***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 To evaluate the long-term durability of the efficacy of alogliptin compared with glipizide in combination with metformin in people with type 2 diabetes inadequately controlled on stable-dose metformin . METHODS This multicentre , double-blind , active-controlled study r and omized 2639 patients aged 18 - 80 years to 104 weeks of treatment with metformin in addition  to alogliptin 12.5 mg once daily ( n = 880 ) , alogliptin 25 mg once daily ( n = 885 ) or glipizide 5 mg once daily , titrated to a maximum of 20 mg ( n = 874 ) . The primary endpoint was least square mean change from baseline in HbA1c level at 104 weeks . RESULTS The mean patient age was 55.4 years , the mean diabetes duration was 5.5 years and the mean baseline HbA1c was 7.6 % .  HbA1c reductions at week 104 were -0.68 % , -0.72 % and -0.59 % for alogliptin 12.5 and 25 mg and glipizide , respectively [ both doses met the criteria for non-inferiority to glipizide ( p<0.001 ) ; alogliptin 25 mg met superiority criteria ( p=0.010 ) ] . Fasting plasma glucose concentration decreased by 0.05 and 0.18 mmol/l for alogliptin 12.5 and 25 mg , respectively , and increased by 0.30 mmol/l for glipizide ( p < 0.001 for both comparisons with glipizide ) . Mean weight changes were -0.68 , -0.89 and 0.95 kg for alogliptin 12.5 and 25 mg and glipizide , respectively ( p < 0.001 for both comparisons with glipizide ) . Hypoglycaemia occurred in 23.2 % of patients in the glipizide group vs. 2.5 and 1.4 % of patients in the alogliptin 12.5 and 25 mg groups , respectively . Pancreatitis occurred in one patient in the alogliptin 25 mg group and three in the glipizide group . CONCLUSIONS Alogliptin efficacy was sustained over 2 years in patients with inadequate glycaemic control on metformin alone Aims : Most treatments for type 2 diabetes  fail over time , necessitating combination therapy . We investigated the safety , tolerability and efficacy of liraglutide monotherapy compared with glimepiride monotherapy over 2 years Background In a previous pooled analysis of 12 double-blind clinical studies that included data on 6,139 patients with type 2 diabetes , treatment with sitagliptin  , a dipeptidyl peptidase-4 ( DPP-4 ) inhibitor , was shown to be generally well tolerated compared with treatment with control agents . As clinical development of sitagliptin continues , additional studies have been completed , and more patients have been exposed to sitagliptin . The purpose of the present analysis is to up date the safety and tolerability assessment of sitagliptin by pooling data from 19 double-blind clinical studies . Methods The present analysis included data from 10,246 patients with type 2 diabetes who received either sitagliptin 100 mg/day ( N = 5,429 ; sitagliptin group ) or a comparator agent ( placebo or an active comparator ) ( N = 4,817 ; non-exposed group ) . The 19 studies from which this pooled population was drawn represent the double-blind , r and omized studies that included patients treated with the usual clinical dose of sitagliptin ( 100 mg/day ) for between 12 weeks and 2 years and for which results were available as of July 2009 . These 19 studies assessed sitagliptin taken as monotherapy , initial combination therapy with metformin or pioglitazone , or as add-on combination therapy with other antihyperglycemic agents ( metformin , pioglitazone , a sulfonylurea ± metformin , insulin ± metformin , or rosiglitazone + metformin ) . Patients in the non-exposed group were taking placebo , metformin , pioglitazone , a sulfonylurea ± metformin , insulin ± metformin , or rosiglitazone + metformin . The analysis used patient-level data from each study to evaluate between-group differences in the exposure-adjusted incidence rates of adverse events . Results Summary measures of overall adverse events were similar in the sitagliptin and non-exposed groups , except for an increased incidence of drug-related adverse events in the non-exposed group . Incidence rates of specific adverse events were also generally similar between the two groups , except for increased incidence rates of hypoglycemia , related to the greater use of a sulfonylurea , and diarrhea , related to the greater use of metformin , in the non-exposed group and constipation in the sitagliptin group . Treatment with sitagliptin was not associated with an increased risk of major adverse cardiovascular events . Conclusions In this up date d pooled safety analysis of data from 10,246 patients with type 2 diabetes  , sitagliptin 