale Post-stroke hyperglycemia occurs in up to 50 % of patients presenting with acute ischemic stroke . It reduces the efficacy of thrombolysis , increases infa rct size , and worsens clinical outcomes . Insulin-based therapies have generally not been beneficial in treating post-stroke hyperglycemia as they are difficult to implement , may cause hypoglycaemia , possibly increase mortality and worsen clinical outcomes . Exenatide may be a safer , simpler , and more effective alternative to insulin in acute ischemic stroke . Design TEXAIS is a three year , Phase 2 , multi-center , prospect i ve , r and omized , open label , blinded end-point trial comparing exenatide to st and ard of care . It aims to recruit 528 patients with a primary end point of major neurological improvement at 7 days defined as a ≥8-point improvement in NIHSS score , or NIHSS 0–1 . Secondary outcomes of hyper- and hypoglycaemia at 5 days and NIHSS and mRS at 90 days will be measured . The treatment arm will receive exenatide 5 µg subcutaneously twice daily . The control arm will receive st and ard stroke unit care . Continuous glucose monitors will track the dynamic variability of glucose . Conclusion TEXAIS aims to show that exenatide is safe and effective in the treatment of post-stroke hyperglycemia . It has been design ed to be highly generalizable with an ability to enroll a large percentage of patients with acute ischemic stroke , regardless of admission blood glucose level , diabetes status , or stroke severity , with very low risk of hypoglycemia . Trial registration : Clinical Trials.gov/ANZCTR BACKGROUND Glucagon-like peptide 1 receptor agonists differ in chemical structure , duration of action , and in their effects on clinical outcomes . The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown . We aim ed to determine the safety and efficacy of albiglutide in preventing cardiovascular death , myocardial infa rct ion , or stroke . METHODS We did a double-blind , r and omised , placebo-controlled trial in 610 sites across 28 countries . We r and omly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease ( at a 1:1 ratio ) to groups that either received a subcutaneous injection of albiglutide ( 30 - 50 mg , based on glycaemic response and tolerability ) or of a matched volume of placebo once a week , in addition to their st and ard care . Investigators used an interactive voice or web response system to obtain treatment assignment , and patients and all study investigators were masked to their treatment allocation . We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death , myocardial infa rct ion , or stroke , which was assessed in the intention-to-treat population . If non-inferiority was confirmed by an upper limit of the 95 % CI for a hazard ratio of less than 1·30 , closed testing for superiority was prespecified . This study is registered with Clinical Trials.gov , number NCT02465515 . FINDINGS Patients were screened between July 1 , 2015 , and Nov 24 , 2016 . 10 793 patients were screened and 9463 participants were enrolled and r and omly assigned to groups : 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo . On Nov 8 , 2017 , it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued , and participants returned for a final visit and discontinuation from study treatment ; the last patient visit was on March 12 , 2018 . These 9463 patients , the intention-to-treat population , were evaluated for a median duration of 1·6 years and were assessed for the primary outcome . The primary composite outcome occurred in 338 ( 7 % ) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 ( 9 % ) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group ( hazard ratio 0·78 , 95 % CI 0·68 - 0·90 ) , which indicated that albiglutide was superior to placebo ( p<0·0001 for non-inferiority ; p=0·0006 for superiority ) . The incidence of acute pancreatitis ( ten patients in the albiglutide group and seven patients in the placebo group ) , pancreatic cancer ( six patients in the albiglutide group and five patients in the placebo group ) , medullary thyroid carcinoma ( zero patients in both groups ) , and other serious adverse events did not differ between the two groups . There were three ( < 1 % ) deaths in the placebo group that were assessed by investigators , who were masked to study drug assignment , to be treatment-related and two ( < 1 % ) deaths in the albiglutide group . INTERPRETATION In