***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: OBJECTIVES To compare initiation of insulin therapy by adding once-daily insulin glargine to oral antidiabetic agents ( OADs ) with switching patients to premixed 30 % regular , 70 % human neutral protamine hagedorn insulin ( 70/30 ) without OADs . DESIGN A 24-week , multicenter , open , r and omized ( 1:1 ) , parallel study . SETTING Three hundred sixty-four poorly controlled patients with type 2 diabetes mellitus were treated with once-daily morning insulin glargine with continued OADs ( glimepiride+metformin ) ( glargine+OAD ) or twice-daily 70/30 alone . Insulin dosage in each group was titrated to target fasting blood glucose ( FBG ) of 100 mg/dL or less ( < or=5.6 mmol/L ) using a weekly titration algorithm . PARTICIPANTS This planned subgroup analysis of the original study was based on 130 insulin-naive patients aged 65 and older with FBG of 120 mg/dL or greater ( > or=6.7 mmol/L ) and hemoglobin (Hb)A(1c ) levels between 7.5 % and 10.5 % on OADs ( glargine+OAD , n=67 ; 70/30 , n=63 ) . MEASUREMENTS HbA(1c ) , FBG , hypoglycemia , insulin dose , and adverse events were recorded . RESULTS HbA(1c ) decreased from baseline to endpoint for both glargine+OAD ( from 8.8 % to 7.0 % ) and 70/30 ( from 8.9 % to 7.4 % ) ; adjusted mean HbA(1c ) decrease for glargine+OAD and 70/30 was -1.9 % and -1.4 % , respectively ( P=.003 ) . More patients reached HbA(1c ) of 7.0 % or less without confirmed nocturnal hypoglycemia with glargine+OAD ( n=37 , 55.2 % ) than with 70/30 ( n=19 , 30.2 % ) ( P=.006 ) . FBG decreased significantly more with glargine+OAD ( -57 mg/dL ( -3.2 mmol/L ) ) than with 70/30 ( -40 mg/dL ( -2.2 mmol/L ) ) ( P=.002 ) . Patients treated with glargine+OAD experienced fewer episodes of any hypoglycemia ( 3.68/patient-year ) than did those treated with 70/30 ( 9.09/patient-year ) ( P=.008 ) . CONCLUSION In elderly patients , addition of once-daily morning glargine+OAD is a simple regimen to initiate insulin therapy , restoring glycemic control more effectively and with less hypoglycemia than twice-daily 70/30 alone 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 % OBJECTIVE To determine the safety and efficacy of the long-acting analog insulin glargine compared with NPH insulin in patients with type 2 diabetes who were previously treated with insulin alone . RESEARCH DESIGN AND METHODS A total of 518 subjects with type 2 diabetes who were receiving NPH insulin with or without regular insulin for postpr and ial control were r and omized to receive insulin glargine ( HOE 901 ) once daily ( n = 259 ) or NPH insulin once or twice daily in = 259 ) for 28 weeks in an open-label , multicenter trial . Doses were adjusted to obtain target fasting glucose < 6.7 mmol/l . At study end point , the median total daily insulin dose in both treatment groups was 0.75 IU/kg . RESULTS The treatment groups showed similar improvements in HbA1c from baseline to end point on intent-to-treat analysis . The mean change ( means + /- SD ) in HbA1c from baseline to end point was similar in the insulin glargine group ( -0.41 + /- 0.1 % ) and the NPH group ( -0.59 + /- 0.1 % ) after patients began with an average baseline HbA1c of approximately 8.5 % . The treatments were associated with similar reductions in fasting glucose levels . Overall , mild symptomatic hypoglycemia was similar in insulin glargine subjects ( 61.4 % ) and NPH insulin subjects ( 66.% ) However , nocturnal hypoglycemia in the insulin glargine group was reduced by 25 % during the treatment period after the dose-titration phase(26.5 vs. 35.5 % , P = 0.0136 ) . Subjects in the insulin glargine group experienced less weight gain than those in the NPH group ( 0.4 vs. 1.4 kg , P < 0.0007 ) . CONCLUSIONS In patients with type 2 diabetes , once-daily bedtime insulin glargine is as effective as once- or twice-daily NPH in improving and maintaining glycemic control . In addition , insulin glargine deonstrates a lower risk of nocturnal hypoglycemia and less weight gain compared with NPH insulin AIM To investigate whether the addition of a single bolus of insulin glulisine ( glulisine ) , administered at either breakfast or main mealtime , in combination with basal insulin glargine ( glargine ) and oral antidiabetic drugs ( OADs ) , provides equivalent glycaemic control in patients with type 2 diabetes , irrespective of the time of glulisine injection . METHODS A national , multicentre , r and omized , open-label , parallel-group study of 393 patients with type 2 diabetes who were suboptimally controlled [ haemoglobin A(1c ) ( HbA(1c ) ) > 6.5 - 9.0 % and fasting blood glucose ( BG ) < or=6.7 mmol/l ] on their previous glargine and OAD regimen . A single injection of glulisine was added , either at breakfast or at main mealtime , to their existing therapy . RESULTS The per- protocol group ( n = 316 ) showed improved HbA(1c ) ( baseline vs. end-point ) in the breakfast ( 7.4 vs. 7.0 % ; p < 0.0001 ) and main mealtime groups ( 7.3 vs. 6.9 % ; p < 0.0001 ) . Glulisine given at breakfast was equally effective in controlling HbA(1c ) as glulisine given at the main mealtime [ adjusted HbA(1c ) mean difference ( 95 % confidence interval ) : 0.0481 % ( -0.115 to 0.211 ) ; p < 0.0001 for equivalence ] . Overall , 30.7 % of patients achieved HbA(1c)<or=6.5 % at end-point but slightly more patients met this target in the main mealtime group vs. the breakfast group ( 33.8 vs. 27.8 % ; p = NS ) . This trend continued and was more marked when considering only those patients with HbA(1c ) > 7.0 % at baseline and who reached  HbA(1c)<or=7.0  % at end-point ( 44.1 % overall ) , with 52.2 and 36.5 % for main mealtime and breakfast groups , respectively ( p = 0.028 ) . Most postpr and ial BG values improved within each group , while the number of hypoglycaemias was low and comparable between the two treatment groups . CONCLUSIONS A single bolus of glulisine , added to glargine and OADs , result ed in significantly improved HbA(1c ) levels , irrespective of whether glulisine was administered at breakfast or at main mealtime . These results may represent a simplified and effective approach to treatment intensification in type 2 
    Output:
    
RESULTS Intensity of treatment [ aim of study ( fasting blood glucose , mg/dl ) , dose of insulin , final HbA1c , change of HbA1c and frequency of hypoglycaemia ] was significantly associated with body weight increase , with small differences between basal versus twice-a-day and pr and ial regimen .
At meta- analysis , body weight increase was lower with basal regimen than with twice-a-day regimen and than with a pr and ial regimen .
Within all regimens , body weight increase was lower with detemir than with NPH , with no difference between glargine and NPH ; only two studies directly compared detemir and glargine , indicating lower weight gain with the former insulin .
Within twice-a-day regimens and within pr and ial regimens , comparison was between newer analogues and older drugs , with no significant difference in body weight increase .
CONCLUSION Body weight increase during the first year of insulin treatment is associated with the intensity of treatment ; body weight increase also depends on the insulin regimen applied