100 mg/day was generally well tolerated in clinical trials of up to 2 years in duration 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 OBJECTIVE —The efficacy and safety of adding liraglutide ( a glucagon-like peptide-1 receptor agonist ) to metformin were compared with addition of placebo or glimepiride to metformin in subjects previously treated with oral antidiabetes ( OAD ) therapy . RESEARCH DESIGN AND METHODS —In this 26-week , double-blind , double-dummy , placebo- and active-controlled , parallel-group trial , 1,091 subjects were r and omly assigned ( 2:2:2:1:2 ) to once-daily liraglutide ( either 0.6 , 1.2 , or 1.8 mg/day injected subcutaneously ) , to placebo , or to glimepiride ( 4 mg once daily ) . All treatments were in combination therapy with metformin ( 1 g twice daily ) . Enrolled subjects ( aged 25–79 years ) had type 2 diabetes , A1C of 7–11 % ( previous OAD monotherapy for ≥3 months ) or 7–10 % ( previous OAD combination therapy for ≥3 months ) , and BMI ≤40 kg/m2 .  RESULTS —A1C values were significantly reduced in all liraglutide groups versus the placebo group ( P < 0.0001 ) with mean decreases of 1.0 % for 1.8 mg liraglutide , 1.2 mg liraglutide , and glimepiride and 0.7 % for 0.6 mg liraglutide and an increase of 0.1 % for placebo . Body weight decreased in all liraglutide groups ( 1.8–2.8 kg ) compared with an increase in the glimepiride group ( 1.0 kg ; P < 0.0001 ) . The incidence of minor hypoglycemia  with liraglutide ( ∼3 % ) was comparable to that with placebo but less than that with glimepiride ( 17 % ; P < 0.001 ) . Nausea was reported by 11–19 % of the liraglutide-treated subjects versus 3–4 % in the placebo and glimepiride groups . The incidence of nausea declined over time . CONCLUSIONS —In subjects with type 2 diabetes , once-daily liraglutide induced similar glycemic control , reduced body weight , and lowered the occurrence of hypoglycemia compared with glimepiride , when both had background therapy of metformin AIMS To assess the efficacy and safety of adjunctive saxagliptin vs glimepiride in elderly patients with type 2 diabetes ( T2D ) and inadequate glycaemic control . METHODS In this multinational , r and omized , double-blind , phase IIIb/IV study ( GENERATION ; NCT01006603 ) , patients aged ≥65 years were r and omized ( 1 : 1 ) to receive saxagliptin 5 mg/day or glimepiride ≤6 mg/day , added to metformin , during a 52-week treatment period . The primary endpoint was achievement of glycated haemoglobin ( HbA1c ) < 7.0 % at week 52 without confirmed/severe hypoglycaemia . The key secondary endpoint was incidence of confirmed/severe hypoglycaemia . Safety and tolerability were also assessed . RESULTS Of 720 patients r and omized ( 360 in each treatment group ; mean age 72.6 years ; mean T2D duration 7.6 years ) , 574 ( 79.8 % ) completed the study  ( saxagliptin 80.3 % ; glimepiride 79.2 % ) . Similar proportions of patients achieved the primary endpoint with saxagliptin and glimepiride ( 37.9 vs 38.2 % ; odds ratio 0.99 , 95 % confidence interval 0.73 , 1.34 ; p = 0.9415 ) ; however , a significant treatment-by-age interaction effect was detected ( p = 0.0389 ) : saxagliptin was numerically ( but not significantly ) superior to glimepiride for patients aged < 75 years ( 39.2 vs 33.3 % ) and numerically inferior for patients aged ≥75 years ( 35.9 vs 45.5 % ) . The incidence of confirmed/severe hypoglycaemia was lower with saxagliptin vs glimepiride ( 1.1 vs 15.3 % ; nominal p < 0.0001 ) . Saxagliptin was generally well tolerated , with similar incidences of adverse events compared with glimepiride . CONCLUSION As avoiding hypoglycaemia is a key clinical objective in elderly patients , saxagliptin is a suitable alternative to glimepiride in patients with T2D aged ≥65 years AIM To compare the long-term safety , tolerability and efficacy of saxagliptin vs. glipizide as add-on therapy to metformin . METHODS Adults with glycated haemoglobin ( HbA1c ) > 6.5 - 10 % ( on stable metformin ≥ 1500 mg/day ) were r and omised to saxagliptin 5 mg/day ( n = 428 ) or glipizide titrated from 5 to 20 mg/day ( mean dose 15 mg/day ; n = 430 ) for 52 weeks with a 52-week extension ( NCT00575588 ) . Assessment of the long-term safety , tolerability and efficacy of add-on saxagliptin vs. glipizide after 104 weeks was a tertiary objective of the initial 52-week study . RESULTS 
    Output:
    
These results suggested that patients with T2DM receiving long-term incretin-based therapies  have a lower risk of MI than do those receiving sulfonylurea-based therapy .