***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: AIMS To investigate the efficacy and safety of linagliptin , a dipeptidyl peptidase-4 inhibitor , in type 2 diabetes mellitus ( T2DM ) patients for whom metformin was inappropriate . METHODS This 1-year double-blind study ( Clinical Trials.gov , NCT00740051 ) enrolled T2DM patients with inadequate glycaemic control , treatment-naïve [ glycated haemoglobin ( HbA1c ) 7.0 - 10.0 % ] or previously treated with one oral antidiabetes drug ( HbA1c 6.5 - 9.0 % before washout ) , ineligible for metformin because of contraindications ( e.g. renal impairment ) or previous intolerable side effects . Patients were r and omized to monotherapy with linagliptin 5 mg once daily ( n = 151 ) or placebo  ( n = 76 ) for 18 weeks , after which placebo patients switched to glimepiride 1 - 4 mg once daily and treatments continued for another 34 weeks . The primary endpoint was change from baseline in HbA1c after 18 weeks ( full- analysis set , last observation carried forward ) . RESULTS At week 18 , adjusted mean difference in change from baseline HbA1c ( 8.1 % ) was -0.60 % ( 95 % confidence interval -0.88 , -0.32 ; p < 0.0001 ) ( -0.39 % with linagliptin , + 0.21 % with placebo ) . At week 52 , mean HbA1c was decreased from baseline in both groups [ linagliptin : -0.44 % ; placebo/glimepiride : -0.72 % ( observed cases ) ] . Adverse events occurred in 40.4 and 48.7 % of linagliptin and placebo patients , respectively , during the initial 18 weeks . During the 34-week extension , patients receiving linagliptin experienced less hypoglycaemia ( 2.2 % vs. 7.8 % ) and no weight gain ( mean change from baseline of -0.2 and + 1.3 kg , respectively ) compared with glimepiride patients . CONCLUSIONS In T2DM patients for whom metformin was inappropriate , linagliptin improved glycaemic control and was well tolerated , with less hypoglycaemia and relative weight loss compared with glimepiride OBJECTIVE To evaluate the effects of canagliflozin , a sodium-glucose cotransporter 2 inhibitor , in type 2 diabetes mellitus inadequately controlled with metformin monotherapy . RESEARCH DESIGN AND METHODS This was a double-blind , placebo-controlled , parallel-group , multicenter , dose-ranging study in 451 subjects r and omized to canagliflozin 50 , 100 , 200 , or 300 mg once daily ( QD ) or 300 mg twice daily ( BID ) , sitagliptin 100 mg QD , or placebo . Primary end point was change in A1C from baseline through week 12 . Secondary end points included change in fasting plasma glucose ( FPG ) , body weight , and overnight urinary glucose-to-creatinine ratio . Safety and tolerability were also assessed . RESULTS Canagliflozin was associated with significant reductions in A1C from baseline ( 7.6–8.0 % ) to week 12 : −0.79 , −0.76 , −0.70 , −0.92 , and −0.95 % for canagliflozin 50 , 100 , 200 , 300 mg QD and 300 mg BID , respectively , versus −0.22 % for placebo ( all P < 0.001 ) and −0.74 % for sitagliptin . FPG was reduced by −16 to −27 mg/dL , and body weight was reduced by −2.3 to −3.4 % , with significant increases in urinary glucose-to-creatinine ratio . Adverse events were transient , mild to moderate , and balanced across arms except for a non – dose-dependent increase in symptomatic genital infections with canagliflozin ( 3–8 % ) versus placebo and sitagliptin ( 2 % ) . Urinary tract infections were reported without dose dependency in 3–9 % of canagliflozin , 6 % of placebo , and 2 % of sitagliptin  arms . Overall incidence of hypoglycemia was low . CONCLUSIONS Canagliflozin added onto metformin significantly improved glycemic control in type 2 diabetes and was associated with low incidence of hypoglycemia and significant weight loss . The safety/tolerability profile of canagliflozin was favorable except for increased frequency of genital infections in females CONTEXT Dapagliflozin , a selective sodium-glucose cotransporter 2 ( SGLT2 ) inhibitor , reduces hyperglycemia in patients with type 2 diabetes mellitus ( T2DM ) by increasing urinary glucose excretion , and weight loss is a consistent associated finding . OBJECTIVES Our objectives were to confirm weight loss with dapagliflozin and establish through body composition measurements whether weight