***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 
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    ***EXAMPLES*** 
    Input: AIMS Insulin analogues are widely used but few data exist comparing different analogue regimens . We compared two such regimens in type 2 diabetes mellitus ( T2DM ) uncontrolled by oral antidiabetic agents ( OADs ) with or without basal insulin . METHODS In a 26-week multinational , multicentre , r and omized treat-to-target trial , OADs were discontinued and subjects r and omized to analogue basal-bolus therapy ( insulin detemir once daily and insulin aspart mealtimes ) or biphasic insulin aspart 30 ( 30 % rapid-acting insulin aspart ) , twice daily . Insulin was titrated to targets for fasting , predinner and postpr and ial plasma glucose ( PG ) , as appropriate . RESULTS Of 719 subjects , 92 % completed the study ; 58 % achieved haemoglobin fraction A(1c ) ( HbA(1c ) ) < or = 7.0 % , with reductions of 1.56 % ( to 6.96 % ) with basal-bolus therapy and 1.23 % ( to 7.17 % ) with biphasic insulin aspart . Reduction with basal-bolus therapy was superior in the overall population by 0.23 % ( p = 0.0052 ) , with no difference between regimens in insulin-naive patients . Major hypoglycaemia occurred in five basal-bolus patients ( 0.9 % ) and in no patients with biphasic insulin aspart . Incidence of minor hypoglycaemia was similar in both groups . All insulin doses increased during titration , with increase in lunchtime insulin aspart dose and equal distribution of breakfast and dinner biphasic insulin aspart doses . Insulin detemir remained once daily in 87 % of patients . CONCLUSIONS Modern insulin analogue regimens , adjusted to PG targets , enable a majority of people with T2DM to reach HbA(1c ) < or = 7.0 % after failure of OADs and OAD-basal insulin therapy . Insulin-treated patients may benefit more from transfer to analogue basal-bolus therapy , while insulin-naive individuals benefit equally well from the more convenient biphasic analogue regimen OBJECTIVE Safety and efficacy of biphasic insulin aspart 70/30 ( BIAsp 70/30 , prebreakfast and presupper ) were compared with once-daily insulin glargine in type 2 diabetic subjects inadequately controlled on oral antidiabetic drugs ( OADs ) . RESEARCH DESIGN AND METHODS This 28-week parallel-group study r and omized 233 insulin-naive patients with HbA(1c ) values > /=8.0 % on > 1,000 mg/day metformin alone or in combination with other OADs . Metformin was adjusted up to 2,550 mg/day before insulin therapy was initiated with 5 - 6 units BIAsp 70/30 twice daily or 10 - 12 units glargine at bedtime and titrated to target blood glucose ( 80 - 110 mg/dl ) by algorithm-directed titration . RESULTS A total of 209 subjects completed the study . At study end , the mean HbA(1c ) value was lower in the BIAsp 70/30 group than in the glargine group ( 6.91 + /- 1.17 vs. 7.41 + /- 1.24 % , P < 0.01 ) . The HbA(1c ) reduction was greater in the BIAsp 70/30 group than in the glargine group ( -2.79 + /- 0.11 vs. -2.36 + /- 0.11 % , respectively ; P < 0.01 ) , especially for subjects with baseline HbA(1c ) > 8.5 % ( -3.13 + /- 1.63 vs. -2.60 + /- 1.50 % , respectively ; P < 0.05 ) . More BIAsp 70/30-treated subjects reached target HbA(1c ) values than glargine-treated subjects ( HbA(1c ) < /=6.5 % : 42 vs. 28 % , P < 0.05 ; HbA(1c ) < 7.0 % : 66 vs. 40 % , P < 0.001 ) . Minor hypoglycemia ( episodes/year ) was greater in the BIAsp 70/30 group than in the glargine group ( 3.4 + /- 6.6 and 0.7 + /- 2.0 , respectively ; P < 0.05 ) . Weight gain and daily insulin dose at study end were greater for BIAsp 70/30-treated subjects than for glargine-treated subjects ( weight gain : 5.4 + /- 4.8 vs. 3.5 + /- 4.5 kg , P < 0.01 ; insulin dose : 78.5 + /- 39.5 and 51.3 + /- 26.7 units/day , respectively ) . CONCLUSIONS In subjects with type 2 diabetes poorly controlled on OADs , initiating insulin therapy with twice-daily BIAsp 70/30 was more effective in achieving HbA(1c ) targets than once-daily glargine , especially in subjects with HbA(1c ) > 8.5 % BACKGROUND To overcome the complicated mixing procedures required