***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 Abstract Background : The lack of adequate glycaemic control for patients with type 2 diabetes mellitus ( T2DM ) , especially with existing second-line therapies , represents an unmet medical need . Of the newer therapies , the incretin-based medicines , such as saxagliptin , look promising to consoli date second-line pharmacotherapy . Objective : This study evaluates the long-term economic consequences of saxagliptin versus sulfonylurea ( glipizide ) as second-line therapy when used in combination with metformin after failure of monotherapy treatment with metformin , in patients with T2DM in Germany . Methods : A published discrete event simulation model with a fixed-time increment was used to model the effects of different treatment scenarios over a 40-year ( life- ) time horizon . Disease progression was modelled using evidence from the United Kingdom Prospect i ve Diabetes Study ( UKPDS ) 68 . The treatment sequence matched that of published German guidelines , and efficacy and safety data were derived from published sources . The model assumes that quality -adjusted life-years ( QALYs ) are affected by complications , hypoglycaemic events and weight change over a lifetime . Costs were specific to the German setting , where sulfonylureas are generic . Costs and effects were discounted annually at 3 % . The extended perspective of the national sick funds was adopted , and recommendations from the Institute for Quality and Efficiency in Health Care ( IQWiG ) were considered . Results : In the base-case analysis , treatment with saxagliptin plus metformin was associated with a lower incidence of both symptomatic and severe hypoglycaemic events , result ing in an incremental benefit of 0.12 QALYs and an incremental cost-effectiveness ratio ( ICER ) of € 13 931 per QALY gained compared with sulfonylurea plus metformin ( year of costing 2009 ) . Modest reductions in all macro- and microvascular complications were seen in those receiving saxagliptin plus metformin compared with sulfonylurea plus metformin . Sensitivity analysis showed that treatment-related weight changes , as a risk factor for complications , represent the most influential driver of cost effectiveness . Conclusion : The study demonstrated improved outcomes with saxagliptin at a cost that would likely be considered acceptable in the German setting . Furthermore , the findings of the sensitivity analysis suggest that the results are robust to various assumptions concerning input variables and modelling assumptions 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 AIM To assess the efficacy and safety of saxagliptin vs. glipizide as add-on therapy to metformin in patients with type 2 diabetes mellitus and inadequate glycaemic control on metformin alone . METHODS AND PATIENTS A total of 858 patients [ age ≥ 18 years ; glycated haemoglobin ( HbA(1c ) ) > 6.5 - 10.0 % ; on stable metformin doses ≥ 1500 mg/day ] were r and omised 1 : 1 to saxagliptin  5 mg/day or glipizide up-titrated as needed from 5 to 20 mg/day for 52 weeks . The primary objective was to assess if the change from baseline HbA(1c ) achieved with saxagliptin plus metformin was non-inferior to glipizide plus metformin . RESULTS The per- protocol analysis demonstrated non-inferiority of saxagliptin vs. glipizide ; adjusted mean changes from baseline HbA(1c ) were -0.74 % vs. -0.80 % , respectively ; the between-group difference was 0.06 % ( 95 % CI , -0.05 % to 0.16 % ) . Treatment with saxagliptin vs. glipizide was associated with a significantly smaller proportion of patients with hypoglycaemic events ( 3.0 % vs. 36.3 % ; p < 0.0001 ) and a divergent impact on body weight ( adjusted mean change from baseline -1.1 kg with saxagliptin vs. 1.1 kg with glipizide ; p < 0.0001 ) . There was a significantly smaller rise in HbA(1c ) ( % /week ) from week 24 to 52 with saxagliptin vs. glipizide ( 0.001 % vs. 0.004 % ; p = 0.04 ) indicating a sustained glycaemic effect beyond week 24 . Excluding hypoglycaemic events , the proportion of patients experiencing adverse events ( AEs ) was similar ( 60.0 % saxagliptin vs. 56.7 % glipizide ) ; treatment-related AEs were less common with saxagliptin vs. glipizide ( 9.8 % vs. 31.2 % ) , attributable to the higher frequency of hypoglycaemia in glipizide patients . Discontinuation rates result ing from AEs were similar ( ∼4 % ) . CONCLUSION Saxagliptin plus metformin was well tolerated , provided a sustained HbA(1c ) reduction over 52 weeks , and was non-inferior to glipizide plus metformin , with reduced body weight and a significantly lower risk of hypoglycaemia BACKGROUND Severe hypoglycemia may increase the risk of a poor outcome in patients with type 2 diabetes assigned to an intensive glucose-lowering intervention .  We analyzed data from a large study of intensive glucose lowering to explore the relationship between severe hypoglycemia and adverse clinical outcomes . METHODS We examined the associations between severe hypoglycemia and the risks of macrovascular or microvascular events and death among 11,140 patients with type 2 diabetes , using Cox proportional-hazards models with adjustment for covariates measured at baseline and after r and omization . RESULTS During a median follow-up period of 5 years , 231 patients ( 2.1 % ) had at least one severe hypoglycemic episode ; 150 had been assigned to intensive glucose control ( 2.7 % of the 5571 patients in that group ) , and 81 had been assigned to st and ard glucose control ( 1.5 % of the 5569 patients in that group ) . The median times from the onset of severe hypoglycemia to the first major macrovascular event , the first major microvascular event , and death were 1.56 years ( interquartile range , 0.84 to 2.41 ) , 0.99 years ( interquartile range , 0.40 to 2.17 ) , and 1.05 years ( interquartile range , 0.34 to 2.41 ) , respectively . During follow-up , severe hypoglycemia was associated with a significant increase in the adjusted risks of major macrovascular events ( hazard ratio , 2.88 ; 95 % confidence interval [ CI ] , 2.01 to 4.12 ) , major microvascular events ( hazard ratio , 1.81 ; 95 % CI , 1.19 to 2.74 ) , death from a cardiovascular cause ( hazard ratio , 2.68 ; 95 % CI , 1.72 to 4.19 ) , and death from any cause ( hazard ratio , 2.69 ; 95 % CI , 1 
    Output:
    
Conclusions and Implication s of Key Findings This study provides the first systematic evaluation of DPP-4 inhibitors for patients with type 2 diabetes .
It found that , in patients with type 2 diabetes who do not achieve glycemic targets with antidiabetic monotherapy , DPP-4 inhibitors as add-on treatment may represent a cost-effective option compared with sulfonylureas and insulin .