***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: Abbreviations ACCORD Action to Control Cardiovascular Risk in Diabetes ADVANCE Action in Diabetes and Vascular Disease : Preterax and Diamicron Modified-Release Controlled Evaluation AGI α-Glucosidase inhibitor  CAD Coronary artery disease CKD Chronic kidney disease CVD Cardiovascular disease DPP-4 Dipeptidyl peptidase IV GIP Glucose-dependent insulinotropic peptide GLP-1 Glucagon-like peptide 1 NPH Neutral protamine Hagedorn TZD Thiazolidinedione UKPDS UK Prospect i ve Diabetes Study VADT Veterans Affairs Diabetes THE CENTRAL THEME OF THE INSTITUTE OF MEDICINE report on the US drug safety system was the need for a life cycle approach to drug evaluation : both the benefits and the risks need to be evaluated and integrated during the entire market life of a drug . The Food and Drug Administration Amendments Act of 2007 also called on the agency to improve its methods of communicating risks and benefits to patients and physicians . The Institute of Medicine recommendation to “ develop and continually improve a systematic approach to risk-benefit analysis for use throughout the [ Food and Drug Administration ] in the preapproval and postapproval setting s ” specifically acknowledges the need for and the challenges of the development of new methods of combining evidence about risks and benefits . Information that combines the best evidence on benefits with the best data on risks is also needed for daily clinical practice . Whenever a patient and physician decide on a particular course of treatment , they do so because they expect that the likely benefits will exceed potential harms . For the benefits of drug treatments , they often have authoritative sources to provide information : r and omized trials and systematic review s and meta-analyses of such trials . For adverse effects , the situation is different . Given the average duration of r and omized trials ( often months to 1 or 2 years ) and the average number of patients in r and omized trials ( often dozens to a few hundred ) , such trials are at most able to detect and quantify frequent adverse events that occur only early during treatment . Moreover , the adverse effect has to be known beforeh and or anticipated to be recorded systematic ally in the trials . The study population in trials , which often includes young persons with a single diagnosis and without concurrent disease , is often not representative of those who will eventually use the drug in the community . The situation does not much improve in meta- analysis : the typical meta- analysis of r and omized trials covers 1000 to 2500 individuals , only half of whom will have taken the new drug . The sample size precludes good quantification of adverse effects unless they occur at least with a frequency of about 1 per 200 person-years . Meta-analyses of trials do not solve the problem of late adverse effects or the problem of the narrow population included in the trials . The information on harms from trials is incomplete , and the possibility of using and combining such information across trials in systematic review s is limited . Thus , to underst and the full spectrum of adverse effects — those that occur late , that were not known beforeh and , and that are rare but nevertheless serious— and to be able to investigate the true incidence of known adverse effects in circumstances of actual prescribing , well- design ed observational studies will always be necessary . It follows that systematic review s of drug treatments must include not only the results of r and omized trials on benefits but also evidence from observational research on harms . Although the idea to turn to observational data for evidence may be a surprise , the idea makes sense in view of what r and omization does and what r and omized trials are good at doing . R and omized trials are uniquely superior to evaluate the benefits , the intended or hoped-for effects of treatments . The r and om allocation mechanism is able to overcome the strong tendency of physicians to selectively prescribe treatments based on the perceived prognosis and likely outcomes of patients . Although prescriptions that are tailored to individual prognoses constitute desired medical practice , this effort also makes it difficult to compare the benefits of different treatments because patients who receive different treatments will have different prognoses , called “ confounding by indication . ” In general , data from routine daily practice can therefore not be used to assess the benefits of treatment , especially for the comparison between users and nonusers of a drug Summary Aim : To compare the effect of acarbose and gliclazide on clinical findings , biochemical parameters and safety in type 2 diabetic patients insufficiently controlled with medical nutrition therapy ( MNT ) .  