***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: OBJECTIVE Hypoglycemia is associated with serious health outcomes for patients treated for diabetes . However , the outcome of out patients with type 2 diabetes who have experienced hypoglycemia episodes is largely unknown . RESEARCH DESIGN AND METHODS The study population , derived from the National Health Insurance Research Data base released by the Taiwan National Health Research Institutes during 1998–2009 , comprised 77,611 patients with newly diagnosed type 2 diabetes . We design ed a prospect i ve study consisting of r and omly selected hypoglycemic type 2 diabetic patients and matched type 2 diabetic patients without hypoglycemia .  We investigated the relationships of hypoglycemia with total mortality and cardiovascular events , including stroke , coronary heart disease , cardiovascular diseases , and all-cause hospitalization . RESULTS There were 1,844 hypoglycemic events ( 500 in patients and 1,344 out patients ) among the 77,611 patients . Both mild ( outpatient ) and severe ( inpatient ) hypoglycemia cases had a higher percentage of comorbidities , including hypertension , renal diseases , cancer , stroke , and heart disease . In multivariate Cox regression models , including diabetes treatment adjustment , diabetic patients with hypoglycemia had a significantly higher risk of cardiovascular events during clinical treatment periods . After constructing a model adjusted with propensity scores , mild and severe hypoglycemia still demonstrated higher hazard ratios ( HRs ) for cardiovascular diseases ( HR 2.09 [ 95 % CI 1.63–2.67 ] ) , all-cause hospitalization ( 2.51 [ 2.00–3.16 ] ) , and total mortality ( 2.48 [ 1.41–4.38 ] ) . CONCLUSIONS Symptomatic hypoglycemia , whether clinical ly mild or severe , is associated with an increased risk of cardiovascular events , all-cause hospitalization , and all-cause mortality . More attention may be needed for diabetic patients with hypoglycemic episodes 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 The provision of sufficient basal insulin to normalize fasting plasma glucose levels may reduce cardiovascular events , but such a possibility has not been formally tested . METHODS We r and omly assigned 12,537 people ( mean age , 63.5 years ) with cardiovascular risk factors plus impaired fasting glucose , impaired glucose tolerance , or type 2 diabetes to receive insulin glargine ( with a target fasting blood glucose level of ≤95 mg per deciliter [ 5.3 mmol per liter ] ) or st and ard care and to receive n-3 fatty acids or placebo with the use of a 2-by-2 factorial design . The results of the comparison between insulin glargine and st and ard care are reported here . The co primary outcomes were nonfatal myocardial infa rct ion , nonfatal stroke , or death from cardiovascular causes and these events plus revascularization or hospitalization for heart failure . Microvascular outcomes , incident diabetes , hypoglycemia , weight , and cancers were also compared between groups . RESULTS The median follow-up was 6.2 years ( interquartile range , 5.8 to 6.7 ) . Rates of incident cardiovascular outcomes were similar in the insulin-glargine and st and ard-care groups : 2.94 and 2.85 per 100 person-years , respectively , for the first co primary outcome ( hazard ratio , 1.02 ; 95 % confidence interval [ CI ] , 0.94 to 1.11 ; P=0.63 ) and 5.52 and 5.28 per 100 person-years , respectively , for the second co primary outcome ( hazard ratio , 1.04 ; 95 % CI , 0.97 to 1.11 ; P=0.27 ) . New diabetes was diagnosed approximately 3 months after therapy was stopped among 30 % versus 35 % of 1456 participants without baseline diabetes ( odds ratio , 0.80 ; 95 % CI , 0.64 to 1.00 ; P=0.05 ) . Rates of severe hypoglycemia were 1.00 versus 0.31 per 100 person-years . Median weight increased by 1.6 kg in the insulin-glargine group and fell by 0.5 kg in the st and ard-care group . There was no significant difference in cancers ( hazard ratio , 1.00 ; 95 % CI , 0.88 to 1.13 ; P=0.97 ) . CONCLUSIONS When used to target normal fasting plasma glucose levels for more than 6 years , insulin glargine had a neutral effect on cardiovascular outcomes and cancers . Although it reduced new-onset diabetes , insulin glargine also increased hypoglycemia and modestly increased weight . ( Funded by Sanofi ; ORIGIN Clinical Trials.gov number , NCT00069784 . ) 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 Aims /hypothesisIn type 2 diabetic patients we compared 9 months of combination therapy with insulin glargine and metformin with 9 months of NPH insulin combined with metformin . The primary focus was changes in HbA1c ; secondary focus was diurnal glucose profiles and symptomatic hypoglycaemia . Methods In this investigator-initiated open , parallel-group clinical trial involving seven centres , 110 insulin-naive type 2 diabetic patients with poor glycaemic control ( HbA1c ≥8.0 % ) on oral hypoglycaemic agents ( 90 % using sulfonylurea plus metformin )  were r and omised to receive bedtime insulin glargine with metformin ( G+MET ) or bedtime NPH with metformin ( NPH+MET ) for 36 weeks . The patients were taught how to self-adjust their insulin dose and use a modem to send the results of home glucose monitoring to treatment centres . The goal was to achieve a fasting plasma glucose ( FPG ) of 4.0 to 5.5 mmol/l in both groups . Results During the last 12 weeks , FPGs averaged 5.75±0.02 and 5.96±0.03 mmol/l ( p<0.001 ) and insulin doses were 68±5 and 70±6 IU/day ( 0.69±0.05 and 0.66±0.04 IU kg–1 day–1 , NS ) in the G+MET and NPH+MET groups , respectively . At 36 weeks , mean HbA1c was 7.14±0.12 and 7.16±0.14 % , respectively ( NS ) . Symptomatic , but not confirmed symptomatic , hypoglycaemia was significantly lower during the first 12 weeks in the G+MET group ( 4.1±0.8 episodes/patient-year ) than in the NPH+MET group ( 9.0±2.3 episodes/patient-year , p<0.05 ) , but not significantly different thereafter . Glucose levels before dinner were higher in the NPH+MET group ( 10.1±0.3 mmol/l ) than in the G+MET group ( 8.6±0.3 mmol/l , p=0.002 ) throughout the 36-week study . With regard to baseline characteristics such as initial glycaemia or C-peptide , there was no difference between patients who achieved good glycaemic control ( HbA1c < 7.0 % ) and those who did not . Differences were seen in the following : between study centres , weight gain during the run-in period and insulin therapy , and FPG during the last 12 weeks ( 5.7±0.2 vs 6.7±0.3 mmol/l for patients reaching vs those not reaching target , p<0.01 ) . 
    Output:
    
Conclusion For the majority of examined efficacy and safety outcomes , IGlar use in T2DM patients was superior or non-inferior to the alternative insulin treatment options