patients with type 2 diabetes and cardiovascular disease , albiglutide was superior to placebo with respect to major adverse cardiovascular events . Evidence -based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes . FUNDING GlaxoSmithKline BACKGROUND Cardiovascular morbidity and mortality are higher among patients with type 2 diabetes , particularly those with concomitant cardiovascular diseases , than in most other population s. We assessed the effects of lixisenatide , a glucagon-like peptide 1-receptor agonist , on cardiovascular outcomes in patients with type 2 diabetes who had had a recent acute coronary event . METHODS We r and omly assigned patients with type 2 diabetes who had had a myocardial infa rct ion or who had been hospitalized for unstable angina within the previous 180 days to receive lixisenatide or placebo in addition to locally determined st and ards of care . The trial was design ed with adequate statistical power to assess whether lixisenatide was noninferior as well as superior to placebo , as defined by an upper boundary of the 95 % confidence interval for the hazard ratio of less than 1.3 and 1.0 , respectively , for the primary composite end point of cardiovascular death , myocardial infa rct ion , stroke , or hospitalization for unstable angina . RESULTS The 6068 patients who underwent r and omization were followed for a median of 25 months . A primary end-point event occurred in 406 patients ( 13.4 % ) in the lixisenatide group and in 399 ( 13.2 % ) in the placebo group ( hazard ratio , 1.02 ; 95 % confidence interval [ CI ] , 0.89 to 1.17 ) , which showed the noninferiority of lixisenatide to placebo ( P<0.001 ) but did not show superiority ( P=0.81 ) . There were no significant between-group differences in the rate of hospitalization for heart failure ( hazard ratio in the lixisenatide group , 0.96 ; 95 % CI , 0.75 to 1.23 ) or the rate of death ( hazard ratio , 0.94 ; 95 % CI , 0.78 to 1.13 ) . Lixisenatide was not associated with a higher rate of serious adverse events or severe hypoglycemia , pancreatitis , pancreatic neoplasms , or allergic reactions than was placebo . CONCLUSIONS In patients with type 2 diabetes and a recent acute coronary syndrome , the addition of lixisenatide to usual care did not significantly alter the rate of major cardiovascular events or other serious adverse events . ( Funded by Sanofi ; ELIXA Clinical Trials.gov number , NCT01147250 . ) OBJECTIVE The effect of additional treatment with oral hypoglycemic agents on the progression of atherosclerosis remains unknown in insulin-treated patients with type 2 diabetes mellitus ( T2DM ) . We assessed the effects of sitagliptin , a dipeptidyl peptidase 4 inhibitor , on carotid intima-media thickness ( IMT ) in T2DM . RESEARCH DESIGN AND METHODS This prospect i ve , r and omized , open-label , blinded end point , multicenter , parallel-group , comparative study included 282 insulin-treated patients with T2DM free of a history of apparent cardiovascular diseases who were recruited at 12 clinical units and r and omly allocated to either the sitagliptin group ( n = 142 ) or the control group ( n = 140 ) . The primary outcomes were changes in mean and maximum IMT of the common carotid artery measured by echography at the end of a 104-week treatment period . RESULTS Sitagliptin had a more potent glucose-lowering effect compared with the conventional treatment ( −0.5 ± 1.0 % vs. −0.2 ± 0.9 % ; P = 0.004 ) , without increasing hypoglycemic episodes or body weight . Changes in the mean and left maximum IMT , but not right maximum IMT , of the common carotid arteries were significantly greater after sitagliptin treatment compared with conventional treatment ( −0.029 [ SE 0.013 ] vs. 0.024 [ 0.013 ] mm [ P = 0.005 ] ; −0.065 [ 0.027 ] vs. 0.022 [ 0.026 ] mm [ P = 0.021 ] ; −0.007 [ 0.031 ] vs. 0.027 [ 0.031 ] mm [ P = 0.45 ] , respectively ) . Over 104 weeks , sitagliptin , but not conventional treatment , significantly reduced the mean IMT and left maximum IMT of common carotid arteries relative to the baseline . CONCLUSIONS Sitagliptin attenuated the progression of carotid IMT in insulin-treated patients with T2DM free of apparent cardiovascular disease compared with conventional treatment 
    Output:
    
The findings of this meta- analysis support the evidence from earlier experimental studies calling attention to potential ' stroke protective ' effects from treatment with GLP-1R