despite the availability of a large number of therapeutic agents for the management of type 2 diabetes ( t2d ) , patients continue to present with high levels of glycated hemoglobin a1c ( hba1c ) in actual clinical practice .
insulin is the most potent therapy for t2d ; however , physicians often take a conservative approach to insulin dose optimization citing lack of familiarity and the risks of hypoglycemia and weight gain as some of the main concerns associated with its use .
it is acknowledged that insulin therapy tailored towards the requirements of individual patients would be more effective in helping patients manage hyperglycemia , while mitigating the risks of hypoglycemia and weight gain . a study by riddle et al .
suggests that basal ( fasting ) glucose , rather than postprandial plasma glucose ( pppg ) , tends to contribute more towards overall hyperglycemia at higher hba1c levels in t2d patients .
basal insulin therapy could therefore help decrease hyperglycemia in t2d patients by providing additional glycemic control .
insulin detemir ( idet ) is a basal insulin analogue with a protracted duration of action compared to neutral protamine hagedorn ( nph ) insulin .
idet remains soluble in the subcutaneous depot following injection , which may contribute to its lower within - subject variability with regard to nph insulin and another basal analogue , insulin glargine ( iglar ) .
studies have found that idet provides hba1c reductions in t2d patients comparable to those provided by iglar and nph insulin .
idet therapy is also associated with significantly less weight gain compared to iglar and nph insulin in t2d management .
it has also been noted that glycemic control improved following idet therapy in t2d patients previously treated with other basal insulins in combination with oral glucose - lowering drugs ( oglds ) . in india ,
the t2d epidemic is widespread with a reported diabetes prevalence of 9.0% in 2011 . by 2030 ,
the diabetes prevalence is set to increase to 10.6% , marking the urgent need to improve t2d management in the country . in developing nations such as india where diabetic complications are common and
a large segment of the population is of working age , the high t2d prevalence can have serious economic implications as well . evidence from randomized controlled trials
however , the patient populations of these trials are selected based on restrictive criteria and may not be truly representative of the patients seen in actual clinical practice .
large observational studies such as a1chieve , on the other hand , can provide relevant and timely data that would help in gauging patient responses to different therapies in a heterogeneous setting .
this sub - analysis of the a1chieve study aimed to determine the clinical safety and effectiveness of insulin detemir in indian patients switched from previous nph insulin or iglar therapy .
in the open - label , 24-week , non - interventional a1chievestudy , the clinical safety and effectiveness of the novo nordisk insulin analogs , idet ( levemir ) , biphasic insulin as part 30 ( novomix 30 ) and insulin as part ( novorapid ) in the treatment of t2d was evaluated in routine clinical care . here , the clinical safety and effectiveness of idet was explored in indian patients switched from either iglar or nph insulin .
have described the methods and procedures of the a1chieve study in detail . in brief , the prescription of idet was determined by the local physicians , who also supervised all aspects of the patients treatment .
the physicians performed all evaluations at routine visits to the local clinics , following which the data were transferred to standard case report forms .
indian patients switching therapy from either pre - study iglaror nph insulin to idet were included in this sub - analysis .
patients were excluded if they had received treatment with any of the study insulins for more than 4 weeks before the start of the study .
pregnant or breastfeeding women were excluded as were those who intended to become pregnant within 6 months from the start of the study .
study approval was obtained from the relevant local authorities and signed informed consent was obtained from all patients .
the primary outcome measure was the incidence of serious adverse drug reactions ( sadrs ) , including major hypoglycemic events , from baseline to week 24 .
secondary outcomes included the number of serious adverse events ( saes ) and the changes in the proportion of patients reporting hypoglycemic events in the 4 weeks before baseline and week 24 .
additional outcomes comprised the change from baseline to week 24 in hba1c , fasting plasma glucose ( fpg ) , pppg , systolic blood pressure ( sbp ) , body weight , lipids ( total cholesterol , triglycerides , high - density lipoprotein [ hdl ] cholesterol , and low - density lipoprotein [ ldl ] cholesterol ) and quality of life ( qol ) .
