***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: 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 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 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 glimepiride , when both had background therapy of metformin OBJECTIVE Traditional blood glucose – lowering agents do not sustain adequate glycemic control in most type 2 diabetic patients . Pre clinical studies with exenatide have suggested sustained improvements in β-cell function . We investigated the effects of 52 weeks of treatment with exenatide or insulin glargine followed by an off-drug period on hyperglycemic clamp – derived measures of β-cell function , glycemic control , and body weight . RESEARCH DESIGN AND METHODS Sixty-nine metformin-treated patients with type 2 diabetes were r and omly assigned to exenatide ( n = 36 ) or insulin glargine ( n = 33 ) . β-Cell function was measured during an arginine-stimulated hyperglycemic clamp at week 0 , at week 52 , and after a 4-week off-drug period . Additional end points included effects on glycemic control , body weight , and safety . RESULTS Treatment-induced change in combined glucose- and arginine-stimulated C-peptide secretion was 2.46-fold ( 95 % CI 2.09–2.90 , P < 0.0001 ) greater after a 52-week exenatide treatment compared with insulin glargine treatment . Both exenatide and insulin glargine reduced A1C similarly : −0.8 ± 0.1 and −0.7 ± 0.2 % , respectively ( P = 0.55 ) . Exenatide  reduced body weight compared with insulin glargine ( difference −4.6 kg , P < 0.0001 ) . β-Cell function measures returned to pretreatment values in both groups after a 4-week off-drug period . A1C and body weight rose to pretreatment values 12 weeks after discontinuation of either exenatide or insulin glargine therapy . CONCLUSIONS Exenatide  significantly improves β-cell function during 1 year of treatment compared with titrated insulin glargine . After cessation of both exenatide and insulin glargine  therapy , β-cell function and glycemic control returned to pretreatment values , suggesting that ongoing treatment is necessary to maintain the beneficial effects of either therapy AIMS Patient-reported outcomes from clinical trials offer insight into the impact of disease on health-related quality of life , including treatment satisfaction . This patient-reported outcomes evaluation was a sub study of a 26-week r and omized , open-label trial comparing the once-daily injectable human GLP-1 analogue liraglutide with once-daily oral sitagliptin , both added to metformin . The patient reported outcomes sub study aim ed to evaluate treatment satisfaction using the Diabetes Treatment Satisfaction Question naire ( DTSQ ) at baseline and 26 weeks . METHODS In the main 26-week 
    Output:
    
GLP-1 analogues are associated with a small increase in heart rate and modest reductions in body weight and blood pressure .