***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 : Assess the efficacy and safety of saxagliptin added to a submaximal sulphonylurea dose vs. uptitration of sulphonylurea monotherapy in patients with type 2 diabetes and inadequate glycaemic control with sulphonylurea monotherapy . Methods and patients : A total of 768 patients ( 18–77 years ; HbA1c screening ≥ 7.5 to ≤ 10.0 % ) were r and omised and treated with saxagliptin 2.5 or 5 mg in combination with glyburide 7.5 mg vs. glyburide 10 mg for 24 weeks . Blinded uptitration glyburide was allowed in the glyburide-only arm to a maximum total daily dose of 15 mg . Efficacy analyses were performed using ANCOVA and last-observation-carried-forward methodology . Results : At week 24 , 92 % of glyburide-only patients were uptitrated to a total glyburide dose of 15 mg/day . Saxagliptin 2.5 and 5 mg provided statistically significant adjusted mean decreases from baseline to week 24 vs. uptitrated glyburide , respectively , in HbA1c ( −0.54 % , −0.64 % vs. + 0.08 % ; both p < 0.0001 ) and fasting plasma glucose ( −7 , −10 vs. + 1 mg/dl ; p = 0.0218 and p = 0.002 ) . The proportion of patients achieving an HbA1c < 7 % was greater for saxagliptin 2.5 and 5 mg vs. uptitrated glyburide ( 22.4 % and 22.8 % vs. 9.1 % ; both p < 0.0001 ) . Postpr and ial glucose area under the curve was reduced for saxagliptin 2.5 and 5 mg vs. uptitrated glyburide ( −4296 and −5000 vs. + 1196 mg·min/dl ; both p < 0.0001 ) . Adverse event occurrence was similar across all groups . Reported hypoglycaemic events were not statistically significantly different for saxagliptin 2.5 ( 13.3 % ) and 5 mg ( 14.6 % ) vs. uptitrated glyburide ( 10.1 % ) . Conclusion : Saxagliptin added to submaximal glyburide therapy led to statistically significant improvements vs. uptitration of glyburide alone across key glycaemic parameters and was generally well tolerated AIM To assess the safety and efficacy of the potent and selective dipeptidyl peptidase-4 inhibitor linagliptin 5 mg when given for 24 weeks to patients with type 2 diabetes who were either treatment-naive or who had received one oral antidiabetes drug ( OAD ) . METHODS This multicentre , r and omized , parallel group , phase III study compared linagliptin  treatment ( 5 mg once daily , n = 336 ) with placebo ( n = 167 ) for 24 weeks in type 2 diabetes patients . Before r and omization , patients pretreated with one OAD underwent a washout period of 6 weeks , which included a placebo run-in period during the last 2 weeks . Patients previously untreated with an OAD underwent a 2-week placebo run-in period . The primary endpoint was the change in HbA1c from baseline after 24 weeks of treatment . RESULTS Linagliptin treatment result ed in a placebo-corrected change in HbA1c from baseline of -0.69 % ( p < 0.0001 ) at 24 weeks . In patients with baseline HbA1c ≥ 9.0 % , the adjusted reduction in HbA1c was 1.01 % ( p < 0.0001 ) . Patients treated with linagliptin were more likely to achieve a reduction in HbA1c of ≥0.5 % at 24 weeks than those in the placebo arm ( 47.1 and 19.0 % , respectively ; odds ratio , OR = 4.2 , p < 0.0001 ) . Fasting plasma glucose improved by -1.3 mmol/l ( p < 0.0001 ) with linagliptin vs. placebo , and linagliptin produced an adjusted mean reduction from baseline after 24 weeks in 2-h postpr and ial glucose of -3.2 mmol/l ( p < 0.0001 ) . Statistically significant and relevant treatment differences were observed for proinsulin/insulin ratio ( p = 0.025 ) , Homeostasis Model Assessment -%B ( p = 0.049 ) and disposition index ( p = 0.0005 ) . There was no excess of hypoglycaemic episodes with linagliptin vs. placebo and no patient required third-party intervention . Mild or moderate renal impairment did not influence the trough plasma levels of linagliptin . CONCLUSIONS Monotherapy with linagliptin produced a significant , clinical ly meaningful and sustained improvement in glycaemic control , accompanied by enhanced parameters of β-cell function . The safety profile of linagliptin was comparable with that of placebo AIM The study aim was to evaluate the efficacy and safety of initial combination therapy with saxagliptin + metformin vs. saxagliptin or metformin monotherapy in treatment-naïve patients with type 2 diabetes ( T2D ) and inadequate glycaemic control . METHODS In this multicentre , r and omized , double-blind , active-controlled phase 3 trial , 1306 treatment-naïve patients with T2D > or=18 to < or=77 years , glycosylated haemoglobin ( HbA1c ) > or=8 to < or=12 % , fasting C-peptide concentration > or=1.0 ng/ml , body mass index < or=40 kg/m(2 ) were r and omized to receive saxagliptin 5 mg + metformin 500 mg , saxagliptin 10 mg + metformin 500 mg , saxagliptin 10 mg + placebo or metformin 500 mg + placebo for 24 weeks . From weeks 1 - 5 , metformin was uptitrated in 500-mg/day increments to 2000 mg/day maximum in the saxagliptin 5 mg + metformin , saxagliptin 10 mg + metformin and metformin + placebo treatment groups . The main outcome measure was HbA1c change from baseline to week 24 . Selected secondary outcomes included change from baseline to week 24 in fasting plasma glucose ( FPG ) , proportion of patients achieving HbA1c < 7 % and postpr and ial glucose area under the curve ( PPG-AUC ) . RESULTS At 24 weeks , saxagliptin 5 mg + metformin and saxagliptin 10 mg + metformin demonstrated