Methods : Seventy-two patients ( age 35–70 years , BMI ≤ 35 kg/m2 ) , who had not taken any oral antidiabetic drug previously , were r and omised into two groups after a four-week placebo period , and treated for 24 weeks with acarbose ( 100 mg two to three times daily ) and gliclazide ( 40–80 mg twice daily ) . The study was open and 57 patients ( 33 males and 24 females ) completed it . MNT was provided for each patient based on personal requirements as defined by a dietitian . The effect of treatment was evaluated by fasting and postpr and ial ( PP ) metabolic parameters ( blood glucose , insulin and C peptide levels ) , HbA1C and plasma lipid levels . In addition , side-effects were recorded and clinical examinations performed . Results : Both drugs were effective in reducing of HbA1C , fasting and PP blood glucose levels . However , PP serum insulin levels in the gliclazide group increased more than those in the group treated with acarbose ( p = 0.007 ) . Moreover , a small weight reduction was obtained with acarbose treatment but not with gliclazide . Lipid levels were favourably affected by both drugs . Total cholesterol levels decreased in both groups , the decrease only reaching significance in the acarbose group ( p = 0.013 ) . However , serum levels of LDL cholesterol decreased in both groups ( acarbose and gliclazide , p = 0.033 and p = 0.023 , respectively ) , but the ratio of HDL to LDL cholesterol increased in the acarbose group only ( p = 0.045 ) . Both treatments were generally well tolerated . Common complaints in the acarbose group were flatulence and meteorism ( 29.6 % ) . However , 10.0 % of the patients in the gliclazide group reported at least one mild hypoglycaemic episode . Conclusions : The results of the study demonstrate that acarbose and gliclazide were reasonably effective in improving metabolic control in patients insufficiently controlled with diet alone , and both treatments were well tolerated . Because of its effects on weight reduction and PP hyperinsulinaemia , acarbose may be preferred as a firstline drug , particularly in the treatment of overweight type 2 diabetic patients AIMS This open-label r and omized controlled clinical trial compared the effect on glycaemic control and weight gain of repaglinide vs. gliclazide combined with bedtime NPH insulin in patients with Type 2 diabetes inadequately controlled with oral hypoglycaemic therapy [ HbA1c>7.0 % ( DCCT aligned assay , normal range 4.6 - 6.2 % ) ] . METHODS Eighty subjects with Type 2 diabetes were r and omized to 13 weeks ' open-label treatment with repaglinide 4 mg t.i.d . or gliclazide 160 mg b.i.d . in combination with bedtime NPH insulin ( initial dose 0.5 units/kg ) . The fasting blood glucose ( FBG ) target was < or = 6.0 mmol/l . RESULTS Baseline characteristics were similar for age , sex , weight , BMI , FBG and HbA1c . Glycaemic control improved similarly in both groups-insulin/gliclazide by ( mean ) 1.0 % , from 9.2 to 8.2 % ( P=0.001 ) and by 0.9 % , from 9.4 to 8.5 % in the insulin/repaglinide group ( P=0.005 ) ( P=0.83 between groups ) . Weight gain averaged ( mean + /- sem ) 4.1 + /- 0.5 and 3.4 + /- 0.4 kg in the insulin/gliclazide and insulin/repaglinide groups , respectively ( P<0.0001 for both groups from baseline ) ( P=0.29 between groups ) . The mean number of hypoglycaemic episodes experienced per patient was 2.95 + /- 0.82 ( insulin/gliclazide ) and 2.3 + /- 0.52 ( insulin/repaglinide ) ( P=0.81 between groups ) . Both treatments were associated with significant improvements in Diabetes Treatment Satisfaction [ Diabetes Treatment Satisfaction Question naire-potential range 0 ( min ) to 36 ( max ) ] ; in the insulin/gliclazide group , by 4.9 + /- 1.1 points to 33.3 + /- 0.6 ( P<0.0001 ) and by 3.0 + /- 0.9 