diabetes therapies can negatively affect health status / health - related quality of life ( hrqol ) because of regimen complexity or rigidity , fear of injections , hypoglycaemia and fear of hypoglycaemia 1,2 .
thus , reducing hypoglycaemia and providing a more predictable treatment regimen might be expected to improve hrqol .
insulin degludec ( ideg ) is a new basal insulin that offers advantages over previous basal insulins .
action profile , an ultra - long duration of action lasting beyond 42  h , and low within - patient variability 3 .
seven randomised , open - label , controlled , phase 3 trials of 26- or 52-weeks  duration using a treat - to - target non - inferiority design , all confirmed similar glycaemic control for ideg compared to insulin glargine ( iglar ) as expected in treat - to - target trials .
however , individual trials , as well as a prospectively planned meta - analysis , showed advantages for ideg over iglar with respect to hypoglycaemia 4 .
hrqol , another important treatment outcome , was measured in all of these trials using the sf-36 v2 questionnaire 5 and additional meta - analyses have shown that hrqol 6 , health utility 7 and mental health 8 are improved with ideg compared to iglar .
the analysis presented here includes previously unreported data from insulin - nave patients with type 2 diabetes who were studied for a total of 2  years in a 52-week trial with a 52-week extension ; this was the largest of the phase 3 trials in the ideg clinical development programme 9 . as previously reported 10 , at 105  weeks
, hba1c was similar for ideg and iglar ( estimated treatment difference [ etd ] 0.12%-points [ 0.01 to 0.25]95% ci , p  =  0.078 ) .
observed mean reductions in laboratory - measured fasting plasma glucose ( fpg ) were greater with ideg ( etd 0.38
mmol / l [ 0.70 to 0.06]95% ci , p  =  0.019 ) .
importantly , these improvements in glycaemic control were accompanied by a lower risk of hypoglycaemia over the entire treatment period . nocturnal confirmed hypoglycaemia was 43% lower with ideg than with iglar ( estimated rate ratio [ err ] , ideg / iglar : 0.57 [ 0.40 ; 0.81]95%ci , p  =  0.002 ) and rate of severe hypoglycaemia was 69% lower with ideg ( err 0.31 [ 0.11 ; 0.85]95%ci , p  =  0.023 ) . overall confirmed hypoglycaemia ( plasma glucose  <  3.1 mmol / l or severe ) was similar between ideg and iglar ; estimated rate ratio ( ideg / iglar ) : err 0.84 [ 0.68 ; 1.04]95%ci , p  =  0.115 10 .
given that the clinical benefit of reduced hypoglycaemia occurred in conjunction with improved glucose control after 2  years of treatment , improvements in hrqol might also be expected . in the original 52-week trial , participants treated with ideg showed improvements in clinical measures and reported greater improvements in 
overall physical and  physical functioning short form 36 ( sf-36 ) scores compared with iglar 9 .
the aim of this subanalysis at 105  weeks was to compare ideg versus iglar with respect to change in health status from baseline ( initiation of basal insulin therapy ) in patients with type 2 diabetes , using the sf-36 v2 questionnaire .
subjects provided informed consent and re - started treatment with ideg or iglar at the same dose levels at end - of - treatment in the main trial 9 with optional adjustment at the discretion of the investigator . at the end of the core trial , patients were transferred to neutral protamine hagedorn insulin for 7  days to allow for insulin antibody evaluation .
the insulin dose at the end of the core trial was used as a starting point , and was titrated to a target fpg of 3.94.9  mmol / l based upon the mean pre - breakfast self - measured blood glucose for the preceding 23 consecutive days .
all assessments for efficacy and safety in this extension trial were as described for the core trial 9 .
health status was measured at baseline ( time of randomisation of the core trial ) , at 52  weeks , and at 105  weeks using the sf-36 v2 questionnaire .
the sf-36 scale is a validated multi - purpose questionnaire that has raw , norm - based scores with a mean ( standard deviation ) of 50 ( 10 ) .
the sf-36 questions are grouped into eight domains ( figure 1 ) , including a physical component summary ( pcs ) score and a mental component summary score .
patients were provided with instructions and given privacy to complete the questionnaires , which were sealed in envelopes and not reviewed by local investigators or study nurses .
scores from the intent - to - treat population were analysed using anova , with treatment , therapy at screening , sex and region as fixed factors , and age and relevant baseline values as covariates .
the long study duration was considered sufficient to ensure that any initial patient reporting bias was minimal .
as previously reported , 607 ( 79% ) of 773 patients randomised to ideg and 197 ( 77% ) of 257 randomised to iglar completed the core trial of 52  weeks 10 .
a total of 551 ( 71% ) of those initially randomised to ideg and 174 ( 68% ) of those initially randomised to iglar continued into the extension study on the core phase treatment allocation , with 505 ( 65% ) of those continuing on ideg and 154 ( 60% ) continuing on iglar completing the entire 104  weeks of treatment .
baseline characteristics have previously been reported , and were well - matched between treatment groups 10 .
health status results for the full analysis set are summarised in table1 . at 105  weeks ,
the changes from baseline in overall pcs score , physical functioning score and bodily pain score were statistically significantly ( p  <  0.05 ) in favour of ideg compared with iglar , with etds ( ideg / iglar ) of 1.1 [ 0.1 ; 2.1]95%ci , 1.1 [ 0.0 ; 2.3]95%ci and 1.5 [ 0.2 ; 2.9]95%ci , respectively .
when only completers were used , scores tended to further improve in favour of ideg compared to the full analysis set , but because of the lower number of respondents and loss of statistical power , only the bodily pain domain remained statistically significant .
