***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: Composite outcomes , in which multiple end points are combined , are frequently used as primary outcome measures in r and omized trials and are often associated with increased statistical efficiency . However , such measures may prove challenging for the interpretation of results . In this article , we examine the use of composite outcomes in major clinical trials , assess the arguments for and against them , and provide guidance on their application and reporting . To assess incidence and quality of reporting , we systematic ally review ed the use of composite end points in clinical trials in Annals of Internal Medicine , BMJ , Circulation , Clinical Infectious Diseases , Journal of the American College of Cardiology , JAMA , Lancet , New Engl and Journal of Medicine , and Stroke from 1997 through 2001 using a sensitive search strategy . We selected for review 167 original reports of r and omized trials ( with a total of 300 276 patients ) that included a composite primary outcome that incorporated all-cause mortality .  Sixty-three trials ( 38 % ) were neutral both for the primary end point and the mortality component . Sixty trials ( 36 % ) reported significant results for the primary outcome measure but not for the mortality component . Only 6 trials ( 4 % ) were significant for the mortality component but not for the primary composite outcome , whereas 19 trials ( 11 % ) were significant for both . Twenty-two trials ( 13 % ) were inadequately reported . Our review suggests that reporting of composite outcomes is generally inadequate , implying that the results apply to the individual components of the composite outcome rather than only to the overall composite . Current guidelines for the undertaking and reporting of clinical trials could be revised to reflect the common use of composite outcomes in clinical trials AIMS The efficacy and safety of the dipeptidyl peptidase-4 inhibitor , linagliptin , added to ongoing metformin therapy , were assessed in patients with Type 2 diabetes who had inadequate glycaemic control ( HbA(1c ) ≥ 7.5 to ≤ 10 % ; ≥ 58.5 to ≤ 85.8 mmol/mol ) with metformin alone . METHODS Patients ( n=333 ) were r and omized to receive double-blind linagliptin ( 1 , 5 or 10 mg once daily ) or placebo or open-label glimepiride ( 1 - 3 mg once daily ) . The primary outcome measure was the change from baseline in HbA(1c ) at week 12 in patients receiving combination therapy compared with metformin alone . RESULTS Twelve weeks of treatment result ed in a mean ( sem ) placebo-corrected lowering in HbA(1c ) levels of 0.40 % ( ± 0.14 ) ; 4.4 mmol/mol ( ± 1.5 ) for 1 mg linagliptin , 0.73 % ( ± 0.14 ) ; 8.0 mmol/mol ( ± 1.5 ) for 5 mg , and 0.67 % ( ± 0.14 ) ; 7.3 mmol/mol ( ± 1.5 ) for 10 mg . Differences between linagliptin and placebo were statistically significant for all doses ( 1 mg , P = 0.01 ; 5 mg and 10 mg , P < 0.0001 ) . The change in mean ( sem ) placebo-corrected HbA(1c ) from baseline was -0.90 % ( ± 0.13 ) ; -9.8 mmol/mol ( ± 1.4 ) for glimepiride . Adjusted and placebo-corrected mean changes in fasting plasma glucose were -1.1 mmol/l for linagliptin 1 mg ( P = 0.002 ) , -1.9 mmol/l for 5 mg and -1.6 mmol/l for 10 mg ( both P < 0.0001 ) . One hundred and six ( 43.1 % ) patients reported adverse events ; the incidence was similar across all five groups . There were no hypoglycaemic events  for linagliptin or placebo , whereas three patients ( 5 % ) receiving glimepiride experienced hypoglycaemia . CONCLUSIONS The addition of linagliptin to ongoing metformin treatment in patients with Type 2 diabetes was well tolerated and result ed in significant and clinical ly relevant improvements in glycaemic control , with 5 mg linagliptin being the most effective dose The objectives of this study were to evaluate the efficacy and tolerability of glimepiride plus extended release metformin ( MET ) on