***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: BACKGROUND Improved blood-glucose control decreases the progression of diabetic microvascular disease , but the effect on macrovascular complications is unknown . There is concern that sulphonylureas may increase cardiovascular mortality in patients with type 2 diabetes and that high insulin concentrations may enhance atheroma formation . We compared the effects of intensive blood-glucose control with either sulphonylurea or insulin and conventional treatment on the risk of microvascular and macrovascular complications in patients with type 2 diabetes in a r and omised controlled trial . METHODS 3867 newly diagnosed patients with type 2 diabetes , median age 54 years ( IQR 48 - 60 years ) , who after 3 months ' diet treatment had a mean of two fasting plasma glucose ( FPG ) concentrations of 6.1 - 15.0 mmol/L were r and omly assigned intensive policy with a sulphonylurea ( chlorpropamide , glibenclamide , or glipizide ) or with insulin , or conventional policy with diet . The aim in the intensive group was FPG less than 6 mmol/L. In the conventional group , the aim was the best achievable FPG with diet alone ; drugs were added only if there were hyperglycaemic symptoms or FPG greater than 15 mmol/L. Three aggregate endpoints were used to assess differences between conventional and intensive treatment :  any diabetes-related endpoint ( sudden death , death from hyperglycaemia or hypoglycaemia , fatal or non-fatal myocardial infa rct ion , angina , heart failure , stroke , renal failure , amputation [ of at least one digit ] , vitreous haemorrhage , retinopathy requiring photocoagulation , blindness in one eye , or cataract extraction ) ; diabetes-related death ( death from myocardial infa rct ion , stroke , peripheral vascular disease , renal disease , hyperglycaemia or hypoglycaemia , and sudden death ) ; all-cause mortality . Single clinical endpoints and surrogate sub clinical endpoints were also assessed . All analyses were by intention to treat and frequency of hypoglycaemia was also analysed by actual therapy . FINDINGS Over 10 years , haemoglobin A1c ( HbA1c ) was 7.0 % ( 6.2 - 8.2 ) in the intensive group compared with 7.9 % ( 6.9 - 8.8 ) in the conventional group -- an 11 % reduction . There was no difference in HbA1c among agents in the intensive group . Compared with the conventional group , the risk in the intensive group was 12 % lower ( 95 % CI 1 - 21 , p=0.029 ) for any diabetes-related endpoint ; 10 % lower ( -11 to 27 , p=0.34 ) for any diabetes-related death ; and 6 % lower ( -10 to 20 , p=0.44 ) for all-cause mortality . Most of the risk reduction in the any diabetes-related aggregate endpoint was due to a 25 % risk reduction ( 7 - 40 , p=0.0099 ) in microvascular endpoints , including the need for retinal photocoagulation . There was no difference for any of the three aggregate endpoints between the three intensive agents ( chlorpropamide , glibenclamide , or insulin ) . Patients in the intensive group had more hypoglycaemic episodes than those in the conventional group on both types of analysis ( both p<0.0001 ) . The rates of major hypoglycaemic episodes per year were 0.7 % with conventional treatment , 1.0 % with chlorpropamide , 1.4 % with glibenclamide , and 1.8 % with insulin .  Weight gain was significantly higher in the intensive group ( mean 2.9 kg ) than in the conventional group ( p<0.001 ) , and patients assigned insulin had a greater gain in weight ( 4.0 kg ) than those assigned chlorpropamide ( 2.6 kg ) or glibenclamide ( 1.7 kg ) . INTERPRETATION Intensive blood-glucose control by either sulphonylureas or insulin substantially decreases the risk of microvascular complications , but not macrovascular disease , in patients with type 2 diabetes . ( ABSTRACT TRUNCATED Abstract Objective : We compared the effects of two sulphonylureas , glibenclamide and gliclazide , on ischaemic preconditioning ( IPC ) and nicor and il-induced protection in the in-vivo rat . We also studied the effects of these agents on the membrane potential of isolated rat mitochondria . Methods : Anaesthetised male Sprague-Dawley rats were used in an open chest model of