***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: In patients with diabetes and coronary artery disease , the potential negative role of sulfonylurea drugs is under intensive investigation . We assessed the effects of treatment with glibenclamide or insulin on the extension of left ventricular myocardial dysfunction induced by acute ischemia . Nineteen consecutive patients with type 2 diabetes and coronary artery disease entered the study . Each patient was r and omly assigned to either insulin or glibenclamide therapy . Treatment was crossed over after 12 weeks and maintained for another 12 weeks . At the end of each treatment , left ventricular myocardial function at rest and during dipyridamole infusion was studied by  two-dimensional echocardiography under the same conditions of metabolic control . Glibenclamide or insulin treatment did not influence the rest values of left ventricular dimensions , left ventricular ejection fraction ( LVEF ) , or wall motion score index ( WMSI ) . Dipyridamole infusion , in patients receiving glibenclamide treatment , decreased LVEF ( 43 + /- 7 vs. 37 + /- 12 % , P < 0.005 ) and increased WMSI ( 1.4 + /- 0.28 vs. 1.98 + /- 0.24 , P < 0.001 ) compared with baseline values ; during insulin treatment , LVEF ( 46 + /- 8 vs. 45 + /- 11 % , NS ) and WMSI ( 1.4 + /- 0.29 vs. 1.6 + /- 0.4 , NS ) did not change significantly . Peak stress LVEF was higher ( 45 + /- 11 vs. 37 + /- 12 % , P < 0.001 ) and WMSI lower ( 1.6 + /- 0.4 vs. 1.98 + /- 0.24 , P < 0.001 ) in patients receiving insulin . The results indicate that in patients with type 2 diabetes and coronary artery disease , ischemic myocardial dysfunction induced by dipyridamole infusion is less severe during treatment with insulin than with glibenclamide . Restitution of a preconditioning mechanism in insulin-treated patients may be the potential beneficial mechanism CARdiovascular Outcome Trial of LINAgliptin Versus Glimepiride in Type 2 Diabetes ( NCT01243424 ) is an ongoing , r and omized trial in subjects with early type 2 diabetes and increased cardiovascular risk or established complications that will determine the long-term cardiovascular impact of linagliptin versus the sulphonylurea glimepiride .  Eligible patients were sulphonylurea-naïve with HbA1c 6.5%–8.5 % or previously exposed to sulphonylurea ( in monotherapy or in a combination regimen < 5 years ) with HbA1c 6.5%–7.5 % . Primary outcome is time to first occurrence of cardiovascular death , non-fatal myocardial infa rct ion , non-fatal stroke or hospitalization for unstable angina .  A total of 631 patients with primary outcome events will be required to provide 91 % power to demonstrate non-inferiority in cardiovascular safety by comparing the upper limit of the two-sided 95 % confidence interval as being below 1.3 for a given hazard ratio . Hierarchical testing for superiority will follow , and the trial has 80 % power to demonstrate a 20 % relative cardiovascular risk reduction . A total of 6041 patients were treated with median type 2 diabetes duration 6.2 years , 40.0 % female , mean HbA1c 7.2 % , 66 % on 1 and 24 % on 2 glucose-lowering agents and 34.5 % had previous cardiovascular complications . The results of CARdiovascular Outcome Trial of LINAgliptin Versus Glimepiride in Type 2 Diabetes may influence the decision-making process for selecting a second glucose-lowering agent after metformin in type 2 diabetes Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more The publication of the U.K. Prospect i ve Diabetes Study ( UKPDS ) in 1998 helped to shape the management of type 2 diabetes in recent years ( 1 ) . The study demonstrated several points . First , sulfonylureas are as safe as insulin in controlling blood glucose . Second , metformin reduced cardiovascular disease in an overweight subgroup . Third , the same benefit of glycemic control in reducing microvascular disease ( previously noted in type 1 diabetes ) is applied equally to patients with type 2 diabetes . A separation in A1C of ∼1 % in the UKPDS reduced the risk of microvascular disease ( largely diabetic retinopathy ) by ∼25 % . This reflected the data from the Diabetes Control and Complications Trial , where a separation in A1C of 2 % in intensive and st and ard groups led to a reduction in microvascular disease of ∼50 % ( 2 ) . A fourth demonstration was that there was no significant reduction in