qol was determined using the euroqol visual analogue scale ( eq - vas ) that rates an individual 's current health state on a scale of 0 ( worst score ) to 100 ( best score ) .
local laboratories were used for laboratory measurements and followed local standardization and quality control procedures .
statistical analyses were performed for indian patients switching from pre - study iglar and nph insulin .
descriptive statistics ( mean , sd ) and frequency tables ( n , % ) were used to summarize continuous and discrete variables , respectively . the change from baseline to week 24 in the proportion of patients reporting at least one event of hypoglycemia
the change from baseline to week 24 for hba1c , fpg , pppg , sbp , body weight , lipids , and qol was analyzed using a paired t - test .
no p values are presented as the number of patients analyzed was less than 100 for all endpoints .
in the open - label , 24-week , non - interventional a1chievestudy , the clinical safety and effectiveness of the novo nordisk insulin analogs , idet ( levemir ) , biphasic insulin as part 30 ( novomix 30 ) and insulin as part ( novorapid ) in the treatment of t2d was evaluated in routine clinical care . here , the clinical safety and effectiveness of idet was explored in indian patients switched from either iglar or nph insulin .
have described the methods and procedures of the a1chieve study in detail . in brief , the prescription of idet was determined by the local physicians , who also supervised all aspects of the patients treatment .
the physicians performed all evaluations at routine visits to the local clinics , following which the data were transferred to standard case report forms .
indian patients switching therapy from either pre - study iglaror nph insulin to idet were included in this sub - analysis .
patients were excluded if they had received treatment with any of the study insulins for more than 4 weeks before the start of the study .
pregnant or breastfeeding women were excluded as were those who intended to become pregnant within 6 months from the start of the study .
study approval was obtained from the relevant local authorities and signed informed consent was obtained from all patients .
the primary outcome measure was the incidence of serious adverse drug reactions ( sadrs ) , including major hypoglycemic events , from baseline to week 24 .
secondary outcomes included the number of serious adverse events ( saes ) and the changes in the proportion of patients reporting hypoglycemic events in the 4 weeks before baseline and week 24 .
additional outcomes comprised the change from baseline to week 24 in hba1c , fasting plasma glucose ( fpg ) , pppg , systolic blood pressure ( sbp ) , body weight , lipids ( total cholesterol , triglycerides , high - density lipoprotein [ hdl ] cholesterol , and low - density lipoprotein [ ldl ] cholesterol ) and quality of life ( qol ) .
qol was determined using the euroqol visual analogue scale ( eq - vas ) that rates an individual 's current health state on a scale of 0 ( worst score ) to 100 ( best score ) .
local laboratories were used for laboratory measurements and followed local standardization and quality control procedures .
statistical analyses were performed for indian patients switching from pre - study iglar and nph insulin .
descriptive statistics ( mean , sd ) and frequency tables ( n , % ) were used to summarize continuous and discrete variables , respectively . the change from baseline to week 24 in the proportion of patients reporting at least one event of hypoglycemia
the change from baseline to week 24 for hba1c , fpg , pppg , sbp , body weight , lipids , and qol was analyzed using a paired t - test .
no p values are presented as the number of patients analyzed was less than 100 for all endpoints .
a total of 102 patients switched therapy from pre - study iglar to idet ( gla group ) , while 39 patients switched from pre - study nph insulin to idet ( neu group ) .
demographic and baseline characteristics of the gla and neu groups are presented in table 1 .
demographic and baseline characteristics by pre - study basal insulin regimen at baseline , the most commonly used oglds were metformin and sulfonylureas in both groups [ table 1 ] .
the three most common reasons reported by physicians for therapy change were to improve glycemic control ( for 96.1% of patients ) , reduce the risk of hypoglycemia ( 42.2% of patients ) and improve weight control ( 32.4% of patients ) in the gla group . in the neu group , the most common reasons for therapy change were to improve glycemic control ( 97.4% of patients ) , reduce the risk of hypoglycemia ( 51.3% of patients ) and try a new insulin ( 25.6% of patients ) .