myocardial infa rct ion . Animals were r and omly assigned to receive one of the following drugs : ( 1 ) saline control , ( 2 ) glibenclamide , 0.3 mg/kg , or ( 3 ) gliclazide , 1 mg/kg i.v . bolus . Each was then further r and omised to one of the following treatments : ( a ) control , ( b ) IPC ( consisting of 2 × 5 mins of regional ischaemia and 5 minutes reperfusion ) or ( c ) nicor and il ( 50 ug/kg/min i.v ) . infusion . Each group then underwent 25 mins regional ischaemia and 2 hrs reperfusion . Infa rct to risk zone ratio ( % ) was calculated by computerised planimetry of tetrazolium stained heart slices . The membrane potential of mitochondria isolated from rat ventricles was measured using flow cytometry . Comparisons were made between groups in control medium , nicor and il alone , and nicor and il with either glibenclamide or gliclazide . Results : Infa rct size was significantly reduced with IPC ( 15.0 ± 1.1 % , ) and nicor and il ( 25.5 ± 4.2 % ) , versus control ( 44.1 ± 3.2 % ) , p < 0.005 . Glibenclamide  abolished IPC ( 40.8 ± 4.6 % ) and nicor and il-induced protection completely ( 39.5 ± 5.1 % ) . Gliclazide had no adverse effect on IPC ( 20.4 ± 1.9 % ) or nicor and il-induced protection ( 23.6 ± 2.2 % ) , p < 0.005 . Nicor and il caused a partial depolarisation of the mitochondrial membrane potential ( −14.92 ± 2.34 % ) , which was abolished by glibenclamide ( + 2.03 ± 0.53 % ) , but not gliclazide ( −16.47 ± 3.36 % ) , p < 0.01 . Conclusion : Both IPC and nicor and il-induced protection are abolished by glibenclamide but not gliclazide in-vivo . These results may have important clinical implication s in type II diabetic patients at risk of acute coronary syndromes BACKGROUND Plasma adiponectin levels increase after the administration of glimepiride . This unique effects would also be expected to improve other adipocytokines and have anti-atherosclerotic action in patients with metabolic syndrome . METHODS Thirty-four patients with type 2 diabetes mellitus who were administrated glibenclamide  were r and omly divided into two groups . In 20 patients glibenclamide was changed to glimepiride ( GP group ) , and the administration of glibenclamide ( GB group ) was continued in 14 patients . Twelve patients receiving insulin therapy ( INS group ) were enrolled for comparison . The levels of plasma adiponectin , high sensitive-CRP , TNF-alpha , interleukin-6 , homeostasis model assessment -insulin resistance ( HOMA-IR ) , brachial-ankle pulse wave velocity ( baPWV ) and augmentation index ( AI ) were measured before and 28 weeks after the therapy . RESULTS HOMA-IR in the GP group was significantly decreased compared to the GB group . Plasma adiponectin levels were significantly increased in the GP group but not in the other groups . TNF-alpha , interleukin-6 and high sensitive-CRP levels were significantly decreased in the GP group , but not in the other groups . The baPWV and AI levels did not change in either the GB or the INS group , but were significantly decreased in the GP group . CONCLUSIONS Glimepiride appears to improve insulin resistance and atherosclerotic disorders Our objective was to investigate the effect of rifampin ( INN , rifampicin ) on the pharmacokinetics and pharmacodynamics of gliclazide , a sulfonylurea antidiabetic drug The potential interactions between H2-receptor antagonists , cimetidine and ranitidine , and glibenclamide were studied in 15 non-smoking male volunteers . The study consisted of six treatment phases . Treatment A ( 3 h oral glucose tolerance test ) consisted of 75 g dextrose in 300 ml carbonated water . Treatment B consisted of one 5 mg tablet of glibenclamide in addition to a glucose tolerance test . Treatment C , cimetidine 300 mg orally four times daily for 4 days and Treatment D , ranitidine 150 mg orally twice daily for 4 days were administered in a r and omized , crossover fashion . On day 3 of Treatments C and D , subjects received an oral glucose tolerance test . On day 4 of Treatments C and D , subjects received 5 mg of glibenclamide in addition to cimetidine ( Treatment E ) or ranitidine ( Treatment F ) and an oral glucose tolerance test . Compared with the