***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: Aim : To confirm the efficacy of vildagliptin in patients with type 2 diabetes ( T2D ) by testing the hypothesis that glycosylated haemoglobin ( HbA1c ) reduction with vildagliptin is superior to that with voglibose after 12 weeks of treatment . Methods : In this 12-week , r and omized , double-blind , active-controlled , parallel-group study , the efficacy and safety of vildagliptin ( 50 mg bid , n = 188 ) was compared with that of voglibose ( 0.2 mg tid , n = 192 ) in patients with T2D who were inadequately controlled with diet and exercise . Results : The characteristics of two groups were well matched at baseline . The mean age , body mass index ( BMI ) and HbA1c were 59.1 years , 24.9 kg/m2 and 7.6 % , respectively . At baseline , fasting plasma glucose ( FPG ) and 2-h postpr and ial glucose ( PPG ) were 9.01 mmol/l ( 162.2 mg/dl ) and 13.57 mmol/l ( 244.3 mg/dl ) , respectively . The adjusted mean change in HbA1c from baseline to endpoint was −0.95 ± 0.04 % in the vildagliptin-treated patients and −0.38 ± 0.04 % in those receiving voglibose ( between-group change = 0.57 ± 0.06 % , 95 % confidence interval ( CI ) ( −0.68 to −0.46 % ) , p < 0.001 ) , showing that vildagliptin was superior to voglibose . Endpoint HbA1c ≤ 6.5 % was achieved in 51 % vildagliptin-treated patients compared with 24 % patients who were on voglibose ( p < 0.001 ) . Vildagliptin also exhibited significantly ( p < 0.001 ) greater reduction compared with voglibose in both FPG [ 1.34 vs. 0.43 mmol/l ( 24.1 vs. 7.8 mg/dl ) ] and 2-h PPG [ 2.86 vs. 1.1 mmol/l ( 51.5 vs. 19.8 mg/dl ) ] . Overall adverse events ( AEs ) were lower in the vildagliptin-treated patients compared with that in the voglibose-treated patients ( 61.2 vs. 71.4 % ) , with no incidence of hypoglycaemia and serious adverse events with vildagliptin . Gastrointestinal AEs were significantly lower with vildagliptin compared with that of the voglibose ( 18.6 vs. 32.8 % ; p = 0.002 ) . Conclusions : Vildagliptin ( 50 mg bid ) showed superior efficacy and better tolerability compared with voglibose in Japanese patients with T2D 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 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 The aim of the study was to compare the effects of vildagliptin added to pioglitazone or glimepiride on metabolic and insulin resistance related-indices in poorly controlled type 2 diabetic patients ( T2DM ) . 168 patients with T2DM were r and omized to take either pioglitazone 30 mg once a day plus vildagliptin 50 mg twice a day or glimepiride 2 mg 3 times a day plus vildagliptin 50 mg twice a day . We evaluated body weight , body mass index ( BMI ) , glycated hemoglobin ( HbA1c ) , fasting plasma glucose ( FPG ) , postpr and ial plasma glucose ( PPG ) , fasting plasma insulin ( FPI ) , homeostasis model assessment insulin resistance index ( HOMA-IR ) , homeostasis model assessment beta-cell function index ( HOMA-beta ) , fasting plasma proinsulin ( FPPr ) , proinsulin/fasting plasma insulin ratio ( Pr/FPI ratio ) , adiponectin ( ADN ) , resistin ( R ) , tumor necrosis factor-alpha ( TNF-alpha ) , and high sensitivity C-reactive protein ( Hs-CRP ) at their baseline values , and after 3 , 6 , 9 , and 12 months of treatment . We observed a similar improvement of HbA1c , FPG , PPG , and Hs-CRP compared to baseline in the 2 groups . Fasting plasma insulin , FPPr , Pr/FPI ratio , R , and TNF-alpha were significantly decreased and ADN was significantly increased with pioglitazone plus vildagliptin , but not with glimepiride plus vildagliptin .  HOMA-IR , and HOMA-beta values obtained with pioglitazone plus vildagliptin were significantly better than the values obtained with glimepiride plus vildagliptin . Pioglitazone plus vildagliptin were found to be more effective in preserving beta-cell function , and in reducing insulin resistance , and inflammatory state parameters OBJECTIVE To assess the efficacy and tolerability of vildagliptin ( 10 , 25 or 50 mg bid ) in Japanese patients with type 2 diabetes mellitus ( T2DM ) . METHODS This 12-week , multicenter , r and omized , double-blind , placebo-controlled , parallel-group study was performed in 291 patients . The primary assessment was change from baseline to endpoint in HbA1c . RESULTS Baseline HbA1c averaged 7.4 % , and the between-treatment difference ( vildagliptin-placebo ) in the HbA1c adjusted mean change was -0.8 % , -1.0 % and -1.2 % with vildagliptin 10 , 25 and 50 mg bid , respectively ( p<0.001 ) . Relative to baseline , body weight did not change significantly in vildagliptin groups . There was no increase in incidence of adverse events in the vildagliptin groups ( 62.0 % , 62.5 % and 61.8 % , 10 , 25 and 50 mg bid , respectively ) compared to placebo ( 73.6 % ) . No deaths or drug-related serious adverse events were reported . Seven hypoglycemic events were observed ( four events ( n=3 ) , two events ( n=2 ) , and one event ( n=1 ) in the vildagliptin 10 and 50 mg bid , and placebo , respectively ) and none of them were severe or dose related . CONCLUSION Vildagliptin 50 mg bid was considered to be the most effective and well-tolerated dose , and therefore can be considered the recommended clinical dose for Japanese patients with T2DM OBJECTIVE The epidemic of type 2 diabetes ( T2DM ) threatens to become the major public health problem of this century . However , a comprehensive comparison of the long-term effects of medications to treat T2DM has not been conducted . GRADE , a pragmatic , unmasked clinical trial , aims to compare commonly used diabetes medications , when combined with metformin , on glycemia-lowering effectiveness and patient-centered outcomes . RESEARCH DESIGN AND METHODS GRADE was design ed with support from a U34 planning grant from the National Institute of Diabetes and Digestive and Kidney Diseases ( NIDDK ) . The consensus protocol was approved by NIDDK and the GRADE Research Group . Eligibility criteria for the 5,000 metformin-treated subjects include < 5 years ' diabetes duration , ≥30 years of age at time of diagnosis , and baseline hemoglobin A1c ( A1C ) of 6.8–8.5 % ( 51–69 mmol/mol ) . Medications representing four classes ( sulfonylureas , dipeptidyl peptidase 4 inhibitors , glucagon-like peptide 1 receptor agonists , and insulin ) will be r and omly assigned and added to metformin ( minimum – maximum 1,000–2,000 mg/day ) . The primary metabolic outcome is the time to primary failure defined as an A1C ≥7 % ( 53 mmol/mol ) , subsequently confirmed , over an anticipated mean observation period of 4.8 years ( range 4–7 years ) . Other long-term metabolic outcomes include the need for the addition of basal insulin after a confirmed A1C > 7.5 % ( 58 mmol/mol ) and , ultimately , the need to implement an intensive basal/bolus insulin 
    Output:
    
Baseline HbA1c level and fasting glucose explain most of the variance in HbA1c change in response to DPP-4 inhibitors : each increase of 1.0 % units HbA1c provides a 0.4 - 0.5 % units greater fall