***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: Abstract Introduction To assess the efficacy and safety of vildagliptin as add-on therapy in Japanese patients with type 2 diabetes mellitus ( T2DM ) , inadequately controlled on stable long-acting , intermediate-acting , or pre-mixed insulin , with or without concomitant metformin . Methods In this 12-week placebo-controlled study , patients were r and omized to receive either vildagliptin 50 mg twice daily ( bid ) or placebo treatment in a 1:1 ratio . The primary endpoint was change in glycated hemoglobin A1c ( HbA1c ) from baseline to 12-week endpoint . Secondary endpoints included proportion of patients achieving pre-defined HbA1c targets of ≤6.5 % , < 7.0 % , and HbA1c < 7.0 % in patients with baseline HbA1c ≤8.0 % and change in fasting plasma glucose ( FPG ) after 12 weeks of treatment . Regular monitoring was performed to record any treatment-emergent adverse events ( AEs ) and serious adverse events or hypoglycemic episodes . Results Of the 156 patients r and omized , 96.8 % completed the study  ( vildagliptin , n = 76 ; placebo , n = 75 ) . Patient demographics and clinical characteristics were comparable between the groups at baseline . Addition of vildagliptin result ed in statistically significant reductions in HbA1c after 12 weeks ( −1.01 ± 0.06 % ) , with a between-treatment difference of −0.91 ± 0.09 % ( p < 0.001 ) . FPG levels reduced from baseline to 12 weeks in the vildagliptin group ( −1.2 ± 0.2 mmol/L ) , with a between-treatment difference of −1.2 ± 0.3 mmol/L which was significant ( p < 0.001 ) . The proportion of patients achieving HbA1c targets was higher with vildagliptin treatment for all pre-defined responder rate categories . The overall incidence of AEs was comparable between groups ( vildagliptin , 46.2 % vs. placebo , 43.6 % ) . The overall incidence of hypoglycemic events was low and all events were self-treatable without using drug therapy . No severe hypoglycemic events were reported . Conclusion Treatment with vildagliptin 50 mg bid as add-on to insulin with or without metformin result ed in statistically significant reductions in HbA1c in Japanese patients with T2DM . Overall , vildagliptin was well tolerated with a safety profile similar to that of placebo in this patient population . Clinical Trials.gov Identifier , NCT02002221 Funding Novartis Pharma 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 Aims To investigate the efficacy and safety of the dipeptidyl peptidase-4 inhibitor linagliptin in patients with Type 2 diabetes mellitus inadequately controlled by a combination of metformin and pioglitazone . Methods This was a multi-centre , phase 3 , r and omized , double-blind , placebo-controlled study comparing  linagliptin 5 mg once daily ( n = 183 ) and placebo ( n = 89 ) as add-on to metformin and pioglitazone . The primary endpoint was the change from baseline in glycated haemoglobin ( HbA1c ) after 24 weeks . Results The placebo-corrected adjusted mean ( se ) change in HbA1c from baseline to 24 weeks was –6 ( 1 ) mmol/mol [ –0.57 (0.13)% ] ( P < 0.0001 ) . In patients with  baseline HbA1c ≥ 53 mmol/mol ( 7.0 % ) , 32.4 % of patients in the linagliptin group and 13.8 % in the placebo group achieved HbA1c < 53 mmol/mol ( 7.0 % ) ( odds ratio 2.94 ; P = 0.0033 ) . The placebo-corrected adjusted mean ( se ) change from baseline in fasting plasma glucose at week 24 was –0.57 ( 0.26 ) mmol/l [ –10.4 ( 4.7 ) mg/dl ] ( P = 0.0280 ) . The incidence of serious adverse events was 2.2 % with linagliptin and 3.4 % with placebo . Investigator-defined hypoglycaemia occurred in 5.5 % of the linagliptin group and 5.6 % of the placebo group . No meaningful changes in mean body weight were noted for either group . Conclusions Linagliptin as add-on therapy to metformin and pioglitazone produced significant and clinical ly meaningful improvements in glycaemic control , without an additional risk of hypoglycaemia or weight gain ( Clinical Trials Registry No : NCT 00996658 ) 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 Abstract Aims / Introduction The efficacy and safety of sitagliptin , a highly selective dipeptidyl peptidase‐4 inhibitor , when added to metformin monotherapy was examined in Japanese patients with type 2 diabetes . Material s and Methods In this 52‐week , add‐on to metformin study , 149 patients were r and omly assigned to receive sitagliptin 50 mg or placebo once daily in a double‐blind fashion for 12 weeks . Thereafter , all patients who completed the double‐blind period of the study received open‐label sitagliptin 50 mg once daily for 40 weeks , with the investigator option of increasing sitagliptin to 100 mg once daily for patients who met predefined glycemic thresholds . Results After 12 weeks of treatment , the mean change from baseline in glycated hemoglobin ( HbA1c ) significantly decreased with sitagliptin relative to placebo ( between‐group difference [ 95 % confidence interval ] = −0.7 % [ −0.9 to −0.5 ] P < 0.001 ) . At week 12 , the mean changes in 2‐h post‐meal glucose ( −2.6 mmol/L [ −3.5 to −1.7 ] ) and fasting plasma glucose ( −1.0 mmol/L [ −1.3 to −0.6 ] ) also decreased significantly with sitagliptin relative to placebo ( P < 0.001 for both ) . Significant improvements from baseline in glycemic control were also observed in 
    Output:
    
Conclusions The meta- analysis in the article demonstrates that there is statistically significant difference in the HbA1c response in the placebo arm of DPP-4 inhibitor clinical trials conducted in China compared to other countries .