points to 34.6 + /- 0.4 ( P=0.0006 ) in the insulin/repaglinide group ( P=0.29 between groups ) . CONCLUSIONS Over 13 weeks , both repaglinide and gliclazide , when combined with bedtime NPH insulin produce similar significant improvements in glycaemic control ( -1 % ) and similar weight gain The objective of this study was to compare the effect of two sulphonylureas on the frequency of hypoglycaemic events and glycaemic control in elderly patients with Type 2 diabetes . Twenty‐two untreated elderly patients were treated with glibenclamide or gliclazide in a r and omized double‐blind fashion . Prior to treatment , a biochemical profile , an oral glucose tolerance test , and a 2‐h hyperglycaemic glucose clamp ( glucose 5.4 mmol I‐zs‐1 above baseline ) were performed . Patients were seen regularly over 6 months to assess glycaemic control and the frequency of hypoglycaemic reactions . Hyperglycaemic clamp studies and oral glucose tolerance tests were repeated at 1 and 6 months . The area under the curve for the oral glucose tolerance test ( glibenclamide : 15.5 ± 0.7 ; gliclazide : 14.9 ± 0.8 mmol I−1 ( ( p = NS ) ) and the haemoglobin A1C  ( glibenclamide : 7.4 ± 0.2 % ; gliclazide : 7.9 ± 0.5 % ( p = NS ) ) were similar at 6 months . Hypoglycaemic reactions were significantly more frequent with glibenclamide than with gliclazide : 17 vs 4 ( p < 0.01 ) . Insulin sensitivity index ( ml kg−1 min−1 pmol −1 × 100 ) was increased significantly by glibenclamide but not gliclazide ( glibenclamide : 0.284 ± 0.116 ( baseline ) vs 0.518 ± 0.102 ( 6 months ) ( p < 0.05 ) , gliclazide : 0.260 ± 0.048 ( baseline ) vs 0.358 ± 0.048 ( 6 months ) ( p = NS ) ) . We conclude that glycaemic control was equivalent with the two drugs but the incidence of hypoglycaemic reactions was significantly greater with glibenclamide probably because this drug increases insulin sensitivity to a greater degree This study has attempted to document a specific haemovascular action of gliclazide on the reversal of early diabetic microangiopathy .  A prospect i ve double-blind controlled study was performed over 2 years , comparing gliclazide versus placebo in insulin-treated and gliclazide  versus glibenclamide  in non-insulin-treated diabetic subjects , after a 1-year run-in period . Glycaemic control was not significantly different in gliclazide- and non-gliclazide-treated subjects before or after the commencement of active therapy . Following treatment with gliclazide in 17/32 insulin-treated and 8/17 non-insulin-treated subjects with Albustix-negative proteinuria , there was no difference in retinopathy score , total proteinuria or the renal clearance of creatinine , albumin , transferrin and immunoglobulin G. In the insulin-treated group , progression of retinopathy was observed in approximately one-third of subjects , but no parameter of proteinuria progressed over 2 years . Thus , this study did not detect a reversal of the parameters measured and does not support an action of gliclazide on  diabetic microangiopathy  , independent of its hypoglycaemic action BACKGROUND Progressive beta-cell failure is a characteristic feature of type 2 diabetes ; consequently , beta-cell secretagogues are useful for achieving sufficient glycaemic control . The European GUIDE study is the first large-scale head-to-head comparison of two sulphonylureas design ed for once-daily administration used under conditions of everyday clinical practice . DESIGN Eight hundred and forty-five type 2 diabetic patients were r and omized to either gliclazide modified release ( MR ) 30 - 120 mg daily or glimepiride 1 - 6 mg daily as monotherapy or in combination with their current treatment ( metformin or an alpha-glucosidase inhibitor ) according to a double-blind , 27-week , parallel-group design . Efficacy was evaluated by HbA1c and safety by hypoglycaemic episodes using the European Agency definition . RESULTS HbA1c decreased similarly in both groups from 8.4 % to 7.2 % 
    Output:
    
The method ological quality of r and omized trials comparing gliclazide to other oral glucose lowering agents was poor and effect estimates on weight were limited by publication bias .
The number of severe hypoglycemic episodes was extremely low , and gliclazide appears at least equally effective compared to other glucose lowering agents .