in the use of insulin formulations , premixed formulations consisting of rapid-acting and intermediate-type insulin in various mixing proportions have been developed . Biphasic insulin aspart 50 ( BIAsp50 ) and 30 ( BlAsp30 ) are 2 premixed formulations containing the active ingredient insulin aspart ( IAsp ) and consisting of a rapid-acting component soluble IAsp ) and intermediate-acting component ( protamine-crystallized protracted IAsp ) in ratios of 50/50 and 30/70 , respectively . These formulations are provided with the expectation that BIAsp30 and BIAsp50 will be beneficial for patients needing to improve their postpr and ial blood glucose control without changing their dietary habits and lifestyles . BIAsp30 has been widely used in medical practice , whereas BIAsp50 is being investigated in clinical trials . OBJECTIVE The aim of this study was to compare the pharmacokinetic ( PK ) and pharmacodynamic ( PD ) profiles of BIAsp50 ( test ) and  BIAsp30 ( reference ) after single-dose SC injection in patients with type 2 diabetes mellitus . METHODS This single-center , r and omized , doubleblind , 2-period , crossover trial was conducted at the H.E.C. Science Clinic , Yokohama , Japan . Male and female patients aged > or = 20 years with a > or = 1 year history of type 2 diabetes were eligible . Patients were r and omly assigned to 1 of 2 treatment sequences : group A received BIAsp30 in period 1 and BIAsp50 in period 2 ; group B received BIAsp50 in period 1 and BIAsp30 in period 2 . All treatments were administered as an SC injection of a single dose ( 0.3 U/kg ) . The study periods were separated by a washout period of 4 to 21 days . For PK analysis of IAsp ( maximum serum IAsp concentration [ C(max , IAsp ) ; primary end point ] , AUC of serum IAsp 0 to 120 , 240 , and 480 minutes after administration [ AUC(0 - 120 min , IAspl ) , AUC(0 - 240 min , IAsp ) , and AUC(0 - 480 min , IAsp5 ) respectively ] , and time to ( Cmax , IAsp ) [ T(max , IAsp ) ] ) , blood sample s were drawn immediately before ( baseline ) and at prespecified time points over 480 minutes after administration . The PD profiles of BIAsp50 and BIAsp30 were also examined by comparing the time course of the glucose infusion rate ( GIR ) using the euglycemic clamp technique . The PD end points were AUC of GIR 0 to 120 minutes after administration ( AUC(0 - 120 min , GIR ) ) , maximum GIR ( GIR(max ) ) , and time to GIRmax ( T(max , GIR ) ) . Tolerability was assessed using physical examination , including vital sign measurement , electrocardiography , body weight , adverse events ( AEs ) , and clinical laboratory analysis ( hematology and serum biochemistry ) . RESULTS Six men and 4 women were enrolled in the study ( mean age , 62.4 years ; mean body weight , 58.3 kg ; mean body mass index , 22.22 kg/m(2 ) ; mean duration of diabetes , 9.53 years ; and mean glycosylated hemoglobin concentration , 6.07 % ) . Mean(Cmax , IAsp ) with BIAsp50 was 63 % higher than that for BIAsp30 ( P < 0.002 ) . The BIAsp50/BIAsp30 ratio with AUC(0 - 120 min , IAsp ) was 1.68 ( 95 % CI , 1.31 - 2.14 ) . The BIAsp50/BIAsp30 ratiofor AUC(0 - 120 min , GIR ) was 1.31 ( 95 % CI , 1.02 - 1.68 ) . A total of 9 AEs were reported in 5 patients , but none of the AEs were considered related to the study drug . CONCLUSION In this small PK/PD study in adults with type 2 diabetes in Japan , mean C(max , IAsp ) was significantly higher with BIAsp50 than with BIAsp30 , and AUC(0 - 120 min , IAsp ) and AUC(0 - 120 min , GIR ) were higher with BIAsp50 than with BIAsp30 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 
    Output:
    
These studies suggest that premixed insulin analogues are equally or more effective in reducing A1C compared to basal insulin analogues alone in spite of the small increase in the risk of nonsevere hypoglycemic events and non clinical ly significant weight gain .
Premixed insulin analogues can be used in insulin-naïve patients , in patients already on basal insulin therapy , and those using basal-bolus therapy who are noncompliant with blood glucose self-monitoring and titration of multiple insulin doses .