***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: To compare the efficacy and safety of new insulin glargine 300 U/ml ( Gla‐300 ) with insulin glargine 100 U/ml ( Gla‐100 ) over 12 months of treatment in people with type 2 diabetes using basal insulin and oral antihyperglycaemic drugs ( OADs ) AIM To explore if efficacy and safety findings for insulin glargine 300U/mL ( Gla-300 ) versus insulin glargine 100U/mL ( Gla-100 ) , observed over 6 months in insulin-naïve people with type 2 diabetes , are maintained after 12 months . METHODS EDITION 3 was a phase 3a , r and omized , multicentre , open-label , parallel-group , treat-to-target study of once-daily Gla-300 versus Gla-100 ( target fasting self-monitored plasma glucose , 4.4 - 5.6mmol/L [ 80 - 100mg/dL ] ) . Participants completing the initial 6-month treatment phase continued their previously allocated basal insulin . RESULTS Of 878 participants r and omized , 337/439 ( 77 % ) and 314/439 ( 72 % ) assigned to Gla-300 and Gla-100 , respectively , completed 12 months of treatment . Improved glycaemic control was sustained until 12 months in both treatment groups , with similar reductions in HbA1c from baseline to month 12 ( difference : -0.08 [ 95 % confidence interval ( CI ) : -0.23 to 0.07 ] % or -0.9 [ -2.5 to 0.8 ] mmol/mol ) . Relative risk of experiencing≥1 confirmed ( ≤3.9mmol/L [ ≤70mg/dL ] ) or severe hypoglycaemic event with Gla-300 versus Gla-100 was 0.86 ( 95 % CI : 0.69 to 1.07 ) at night and 0.92 ( 0.82 to 1.03 ) at any time of day . For events with a glycaemic threshold of<3.0mmol/L ( < 54mg/dL ) these numbers were 0.76 ( 0.49 to 1.19 ) and 0.66 ( 0.50 to 0.88 ) . A similar pattern was seen for documented symptomatic events . No between-group differences in adverse events were identified . CONCLUSION Over 12 months , Gla-300 treatment was as effective as Gla-100 in reducing HbA1c in insulin-naïve people with type 2 diabetes , with lower overall risk of hypoglycaemia at the<3.0mmol/L threshold Aims To evaluate the maintenance of efficacy and safety of insulin glargine 300 U/ml ( Gla-300 ) versus glargine 100 U/ml ( Gla-100 ) in people with type 2 diabetes mellitus ( T2DM ) using basal plus meal-time insulin for 12 months in the EDITION 1 trial . Methods EDITION 1 was a multicentre , r and omized , open-label , two-arm , phase IIIa study . Participants completing the initial 6-month treatment period continued to receive Gla-300 or Gla-100 , as previously r and omized , once daily for a further 6-month open-label extension phase . Changes in glycated haemoglobin ( HbA1c ) and fasting plasma glucose concentrations , insulin dose , hypoglycaemic events and body weight were assessed . Results Of 807 participants enrolled in the initial phase , 89 % ( 359/404 ) assigned to Gla-300 and 88 % ( 355/403 ) assigned to Gla-100 completed 12 months . Glycaemic control was sustained in both groups ( mean HbA1c : Gla-300 , 7.24 % ; Gla-100 , 7.42 % ) , with more sustained HbA1c reduction for Gla-300 at 12 months : least squares mean difference Gla-300 vs Gla-100 : HbA1c −0.17 [ 95 % confidence interval ( CI ) −0.30 to −0.05]% . The mean daily basal insulin dose at 12 months was 1.03 U/kg for Gla-300 and 0.90 U/kg for Gla-100 . Lower percentages of participants had ≥1 confirmed [ ≤3.9 mmol/l ( ≤70 mg/dl ) ] or severe hypoglycaemic event with Gla-300 than Gla-100 at any time of day [ 24 h ; 86 vs 92 % ; relative risk 0.94 ( 95 % CI 0.89–0.99 ) ] and during the night [ 54 vs 65 % ; relative risk 0.84 ( 95 % CI 0.75–0.94 ) ] , while the annualized rates of such hypoglycaemic events were similar . No between-treatment differences in adverse events were apparent . Conclusion During 12 months of treatment of T2DM requiring basal and meal-time insulin , glycaemic control was better sustained and fewer individuals reported hypoglycaemia with Gla-300 than with Gla-100 . The mean basal insulin dose was higher with Gla-300 compared with Gla-100 , but total numbers of hypoglycaemic events and overall tolerability did not differ between treatments Abstract Introduction New insulin glargine 300 U mL−1 ( Gla-300 ) is a basal insulin that shows more stable and prolonged pharmacokinetic and pharmacodynamic profiles than insulin glargine 100 U mL−1 ( Gla-100 ) . This study used continuous glucose monitoring ( CGM ) to compare 24-h glucose profiles in a Japanese population using Gla-300 versus Gla-100 . Methods This was an exploratory 8.4-week , single-center , 2-sequence , 2-period , open-label crossover study . Japanese adults with type 1 diabetes mellitus ( T1DM ) treated with basal – bolus insulin , with glycated hemoglobin ( HbA1c ) 6.5–10.0 % and median fasting self-monitored plasma glucose concentration ≤13 mmol L−1 , were r and omized  to Gla-300 followed by Gla-100 ( subgroup 1 ) or vice versa ( subgroup 2 ) , with no washout period . CGM was performed on the last 3 days of the screening period and each treatment period . Primary endpoint was comparison of 24-h glucose variability ( area under the curve [AUC]mean_24 h ) on the second day of each CGM measurement with Gla-300 versus Gla-100 . Baseline and end of treatment period values for HbA1c , fasting plasma glucose ( FPG ) and daily basal/mealtime insulin doses were recorded . Hypoglycemia and adverse events ( AEs ) were recorded . Results Twenty participants were r and omized ( 10 to subgroup 1 and 10 to subgroup 2 ) . Participants showed comparable glucose variability over 24 h ( AUCmean_24 h during treatment with Gla-300 or Gla-100 ( treatment ratio 0.96 ; 90 % confidence interval 0.79 , 1.16 ) . HbA1c and FPG were generally stable across both treatment periods . There was a trend towards fewer participants experiencing ≥1 hypoglycemia event at any time ( 24 h ) and at night ( 00:00–05:59 h ) with Gla-300 versus Gla-100 . Treatment-emergent AEs , reported by 9/20 ( 45 % ) and 4/20 ( 20 % ) participants during Gla-300 and Gla-100 treatment , respectively , were unrelated to study medication . Conclusions In this cohort of Japanese people with T1DM , no between-treatment difference was observed in glucose variability  with Gla-300 versus Gla-100 , as measured by CGM . There was a trend for less hypoglycemia  with Gla-300 , particularly at night , versus Gla-100 . Both treatments were well tolerated . Funding Sanofi , Tokyo , Japan . Clinical trial registration : NCT01676233 , Clinical Trials.gov Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Aims Two single-dose studies were conducted in Japan and Europe to compare the pharmacokinetic ( PK ) and pharmacodynamic ( PD ) profiles of new insulin glargine 300 U/ml ( Gla-300 ) and insulin glargine 100 U/ml ( Gla-100 ) in people with type 1 diabetes mellitus . Methods In two double-blind , r and omized , crossover studies , 18 Japanese participants ( aged 20–65 years ) and 24 European participants ( aged 18–65 years ) with glycated haemoglobin levels ≤9.0 % ( ≤75 mmol/mol ) received single subcutaneous doses of Gla-300 , 0.4 , 0.6 and 0.9 U/kg ( 0.9 U/kg in the European study only ) , and Gla-100 , 0.4 U/kg . A 36-h euglycaemic clamp procedure was performed after each dosing . Results The serum insulin glargine concentration ( INS ) and glucose infusion rate ( GIR ) developed more gradually into more constant and prolonged profiles with Gla-300 than with Gla-100 . In support of this , the times to 50 % of glargine exposure and insulin activity were longer for all Gla-300 doses than for Gla-100 during the 36-h clamp period , indicating a more evenly distributed exposure and metabolic effect beyond 24 h. Exposure to insulin glargine and glucose utilization were lower with the 0.4 and 0.6 U/ml Gla-300 doses in both studies compared with the 0.4 U/ml Gla-100 dose . Glucose-lowering activity was detected for up to 36 h with all doses of Gla-300 . Conclusions Single-dose injections of Gla-300 present more constant and prolonged PK and PD profiles compared with Gla-100 , maintaining blood glucose control for up to 36 h in euglycaemic clamp setting s in Japanese and European participants with type 1 diabetes AIMS Data on the impact of hypoglycaemia on patients ' daily lives and diabetes self-management , particularly in developing countries , are lacking . The aim of this study was to assess fear of , and responses to , hypoglycaemia experienced by patients globally . MATERIAL S AND METHODS This non-interventional , multicentre , 4-week prospect i ve study using self- assessment question naires and patient diaries consisted of 27,585 patients , ≥18years , with type 1 diabetes ( n=8022 ) or type 2 diabetes ( n=19,563 ) treated with insulin for > 12months , at 2004 sites in 24 countries worldwide . RESULTS Increased blood glucose monitoring ( 69.7 % ) and seeking medical assistance ( 62.0 % ) were the most common responses in the 4weeks following hypoglycaemic events for patients with type 1 diabetes and type 2 diabetes , respectively . Approximately 44 % of patients with type 1 diabetes or type 2 diabetes increased calorie intake in response to a hypoglycaemic episode . Following hypoglycaemia , 3.9 % ( type 1 diabetes ) and 6.2 % ( type 2 diabetes ) of patients took leave from work or study . Regional differences in fear of , and responses to , hypoglycaemia were evident - in particular , a lower level of hypoglycaemic fear and utilisation of healthcare re sources in Northern Europe and Canada . CONCLUSIONS Hypoglycaemia has a major impact on patients and their behaviour . These global data for the first time reveal regional variations in response to hypoglycaemia and highlight the importance of patient education and management strategies Aims Insulin glargine 300 U/mL ( Gla‐300 ) offers a flatter pharmacodynamic profile than insulin glargine 100 U/mL ( Gla‐100 ) . We have compared these insulins over 1 year in people with type 1 diabetes ( T1DM ) . Methods EDITION 4 was a 6‐month , multicentre , r and omized , open‐label phase 3 study . People with T1DM who completed the 6 months continued r and omized Gla‐300 or Gla‐100 once daily , morning or evening , for a further 6 months . Results Among 549 participants r and omized , 444 completed the 12‐month study period ( Gla‐300 , 80 % ; Gla‐100 , 82 % ) . Mean HbA1c decreased similarly from baseline to month 12 in the 2 treatment groups ( difference , 0.02 [ 95 % CI , −0.13 to 0.17 ] ) % ‐units [ 0.2 ( − 
    Output:
    
Conclusions The best current evidence indicates that Gla-300  reduces the incidence of nocturnal hypoglycemia with slight improvements in glycemic control compared with Gla-100 in both type 1 and type 2 diabetes adult patients