***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: OBJECTIVE To examine whether and how improvement of glycemic control by long-term insulin therapy decreases endothelial activation as measured by serum levels of the soluble adhesion molecules sE-selectin and vascular cell adhesion molecule ( VCAM-1 ) and whether the drug used to lower blood glucose in addition to insulin influences such a response . RESEARCH DESIGN AND METHODS Circulating adhesion molecules were measured before and after 3 and 12 months of therapy in 81 patients with type 2 diabetes and 41 subjects without diabetes . The patients were treated with bedtime administration of NPH insulin combined with either glibenclamide ( n = 19 ) , metformin ( n = 17 ) , glibenclamide and metformin ( n = 17 ) , or morning administration of NPH insulin ( n = 23 ) . RESULTS Before insulin therapy , serum sE-selectin level was 71 % higher in the patients with type 2 diabetes ( 77 + /- 4 ng/ml ) than in the normal subjects ( 45 + /- 3 ng/ml , P < 0.001 ) , whereas levels of sVCAM-1 were comparable ( 420 + /- 25 vs. 400 + /- 11 ng/ml , respectively ) . Glycemic control in all patients improved as judged from a decrease in HbA1c from 9.7 + /- 0.2 to 7.6 + /- 0.1 % ( P < 0.001 ) . sE-selectin decreased to 67 + /- 4 ng/ml by 3 months ( P < 0.001 vs. 0 months ) and then remained unchanged until 12 months ( 70 + /- 4 ng/ml P < 0.001 vs 0 months ) . sVCnM-1 levels at 12 months was similar to those at 0 months ( 416 + /- 25 ng/ml ) . The change in glycemic control , measured by HbA1c , but not in other parameters , was correlated with the change of sE-selectin ( r = 0.41 , P < 0.001 ) within the patients with type 2 diabetes . The decreases in sE-selectin were not different between the various treatment groups . CONCLUSIONS We conclude that improvement in glycemic control by administration of insulin alone or insulin combined with either glibenclamide , metformin , or both agents induces a sustained decrease in sE-selectin , the magnitude of which seems to be dependent on the degree of improvement in glycemia . These data suggest that sE-selectin might provide a marker of effects of treatment of chronic hyperglycemia on endothelial activation 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 We conducted a double-blind crossover study to determine which patient characteristics best predict a beneficial response to combined insulin-glyburide therapy . Glyburide ( 15 mg/day ) or placebo was added to the treatment regimen of 31 insulin-treated type II ( non-insulin-dependent ) diabetic subjects . During glyburide therapy , there was a significant improvement in glycemic control with a reduction in glycosylated hemoglobin from 9.9 ± 1.3 to 9.1 ± 1.3 % ( P < .001 ) . Patients who responded had higher fasting C-peptide levels ( P < .001 ) and shorter duration s of insulin therapy ( P < .01 ) than those who did not respond . Glyburide withdrawal was associated with a > expected deterioration in glycemic control . Patients on insulin therapy for > 8 yr are unlikely to benefit significantly from the addition of glyburide to their treatment regimen To assess the effect of Glipizide on glycaemic control and peripheral insulin sensitivity , 9 type 1 ( insulin dependent ) diabetic patients with normal BMI , mean age 42.1 + /- 11.0 years , diabetes duration 16.3 + /- 9.2 years were studied . They were treated by continuous subcutaneous insulin infusion for a mean duration of 32.2 + /- 11.0 months , they were in good glycaemic control ( mean HbA1 7.9 + /- 1.2 % , upper limit of normal value 7.5 % ) . In a double blind r and omized control study they were successively allocated for a three month period to 15 mg of Glipizide daily or a Placebo . At the end of each period the following parameters were recorded : HbA1 , mean plasma glucose levels , daily insulin dosage : basal rate and pre pr and ial bolus , peripheral insulin sensitivity assessed by euglycaemic hyperinsulinic clamp technique , the addition of Glipizide did not induce any statistically significant modification of HbA1 , glycaemic values , and daily insulin dosage : basal rate 18.2 + /- 8.7 vs. 17.9 + /- 7.3 IU/24 hours and pre pr and ial bolus 18.6 + /- 7.0 vs 17.6 + /- 6.3 IU/24 hours . During the glucose clamp , glucose uptake was similar under Glipizide or Placebo with the 3 levels of insulin infused . These results suggest that in type 1 diabetic patients the addition of Glipizide to insulin therapy does not alter glycaemic control and peripheral insulin sensitivity BACKGROUND Sulfonylurea drugs have been the only oral therapy available for patients with non-insulin-dependent diabetes mellitus ( NIDDM ) in the United States . Recently , however , metformin has been approved for the treatment of NIDDM . METHODS We performed two large , r and omized , parallel-group , double-blind , controlled studies in which metformin or another treatment was given for 29 weeks to moderately obese patients with NIDDM whose