glycemic control in patients with type-2 diabetes mellitus uncontrolled on monotherapy with sulfonylurea or MET . This was a prospect i ve , open-labeled , multicentric study over 12 weeks . Patients who were diagnosed with type-2 diabetes and were uncontrolled on monotherapy with single oral hypoglycemic agents such as glimepiride or MET and characterized by glycosylated hemoglobin ( HbA1c ) ≥7 % and ⩽10 % and fasting plasma glucose ( FPG ) ≥ 140 mg/dL were enrolled in this study . Treatment regimen was started at 1 mg of glimepiride plus 500 mg of MET once a day and was titrated to next dose level depending on the clinician 's judgment , not exceeding a total daily dose of 8 mg of glimepiride and 2000 mg of MET . After 12-weektreatment , glimepiride plus MET combination showed improvement in metabolic control as assessed by changes in HbA1c , FPG , and post pr and ial glucose ( PPG ) . Primary efficacy parameter , HbA1c , was significantly reduced to ( 7.65 ± 1.70 ) at the end of the treatment from the baseline value ( 8.35 ± 0.93 ) ( P < 0.001 ) . Of the patients , 65.79 % showed ≥0.5 % reduction in HbA1c and or HbA1c < 7 % at the end of the therapy . FPG and PPG were significantly reduced at the end of the therapy as compared with baseline values ( P < 0.001 ) . Moreover , the lipid profile was also improved during the treatment period . The addition of glimepiride to MET is an effective treatment for patients inadequately controlled on sulfonylurea or Met alone . A combination of glimepiride with MET achieves good glycemic control with better tolerability profile CONTEXT Although weight reduction is a recommended goal in type 2 diabetes mellitus ( T2DM ) , weight loss is linked to impaired survival in patients with some chronic cardiovascular diseases . OBJECTIVE To assess the association of weight and weight change with mortality and non-fatal cardiovascular outcomes ( hospitalisation , myocardial infa rct ion and stroke ) in T2DM patients with cardiovascular co-morbidity and the effect of pioglitazone-induced weight change on mortality . SETTING AND PARTICIPANTS We assessed in a post hoc analysis body weight and weight change in relation to outcome in 5202 patients from the PROactive trial population who had T2DM and evidence of pre-existing cardiovascular disease . Patients were r and omized to treatment with pioglitazone or placebo in addition to their concomitant glucose-lowering and cardiovascular medication . Mean follow up was 34.5 months . MAIN OUTCOME MEASURE The impact of body weight and body weight change on all-cause mortality , cardiovascular mortality , on non-fatal cardiovascular events and on hospitalisation . RESULTS The lowest mortality was seen in patients with BMI 30 - 35 kg/m(2 ) at baseline . In comparison to this ( reference group ) , patients in the placebo group with BMI < 22 kg/m(2 ) ( Hazard Ratio ( 95 % confidence intervals ) 2.96 [ 1.27 to 6.86 ] ; P=0.012 ) and BMI 22 to 25 kg/m(2 ) ( HR 1.88 [ 1.11 to 3.21 ] ; P=0.019 ) had a higher all-cause mortality . Weight loss was associated with increased total mortality ( HR per 1 % body weight : 1.13 [ 1.11 to 1.16 ] ; P<0.0001 ) , with increased cardiovascular mortality , all-cause hospitalisation and the composite of death , myocardial infa rct ion and stroke . Weight loss of ≥7.5 % body weight ( seen in 18.3 % of patients ) was the strongest cut-point to predict impaired survival ( multivariable adjusted HR 4.42 [ 3.30 to 5.94 ] . Weight gain was not associated with increased mortality . Weight gain in patients treated with pioglitazone ( mean+4.0±6.1 kg ) predicted a better prognosis ( HR per 1 % weight gain : 0.96 [ 0.92 to 1.00 ] P=0.037 ) compared to patients without weight gain . CONCLUSION Among patients with T2DM and cardiovascular co-morbidity , overweight and obese patients had a lower mortality compared to patients with normal weight .  