***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 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 ) 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 the open‐label period through to week 52 . There were no differences between treatment groups in the incidence of adverse events ( AEs ) , including hypoglycemia and predefined gastrointestinal AEs ( nausea , vomiting and diarrhea ) during the double‐blind period , with similar findings in the open‐label period . Conclusions Over a period of 52 weeks , the addition of sitagliptin once‐daily to ongoing metformin therapy was efficacious and generally well tolerated in Japanese patients with type 2 diabetes . This trial was registered with Clinical Trials.gov ( no. NCT00363948 ) Background To compare the safety and efficacy of saxagliptin 2.5 mg twice daily ( BID ) versus placebo add-on therapy to metformin immediate release ( IR ) in patients with type 2 diabetes and inadequate glycemic control with metformin alone . Methods This multicenter , 12-week , double-blind , parallel-group trial enrolled adult out patients with type 2 diabetes ( glycated hemoglobin [ HbA1c ] 7.0%–10.0 % ) on stable metformin IR monotherapy ( ≥1500 mg , BID for ≥8 weeks ) . Patients were r and omized to double-blind saxagliptin 2.5 mg BID or placebo added on to metformin IR following a 2-week , single-blind , placebo add-on therapy lead-in period . The primary end point was the change from baseline to week 12 in HbA1c . Key secondary end points included change from baseline to week 12 in fasting plasma glucose ( FPG ) and the proportion of patients achieving HbA1c < 7.0 % or HbA1c ≤ 6.5 % at week 12 . Efficacy was analyzed in all patients who received r and omized study drug with ≥1 postbaseline assessment . Safety was assessed in all treated patients . Results In total , 74 patients were r and omized to double-blind saxagliptin add-on therapy and 86 to placebo add-on therapy . At week 12 , 
    Output:
    
Additionally , studies in Asian subjects , studies in Japanese subjects , and studies conducted in Japan showed relations when three classifications regarding ethnicity and study regions were applied .