control treatment , cimetidine increased the  glibenclamide AUC ( 973 vs 710 ng ml-1 h ) , but during ranitidine dosing glibenclamide AUC ( 726 ng ml-1 h ) was not significantly different from the control . Apparent oral glibenclamide clearance decreased from 8.25 l h-1 under the control treatment to 6.0 l h-1 following cimetidine but was unchanged during ranitidine ( 7.97 l h-1 ) . Plasma glucose concentrations were unexpectedly higher when glibenclamide was administered with cimetidine or ranitidine ( glucose AUC 237 mg dl-1 h , 228 mg dl-1 h ) when compared with glibenclamide administered alone ( 195 mg dl-1 h , P less than 0.0001 ) . Plasma insulin concentrations were significantly elevated when H2-receptor antagonists and glibenclamide were administered concurrently . ( ABSTRACT TRUNCATED AT 250 WORDS Background : Sulfonylurea compounds may impair ischemic preconditioning and endogenous fibrinolysis . Increased mortality has been reported in diabetics receiving these drugs prior to admission for acute myocardial infa rct ion when treated by direct angioplasty . Although thrombolytics are currently employed far more frequently than direct angioplasty the effect of sulfonylureas on mortality in the setting of thrombolysis has not been previously addressed . Methods : Two hundred forty five diabetics treated with either accelerated t-PA or streptokinase in a national , multi-center , r and omized comparison of argatroban vs. heparin ( n=1200 ) were grouped by anti-diabetic treatment prior to hospitalization , and their outcomes were compared by retrospective analysis . Results : Baseline characteristics were similar in all groups ( sulfonylureas : n=121 , oral medications other than sulfonylureas : n=17 , insulin : n=28 , diet alone : n=79 ) . Sulfonylurea use was not associated with increased mortality or adverse event rates . By logistic regression analysis with diet treatment as reference , only prior insulin use was associated with higher risk for mortality at 30 days and 1 year ( odds ratios 4.5 and 5.22 , respectively , p<0.05 ) . Conclusions : Sulfonylureas use prior to admission is not associated with adverse outcomes in diabetics treated with thrombolytics for myocardial infa rct ion . Since direct angioplasty may increase mortality in patients taking these drugs , a r and omized trial is needed to specifically compare different strategies of acute reperfusion in diabetics . Abbreviated abstract . Increased mortality has been reported in diabetics using sulfonylureas when treated for myocardial infa rct ion by direct angioplasty . No study has specifically addressed the effect of these drugs on outcomes in the setting of thrombolysis . In a retrospective analysis of 245 diabetics treated with thrombolysis in a r and omized comparison of argatroban vs. heparin , outcomes were compared in relation to anti-diabetic therapy prior to admission . Sulfonyl-urea use did not adversely affect prognosis , which was worst among diabetics previously treated with insulin . In conclusion , sulfonylureas do not worsen outcomes of diabetics treated with current thrombolytic regimens in comparison with other anti-diabetic treatments OBJECTIVE The aim of this study was to examine the relationship between use of metformin and sulfonylurea and mortality in new users of these agents . RESEARCH DESIGN AND METHODS Saskatchewan Health data bases were used to examine population -based mortality rates for new users of oral antidiabetic agents . Individuals with prescriptions for sulfonylurea or metformin in 1991 - 1996 and no use in the year prior were identified as new users . Prescription records were prospect ively followed for 
    Output:
    
The C(SS ) for glimepiride and glyburide ( glibenclamide ) was above IC(50 ) values for all three isoforms , suggesting these drugs are non-selective .
Tolbutamide and repaglinide may have partial pancreatic receptor selectivity because IC(50 ) values for SUR1 and SUR2A/SUR2B overlapped somewhat , with the C(SS ) in the midst of these values .
Insulin secretagogues display different tissue selectivity characteristics at therapeutic doses .
This may translate into different levels of cardiovascular risk