***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 Background DA-1229 is a novel , potent and selective dipeptidyl peptidase-4 ( DPP-IV ) inhibitor that is orally bioavailable . We aim ed to evaluate the optimal dose , efficacy and safety of DA-1229 , in Korean subjects with type 2 diabetes mellitus suboptimally controlled with diet and exercise . Methods We enrolled 158 patients ( mean age , 53 years and a mean BMI , 25.6 kg/m2 ) . The mean baseline fasting plasma glucose level , HbA1c and duration of diabetes were 8.28 mmol/L , 7.6 % ( 60 mmol/mol ) and 3.9 years , respectively . After 2 or 6 weeks of an exercise and diet program followed by 2 weeks of a placebo period , the subjects were r and omized into one of four groups for a 12-week active treatment period : placebo , 2.5 , 5 or 10 mg of DA-1229 . Results All three doses of DA-1229 significantly reduced HbA1c from baseline compared to the placebo group ( −0.09 in the placebo group vs. −0.56 , −0.66 and −0.61 % in 2.5 , 5 and 10-mg groups , respectively ) but without any significant differences between the doses . Insulin secretory function , as assessed by homeostasis model assessment β-cell , the insulinogenic index , 2-h oral glucose tolerance test ( OGTT ) C-peptide and post-OGTT C-peptide area under the curve (AUC)0–2h , significantly improved with DA-1229 treatment . The incidence of adverse events was similar between the treatment groups and DA-1229 did not affect body weight or induce hypoglycaemic events . Conclusions DA-1229 monotherapy ( 5 mg for 12 weeks ) improved HbA1c , fasting plasma glucose level , OGTT results and β-cell function . This drug was well tolerated in Korean subjects with type 2 diabetes mellitus . © 2014 The Authors . Diabetes/Metabolism Research and Review s published by John Wiley & Sons , Ltd. DA-1229 is a novel , potent and selective DPP-IV inhibitor that is orally bioavailable . In a pharmacodynamic study , more than 80 % of DPP-IV was inhibited by a single dose of 5 mg or higher of DA-1229 , and this level of inhibition was maintained for at least 24 h after a single dose of 10 mg or higher of DA-1229 . This phase II clinical trial was design ed to evaluate the efficacy and safety of oral DA-1229 and to determine the optimal dose to use for a phase III clinical study in Korean subjects with type 2 diabetes 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 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 AIMS This study was conducted to compare the glycaemic efficacy and safety of initial combination therapy with the fixed-dose combination of sitagliptin and metformin versus metformin monotherapy in drug-naive patients with type 2 diabetes . METHODS This double-blind study ( 18-week Phase A and 26-week Phase B ) r and omized 1250 drug-naÏve patients with type 2 diabetes [ mean baseline haemoglobin A1c ( HbA1c ) 9.9 % ] to sitagliptin/metformin 50/500 mg bid or metformin 500 mg bid ( uptitrated over 4 weeks to achieve maximum doses of sitagliptin/metformin 50/1000 mg bid or metformin 1000 bid ) . Results of the primary efficacy endpoint ( mean HbA1c reductions from baseline at the end of Phase A ) are reported herein . RESULTS At week 18 , mean change from baseline HbA1c was -2.4 % for sitagliptin/metformin FDC and -1.8 % for metformin monotherapy ( p < 0.001 ) ; more patients treated with sitagliptin/metformin FDC had an HbA1c value < 7 % ( p < 0.001 ) versus metformin monotherapy . Changes in fasting plasma glucose were significantly greater with sitagliptin/metformin FDC ( -3.8 mmol/l ) versus metformin monotherapy ( -3.0 mmol/l ; p < 0.001 ) . Homeostasis model assessment of β-cell function ( HOMA-β ) and fasting proinsulin/insulin ratio were significantly improved with sitagliptin/metformin FDC versus metformin monotherapy . Baseline body weight was reduced by 1.6 kg in each group . Both treatments were generally well tolerated with a low and similar incidence of hypoglycaemia . Abdominal pain ( 1.1 and 3.9 % ; p = 0.002 ) and diarrhoea ( 12.0 and 16.6 % ; p = 0.021 ) occurred significantly less with sitagliptin/metformin FDC versus metformin monotherapy ; the incidence of nausea and vomiting was similar in both groups . CONCLUSION Compared with metformin monotherapy , initial treatment with sitagliptin/metformin FDC provided superior glycaemic improvement with a similar degree of weight loss and lower incidences of abdominal pain and diarrhoea BACKGROUND Type 2 diabetes mellitus ( T2DM ) is a significant burden in China , where approximately 114 million patients have been diagnosed with diabetes . Chinese patients present with prominent β-cell failure , with result ing deficiency in insulin secretion , particularly early phase insulin secretion leading to postpr and ial hyperglycemia . Sitagliptin , a selective once-daily oral dipeptidyl peptidase-4 inhibitor , has been shown to improve glycemic control as monotherapy and in combination with other antihyperglycemic agents , including sulfonylureas and metformin . METHODS This was a multicenter r and omized double-blind placebo-controlled study conducted in China . The study assessed the safety and efficacy of the addition of sitagliptin 100 mg once daily versus placebo on changes from 
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However , we found no significant improvement in HOMA-IR following treatment with DPP-4 inhibitors as mono-therapy or as add-on therapy .
In conclusion , DPP-4 inhibitors as monotherapy or as add-on therapy significantly improved beta-cell function but had no significant effect on insulin resistance in type 2 diabetes