Weight loss  but not  weight gain  was associated with increased mortality and morbidity . There may be an " obesity paradox " in patients with type 2 diabetes and cardiovascular risk . The original PROactive trial is registered as an International St and ard R and omized Controlled Trial ( Number IS RCT N NCT00174993 ) AIM to evaluate the efficacy and safety of adding sitagliptin or glimepiride to the treatment regimen of patients with type 2 diabetes mellitus and inadequate glycaemic control on metformin monotherapy . METHODS patients with type 2 diabetes and an HbA(1c ) of 6.5 - 9.0 % while on a stable dose of metformin ( ≥ 1500 mg/day ) combined with diet and exercise for at least 12 weeks were r and omized in a double-blind manner to receive either sitagliptin 100 mg daily ( N = 516 ) or glimepiride ( starting dose 1 mg/day and up-titrated , based upon patient 's self-monitoring of blood glucose results , to a maximum dose of up to 6 mg/day ) ( N = 519 ) for 30 weeks . The primary analysis assessed whether sitagliptin is non-inferior to glimepiride in reducing HbA(1c ) at week 30 ( based on the criterion of having an upper bound of the 95 % CI less than the prespecified non-inferiority bound of 0.4 % ) . RESULTS the mean baseline HbA(1c ) was 7.5 % in both the sitagliptin group ( n = 443 ) and the glimepiride group ( n = 436 ) . After 30 weeks , the least squares ( LS ) mean change in HbA(1c ) from baseline was -0.47 % with sitagliptin and -0.54 % with glimepiride , with a between-group difference ( 95 % CI ) of 0.07 % ( -0.03 , 0.16 ) . This result met the prespecified criterion for declaring non-inferiority . The percentages of patients with an HbA(1c ) < 7.0 % at week 30 were 52 and 60 % in the sitagliptin and glimepiride groups , respectively . The LS mean change in fasting plasma glucose from baseline ( 95 % CI ) was -0.8 mmol/l ( -1.0 , -0.6 ) with sitagliptin and -1.0 mmol/l ( -1.2 , -0.8 ) with glimepiride , for a between-group difference ( 95 % CI ) of 0.2 mmol/l ( -0.1 , 0.4 ) . The percentages of patients for whom hypoglycaemia was reported were 7 % in the sitagliptin group and 22 % in the glimepiride group ( percentage-point difference = -15 , p < 0.001 ) . Relative to baseline , sitagliptin was associated with a mean weight loss ( -0.8 kg ) , whereas glimepiride was associated with a mean weight gain ( 1.2 kg ) , yielding a between-group difference of -2.0 kg ( p < 0.001 ) . CONCLUSIONS in patients with type 2 diabetes and inadequate glycaemic control on metformin monotherapy , the addition of sitagliptin or glimepiride led to similar improvement in glycaemic control after 30 weeks . Sitagliptin was generally well tolerated . Compared to treatment with glimepiride , treatment with sitagliptin was associated with a lower risk of hypoglycaemia and with weight loss versus weight gain ( Clinical Trials.gov : NCT00701090 ) AIM To assess whether there is a difference in the effects of vildagliptin and glimepiride on glucose fluctuation in patients with type 2 diabetes mellitus ( T2DM ) using continuous glucose monitoring ( CGM ) . METHODS This was an open-label , r and omized cross-over study conducted in T2DM patients . A total of 24 patients ( age : 58.3 ± 5.56 years , baseline HbA1c : 7.6 ± 0.50 % ) who were on stable metformin monotherapy ( 500 - 3000 mg ) were enrolled , 
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The remaining adverse events , including mortality , did not show any differences between both groups .
A greater effectiveness is seen in the glimepiride/metformin association , which should not be diminished by slight differences in adverse effects , with absence of severe hypoglycaemia in over 98 % of patients under treatment .
The association of glimepiride/metformin , both due to cost as well as effectiveness and safety , may be the preferential treatment for most DM2 patients , and it offers a potential advantage in refractory hyperglycemic population s , tolerant to treatment