diabetes was inadequately controlled by diet ( protocol 1 : metformin vs. placebo ; 289 patients ) , or diet plus glyburide ( protocol 2 :  metformin and glyburide vs. metformin vs. glyburide  ; 632 patients ) . To determine efficacy we measured plasma glucose ( while the patients were fasting and after the oral administration of glucose ) , lactate , lipids , insulin , and glycosylated hemoglobin before , during , and at the end of the study . RESULTS In protocol 1 , at the end of the study the 143 patients in the metformin group , as compared with the 146 patients in the placebo group , had lower mean ( + /- SE ) fasting plasma glucose concentrations ( 189 + /- 5 vs. 244 + /- 6 mg per deciliter [ 10.6 + /- 0.3 vs. 13.7 + /- 0.3 mmol per liter ] , P < 0.001 ) and glycosylated hemoglobin values ( 7.1 + /- 0.1 percent vs. 8.6 + /- 0.2 percent , P < 0.001 ) . In protocol 2 , the 213 patients given metformin and glyburide , as compared with the 210 patients treated with glyburide alone , had lower mean fasting plasma glucose concentrations ( 187 + /- 4 vs. 261 + /- 4 mg per deciliter [ 10.5 + /- 0.2 vs. 14.6 + /- 0.2 mmol per liter ] , P < 0.001 ) and glycosylated hemoglobin values ( 7.1 + /- 0.1 percent vs. 8.7 + /- 0.1 percent , P < 0.001 ) . The effect of metformin alone was similar to that of glyburide alone . Eighteen percent of the patients given metformin and glyburide had symptoms compatible with hypoglycemia , as compared with 3 percent in the glyburide group and 2 percent in the metformin group . In both protocol s the patients given metformin had statistically significant decreases in plasma total and low-density lipoprotein cholesterol and triglyceride concentrations , whereas the values in the respective control groups did not change . There were no significant changes in fasting plasma lactate concentrations in any of the groups . CONCLUSIONS Metformin monotherapy and combination therapy with metformin and sulfonylurea are well tolerated and improve glycemic control and lipid concentrations in patients with NIDDM whose diabetes is poorly controlled with diet or sulfonylurea therapy alone Abstract Objective : To determine the relation between  systolic blood pressure  over time and the risk of macrovascular or microvascular complications in patients with type 2 diabetes . Design : Prospect i ve observational study . Setting : 23 hospital based clinics in Engl and , Scotl and , and Northern Irel and . Participants : 4801 white , Asian Indian , and Afro-Caribbean UKPDS patients , whether r and omised or not to treatment , were included in analyses of incidence ; of these , 3642 were included in analyses of relative risk . Outcome measures : Primary predefined aggregate clinical outcomes : any complications or deaths related to diabetes and all cause mortality . Secondary aggregate outcomes : myocardial infa rct ion , stroke , lower extremity amputation ( including death from peripheral vascular disease ) , and microvascular disease ( predominantly retinal photocoagulation ) . Single end points : non-fatal heart failure and cataract extraction . Risk reduction associated with a 10 mm Hg decrease in up date d mean systolic blood pressure adjusted for specific confounders Results : The incidence of clinical complications was significantly associated with systolic blood pressure , except for cataract extraction . Each 10 mm Hg decrease in up date d mean systolic blood pressure was associated with reductions in risk of 12 % for any complication related to diabetes ( 95 % confidence interval 10 % to 14 % , P<0.0001 ) , 15 % for deaths related to diabetes ( 12 % to 18 % , P<0.0001 ) , 11 % for myocardial infa rct ion ( 7 % to 14 % , P<0.0001 ) , and 13 % for microvascular complications ( 10 % to 16 % , P<0.0001 ) . No threshold of risk was observed for any end point . Conclusions : In patients with type 2 diabetes the risk of diabetic complications was strongly associated with raised blood pressure . Any reduction in blood pressure is likely to reduce the risk of complications , with the lowest risk being in those with systolic blood pressure less than 120 mm Hg OBJECTIVE To assess the efficacy , safety , and dose-response relationship of glimepiride in patients with NIDDM . RESEARCH DESIGN AND METHODS After a 21-day placebo washout period , 304 patients were r and omized to receive either placebo or glimepiride , 1 , 4 , or 8 mg once daily . Fasting plasma glucose ( FPG ) , 2-h postpr and ial glucose ( PPG ) , and HbA1c 
    Output:
    
Higher sulfonylurea doses did not reduce HbA1c more than lower doses .
Conclusions /interpretationSulfonylurea monotherapy lowered HbA1c level more than previously reported , and we found no evidence that increasing sulfonylurea doses result ed in lower HbA1c .
HbA1c is a surrogate endpoint , and we were unable to examine long-term endpoints in these predominately short-term trials , but sulfonylureas appear to be associated with an increased risk of hypoglycaemic events