loss is accounted for by changes in fat or fluid components . DESIGN AND SETTING This was a 24-wk , international , multicenter , r and omized , parallel-group , double-blind , placebo-controlled study with ongoing 78-wk site- and patient-blinded extension period at 40 sites in five countries . PATIENTS Included were 182 patients with T2DM ( mean values : women 63.3 and men 58.6 yr of age ; hemoglobin A1c 7.17 % , body mass index 31.9 kg/m2 , and body weight 91.5 kg ) inadequately controlled on metformin . INTERVENTION Dapagliflozin 10 mg/d or placebo was added to open-label metformin for 24 wk . MAIN OUTCOME MEASURES Primary endpoint was total body weight ( TBW ) change from baseline at wk 24 . Key secondary endpoints were waist circumference and dual-energy x-ray absorptiometry total-body fat mass ( FM ) changes from baseline at wk 24 , and patient proportion achieving body weight reduction of at least 5 % at wk 24 . In a subset of patients , magnetic resonance assessment of visceral adipose tissue ( VAT ) and sc adipose tissue ( SAT ) volume and hepatic lipid content were also evaluated . RESULTS At wk 24 , placebo-corrected changes with dapagliflozin were as follows : TBW , -2.08 kg [ 95 % confidence interval (CI)=-2.84 to -1.31 ; P<0.0001 ] ; waist circumference , -1.52 cm ( 95 % CI=-2.74 to -0.31 ; P=0.0143 ) ; FM , -1.48 kg ( 95 % CI=-2.22 to -0.74 ; P=0.0001 ) ; proportion of patients achieving weight reduction of at least 5 % , + 26.2 % ( 95 % CI=15.5 to 36.7 ; P<0.0001 ) ; VAT , -258.4 cm3 ( 95 % CI=-448.1 to -68.6 ; nominal P=0.0084 ) ; SAT , -184.9 cm3 ( 95 % CI=-359.7 to -10.1 ; nominal P=0.0385 ) . In the dapagliflozin vs. placebo groups , respectively , serious adverse events were reported in 6.6 vs. 1.1 % ; events suggestive of vulvovaginitis , balanitis , and related genital infection in 3.3 vs. 0 % ; and lower urinary tract infections in 6.6 vs. 2.2 % . CONCLUSIONS Dapagliflozin reduces TBW , predominantly by reducing FM , VAT and SAT in T2DM inadequately controlled with metformin 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 UNLABELLED Inhibition of dipeptidyl peptidase-4 enhances the activity of incretin hormones , improving glycemic control in subjects with type 2 diabetes . This twelve-week r and omized , double-masked , placebo-controlled study assessed the efficacy and tolerability of the specific and potent oral dipeptidyl peptidase-4 inhibitor , vildagliptin ( 25 mg , bid , n=70 ) VS . placebo ( bid , n=28 ) in previously diet-treated subjects with type 2 diabetes . St and ardized meal tests were performed at baseline and endpoint . The between-group difference in adjusted mean change in HbA1c from baseline to endpoint was - 0.6 + /- 0.2 % ( p=0.0012 ) for the whole cohort ( baseline 8.0 % ) and -1.2 % for subjects with baseline HbA1c 8.0 - 9.5 % . Fasting glucose and mean pr and ial glucose were reduced by 1.1 + /- 0.4 ( p=0.0043 ) and 1.9 + /- 0.5 mmol/l ( p < 0.0001 ) , respectively . The between-group differences in corrected insulin response at peak glucose and mean pr and ial C-peptide were + 0.06 + /- 0.02 ( p=0.0258 ) and + 0.10 + /- 0.03 nmol/l ( p=0.0031 ) , respectively . Vildagliptin had no effect on fasting lipid levels or body weight . The incidence of adverse events was similar in subjects receiving placebo ( 71.4 % ) and vildagliptin ( 55.7 % ) . CONCLUSION monotherapy with vildagliptin is well tolerated and improves glycemic control in diet-treated subjects with type 2 diabetes . Concomitant improvements in beta-cell function were also observed . Subjects with higher baseline HbA1c levels showed greater response OBJECTIVE Dapagliflozin , a highly selective inhibitor of the renal sodium-glucose cotransporter-2 , increases urinary excretion of glucose and lowers plasma glucose levels in an insulin-independent manner . We evaluated the efficacy and safety of dapagliflozin in treatment-naive patients with type 2 diabetes . RESEARCH 
    Output:
    
Severe hypoglycaemia was rare not increased for any comparisons .
Conclusions Metformin and the simultaneous initiation of dual therapy , but not AHA used alone or as single add-on combination therapy , was associated with an increased risk of any hypoglycaemia relative to placebo