short form 36 ( sf-36 ) scores at end - of - trial ci , confidence interval ; ideg , insulin degludec ; iglar , insulin glargine ; od , once daily . significantly better ( p  <  0.05 )
. data are estimated mean    standard error of the mean , full analysis set .
the score and change from baseline in the score at 105 weeks were analysed using an ancova model .
the statistically significant difference in pcs , physical functioning score in favour of ideg was maintained after 2  years treatment as also reported in the core 52  weeks of the trial 9 .
in addition to sustaining the significant difference in pcs and physical functioning , the bodily pain domain also was significantly in favour of ideg after 2  years .
these results are consistent with meta - analysis results of previous studies of ideg reporting improvements in sf-36 scores 6 and improvements in health utility versus iglar 7 .
similarly , earlier studies have reported improvements in various patient - reported outcomes when iglar was compared against oral therapy or other basal insulins 11 .
with respect to the clinical implications of these results , in diabetes , it has been estimated that a 1-point difference on pcs and physical functioning scores , for example , is associated with a 59% increase in mortality risk , a 24% increased risk of hospitalisation within 6  months and a 712% increased risk of being unable to work 12 .
although the sf-36 does not have an established minimal important difference in diabetes , the sf-36 v2 user manual suggests that even small differences in these compressed scores ( < 1 ) are relevant in other chronic diseases .
the precise reason for the improvement in sf-36 scores has not been determined . however , as mentioned earlier , ideg has been shown to have a beneficial effect on hypoglycaemia compared to iglar 4 .
hypoglycaemic events , both non - severe and severe , are known to be a key marker for reduced hrqol in diabetes 1 .
also , the sf-36 physical functioning score includes measures of vigorous activity , which may be enhanced if hypoglycaemia is less of a concern .
given that clinical trials exclude people at high risk of hypoglycaemia , the benefit may be even greater in real - world settings .
although an open - label design could have affected results of this study , the baseline values for sf-36 were collected prior to randomisation , and the long duration of the main trial plus extension study should have allowed any bias associated with initiation of a particular therapy to be minimised .
this study emphasises that patient - reported outcomes , which are an important measure of any diabetes treatment , can be improved with ideg .
h. w. r. has received grants / research support from amylin , eli lilly , merck and sanofi - aventis ; served as a consultant for biodel ; served on advisory panels of amylin pharmaceuticals , roche diagnostics , astrazeneca , biodel , novartis , novo nordisk , janssen , bristol - myers squibb and sanofi - aventis ; served on the speakers bureau for amylin pharmaceuticals , astrazeneca , bristol - myers squibb , boehringer ingelheim , eli lilly , merck and co. , and novo nordisk .
b. c. has served on the advisory panel for eli lilly and company , genfit , novo nordisk and sanofi - aventis and received grants / research support from novo nordisk and sanofi - aventis .
b. z. has served on the advisory panel for eli lilly and company , novo nordisk , and sanofi - aventis and received research support from novo nordisk .
y. h. has received grants / research support from boehringer ingelheim , conjuchem , daiichi sankyo , glaxosmithkline , lexicon , novo nordisk , takeda , sanofi - aventis , xoma , and tolerx ; served as consultant for amylin pharmaceuticals , daiichi - sankyo , gilead , genetech , glaxosmithkline , novo nordisk , merck , xoma , tolerx , janssen , halozyme , amarin , liposcience and santarus ; served on speakers bureau for amylin , astrazeneca , boehringer ingelheim , bristol - myers squibb , daiichi - sankyo , eli lilly ,
glaxosmithkline , novo nordisk , and santarus ; and is president of the american association of clinical endocrinologists . m. l. w. and a. r. are employees of novo nordisk and own stock in the company .
c. m. has served on the advisory panel for novo nordisk , sanofi - aventis , merck sharp and dohme ltd .
, eli lilly and company , novartis , bristol - myers squibb , astrazeneca lp , pfizer , johnson and johnson , and mannkind ; has received research support from novo nordisk , sanofi - aventis , merck sharp and dohme ltd . ,
eli lilly and company , and novartis ; and has served on the speakers bureau for novo nordisk , sanofi - aventis , merck sharp and dohme , eli lilly and company , and novartis .
all authors ( h. w. r. , b. c. , b. z. , y. h. , m. l. w. , a. r. and c. m. ) were involved in critical analysis and interpretation of the data , drafting / critically revising the article and shared in the final responsibility for the content of the manuscript and the decision to submit it for publication .
 insulin degludec ( ideg ) is a new basal insulin with an ultra - long and stable glucose - lowering effect . 
 we compared once - daily ideg and insulin glargine ( iglar ) , both in combination with metformin    dipeptidyl peptidase-4 inhibitors , in a 52-week , open - label , treat - to - target trial in patients with type 2 diabetes followed by a 52-week extension trial in which subjects [ n  =  725/1030 ( 70.4% ) ] maintained their initial randomised treatment . health status was assessed at baseline and 105  weeks using the short form-36 ( sf-36 v2 ) questionnaire . 
 sf-36 scores were analysed ( itt population ) using anova , with adjustments for covariates . at 105  weeks , the overall physical component score was significantly better with ideg versus iglar [ treatment contrast ( tc ) : 1.1 ( 0.1 ; 2.1)95%ci , p  <  0.05 ] . 
 this was largely because of significantly better physical functioning [ tc : 1.1 ( 0.0 ; 2.3)95%ci , p  <  0.05 ] and bodily pain sub - domain scores [ tc : 1.5 ( 0.2 ; 2.9)95%ci , p  <  0.05 ] . 
 improvements in health status with ideg compared to iglar were maintained after 2  years . 
Introduction
Methods
Results
Discussion
Conflict of Interest
Author declaration