statistically significant adjusted mean decreases vs. saxagliptin 10 mg and metformin monotherapies in HbA1c ( -2.5 and -2.5 % vs. -1.7 and -2.0 % , all p < 0.0001 vs. monotherapy ) and FPG ( -60 and -62 mg/dl vs. -31 and -47 mg/dl , both p < 0.0001 vs. saxagliptin 10 mg ; p = 0.0002 saxagliptin 5 mg + metformin vs. metformin ; p < 0.0001 saxagliptin 10 mg + metformin vs. metformin ) . Proportion of patients achieving an HbA1c < 7 % was 60.3 and 59.7 % , respectively , for saxagliptin 5 mg + metformin and saxagliptin 10 mg + metformin ( all p < 0.0001 vs. monotherapy ) . PPG-AUC was significantly reduced [ -21,080 mg x min/dl ( saxagliptin 5 mg + metformin ) and -21,336 mg x min/dl ( saxagliptin 10 mg + metformin ) vs. -16,054 mg x min/dl ( saxagliptin 10 mg ) and -15,005 mg x min/dl ( metformin ) , all p < 0.0001 vs. monotherapy ] . Adverse event occurrence was similar across all groups . Hypoglycaemic events were infrequent . CONCLUSION Saxagliptin + metformin as initial therapy led to statistically significant improvements compared with either treatment alone across key glycaemic parameters with a tolerability profile similar to the monotherapy components AIM To assess the efficacy and safety of a 24-week treatment with sitagliptin , a highly selective once-daily oral dipeptidyl peptidase-4 ( DPP-4 ) inhibitor , in patients with type 2 diabetes who had inadequate glycaemic control [ glycosylated haemoglobin ( HbA(1c ) ) > or=7.5 % and < or=10.5 % ] while on glimepiride alone or in combination with metformin .  METHODS After a screening , diet/exercise run-in and drug wash-off period , a glimepiride + /- metformin dose titration/stabilization period and a 2-week , single-blind placebo run-in , 441 patients ( of ages 18 - 75 years ) were r and omized to receive the addition of sitagliptin 100 mg once daily or placebo in a 1 : 1 ratio for 24 weeks . Of these patients , 212 were on glimepiride ( > or=4 mg/day ) monotherapy and 229 were on glimepiride ( > or=4 mg/day ) plus metformin ( > or=1,500 mg/day ) combination therapy .  Patients exceeding pre-specified glycaemic thresholds during the double-blind treatment period were provided open-label rescue therapy ( pioglitazone ) until study end . The primary efficacy analysis evaluated the change in HbA(1c ) from baseline to Week 24 . Secondary efficacy endpoints included fasting plasma glucose ( FPG ) , 2-h post-meal glucose and lipid measurements . RESULTS Mean baseline HbA(1c ) was 8.34 % in the sitagliptin and placebo groups . After 24 weeks , sitagliptin reduced HbA(1c ) by 0.74 % ( p < 0.001 ) relative to placebo . In the subset of patients on glimepiride plus metformin , sitagliptin  reduced HbA(1c ) by 0.89 % relative to placebo , compared with a reduction of 0.57 % in the subset of patients on glimepiride alone . The addition of sitagliptin reduced FPG by 20.1 mg/dl ( p < 0.001 ) and increased homeostasis model assessment -beta , a marker of beta-cell function , by 12 % ( p < 0.05 ) relative to placebo . In patients who underwent a meal tolerance test ( n = 134 ) , sitagliptin decreased 2-h post-pr and ial glucose ( PPG ) by 36.1 mg/dl ( p < 0.001 ) relative to placebo . The addition of sitagliptin was generally well tolerated , although there was a higher incidence of overall ( 60 vs. 47 % ) and drug-related adverse experiences ( AEs ) ( 15 vs. 7 % ) in the sitagliptin group than in the placebo group . This was largely because of a higher incidence of hypoglycaemia AEs ( 12 vs. 2 % , respectively ) in the sitagliptin group compared with the placebo group . Body weight modestly increased with sitagliptin relative to placebo ( + 0.8 vs. -0.4 kg ; p < 0.001 ) . CONCLUSIONS Sitagliptin 100 mg once daily significantly improved glycaemic control and beta-cell function in patients with type 2 diabetes who had inadequate glycaemic control with glimepiride or glimepiride plus metformin therapy . The addition of sitagliptin was generally well tolerated , with a modest increase in hypoglycaemia and body weight , consistent with glimepiride therapy and the observed degree of glycaemic improvement Abstract Objective : The objective was to assess the relative risk ( RR ) for cardiovascular ( CV ) events across all 8 r and omized phase 2/3 trials evaluating saxagliptin in patients with type 2 diabetes mellitus . Methods : Cardiovascular events ( death , myocardial infa rct ion [ MI ] , stroke , revascularization procedures , and cardiac ischemia ) were reported by investigators through st and ard adverse event reporting procedures and were systematic ally identified . Post hoc blinded adjudication of all deaths , MIs , and strokes was performed using prespecified endpoint definitions by an independent clinical events committee ( CEC ) . Results : A total of 4607 r and omized and treated patients ( n = 3356 treated with saxagliptin [ 2.5–100 mg/d ] ; n = 1251 , comparator [ n =  
    Output:
    
Saxagliptin , used as monotherapy and in combination regimens , has been associated with significant reductions in HbA(1c ) and significant increases in the rate of achieving target HbA(1c )  in patients with T2DM .
It has been reported to be well tolerated compared with other oral antihyperglycemic agents .
Based on the findings from the studies in this review , the primary role of saxagliptin is expected to be in combination therapy with other antihyperglycemic agents