macrovascular disease but a trend toward fewer myocardial infa rct ions with more intensive glucose control . Fifth , using the current treatment of the time ( first-generation sulfonylureas , human ultratard insulin , or metformin ) , it proved impossible to maintain glucose control , which tended to deteriorate throughout the study . It is now generally believed that the progressive fall in endogenous insulin production as β-cell numbers decline makes it difficult , if not impossible , to maintain tight control using st and ard treatment . Sixth , the UKPDS also showed that in those patients with hypertension , lowering blood pressure ( BP ) to moderate levels with either captopril or atenolol could reduce microvascular disease ( 3 ) . In a subsequent study , the UKPDS investigators presented the rates of both micro- and macrovascular disease according to the achieved levels of A1C during the study ( 4 ) . They showed a linear relationship between A1C and both groups of complications . The implication of the article was that if glycemic control could be tightened below the levels achieved in the UKPDS , then it might be possible to reduce rates , not only of microvascular complications , but also cardiovascular disease as well . The aim of the glucose arm of the Action in Diabetes and Vascular Disease : Preterax and Diamicron MR Controlled Evaluation ( ADVANCE ) trial ( 5 ) was to build on the information gained by the UKPDS and to answer the question as to whether intensifying glucose control to achieve an A1C of < 6.5 % would provide additional benefit in reducing the risk of both micro- and macrovascular disease . ADVANCE also asked questions about BP lowering in patients with type 2 diabetes . The aims of the BP arm were to establish whether routine provision of  BP-lowering therapy  produced additional benefits in terms of macro- and microvascular disease , irrespective of baseline BP , and added to the benefits produced by other cardiovascular preventive therapies , including ACE inhibitors AIMS Hypoglycaemia caused by glucose-lowering therapy has been linked to cardiovascular ( CV ) events . The ORIGIN trial provides an opportunity to further assess this relationship . METHODS AND RESULTS A total of 12 537 participants with dysglycaemia and high CV-risk were r and omized to basal insulin glargine titrated to a fasting glucose of ≤ 5.3 mmol/L ( 95 mg/dL ) or st and ard glycaemic care . Non-severe hypoglycaemia was defined as symptoms confirmed by glucose ≤ 54 mg/dL and severe hypoglycaemia as a requirement for assistance or glucose ≤ 36 mg/dL. Outcomes were : ( i ) the composite of CV death , non-fatal myocardial infa rct ion or stroke ; ( ii ) mortality ; ( iii ) CV mortality ; and ( iv ) arrhythmic death . Hazards were estimated before and after adjustment for a hypoglycaemia propensity score . During a median of 6.2 years ( IQR : 5.8 - 6.7 ) , non-severe hypoglycaemic episodes occurred in 41.7 and 14.4 % glargine and st and ard group participants , respectively , while severe episodes occurred in 5.7 and 1.8 % , respectively . Non-severe hypoglycaemia was not associated with any outcome following adjustment . Conversely , severe hypoglycaemia was associated with a greater risk for the primary outcome ( HR : 1.58 ; 95 % CI : 1.24 - 2.02 , P < 0.001 ) , mortality ( HR : 1.74 ; 95 % CI : 1.39 - 2.19 , P < 0.001 ) , CV death ( HR : 1.71 ; 95 % CI : 1.27 - 2.30 , P < 0.001 ) and arrhythmic death ( HR : 1.77 ; 95 % CI : 1.17 - 2.67 , P = 0.007 ) . Similar findings were noted for severe nocturnal hypoglycaemia for the primary outcome and mortality . The severe hypoglycaemia hazard for all four outcomes was higher with st and ard care than with insulin glargine . CONCLUSION Severe hypoglycaemia is associated with an increased risk for CV outcomes in people at high CV risk and dysglycaemia . Although allocation to insulin glargine vs. st and ard care was associated with an increased risk of severe and non-severe hypoglycaemia , the relative risk of CV outcomes with hypoglycaemia was lower with insulin glargine-based glucose-lowering therapy than with the st and ard glycaemic control . Trial Registration ( ORIGIN Clinical Trials.gov number NCT00069784 ) 
    Output:
    
The present meta- analysis showed an association between SU therapy and a higher risk of major cardiovascular disease-related events compared with other glucose lowering drugs .