insulin dose and frequency by pre - study basal insulin regimen the mean pre - study iglar dose was 0.26  0.13 u / kg , and 84.3% of patients followed qd dosing .
the mean idet dose was 0.23  0.09 u / kg at baseline and 0.25  0.12 u / kg at week 24 . at baseline , 87.3% of patients
dosed idet qd , while at week 24 , 62.7% and 37.3% of patients followed qd and bid dosing , respectively . the mean pre - study nph insulin dose was 0.27  0.16 iu / kg , and 64.1% and 35.9% of patients followed qd and bid dosing , respectively . at baseline and week 24 ,
the mean idet dose was 0.24  0.09 u / kg and 0.28  0.09 u / kg , respectively .
while 87.2% of patients followed qd dosing at baseline , 67.7% and 32.3% of patients followed qd and bid dosing , respectively , at week 24 .
there were no sadrs , saes , or major hypoglycemic events reported in either group throughout the study . in the gla group , 11.8% of patients reported overall hypoglycemia at baseline compared to 7.5% at week 24 [ table 3 ] .
the corresponding incidence rates of overall hypoglycemia were 2.80 events per patient - year and 1.36 events per patient - year , respectively .
no nocturnal hypoglycemic events were reported at week 24 in the gla group [ table 3 ] .
outcomes for hypoglycemia by pre - study basal insulin regimen at baseline in the neu group , 10.3% of patients reported overall hypoglycemia , corresponding to an incidence rate of 2.33 events per patient - year [ table 3 ] . at week 24 , no hypoglycemic event of any category was reported in the neu group . in the gla group , the mean 
sd hba1c was 9.9  1.8% at baseline compared to 7.6  0.9% at week 24 ( mean change : 2.3
the mean hba1c level was 9.1  1.2% at baseline and 7.3  0.7% at week 24 ( mean change : 1.7  0.9% ) .
fifteen patients had hba1c levels of < 7.0% at week 24 in the gla group compared to 3 patients at baseline . in the neu group , 6 patients had hba1c levels of < 7.0% at week 24 compared to 1 patient at baseline .
the mean fpg and pppg levels also appeared to improve from baseline to week 24 in the gla and neu groups [ table 4 ] .
glycemic parameters by pre - study basal insulin the mean levels of total cholesterol , triglycerides , and ldl cholesterol appeared to improve over 24 weeks in the gla and neu groups , while the mean hdl cholesterol levels appeared unchanged in both groups [ table 5 ] .
outcomes for lipid profile , body weight and sbp by pre - study basal insulin regimen in the gla group , the mean body weight was 72.1  11.7 kg at baseline and 72.3  11.3 kg at week 24 [ table 5 ] . over the same period in the neu group ,
the mean body weight was 69.5  13.0 kg and 69.8  12.4 kg , respectively . at baseline and week 24 , the mean sbp was 131.6  13.8 mmhg and 128.5  15.7 mmhg , respectively , in the gla group , and 140.5  16.0 mmhg and 132.8  12.2 mmhg , respectively , in the neu group [ table 5 ] . in the gla group ,
the mean qol score on the eq - vas was 56.2  10.9 points at baseline compared to 72.4  10.5 points at week 24 . in the neu group ,
the mean qol score was 56.6  6.7 points at baseline and 73.8  9.9 points at week 24 .
a total of 102 patients switched therapy from pre - study iglar to idet ( gla group ) , while 39 patients switched from pre - study nph insulin to idet ( neu group ) .
demographic and baseline characteristics of the gla and neu groups are presented in table 1 .
demographic and baseline characteristics by pre - study basal insulin regimen at baseline , the most commonly used oglds were metformin and sulfonylureas in both groups [ table 1 ] .
the three most common reasons reported by physicians for therapy change were to improve glycemic control ( for 96.1% of patients ) , reduce the risk of hypoglycemia ( 42.2% of patients ) and improve weight control ( 32.4% of patients ) in the gla group . in the neu group , the most common reasons for therapy change were to improve glycemic control ( 97.4% of patients ) , reduce the risk of hypoglycemia ( 51.3% of patients ) and try a new insulin ( 25.6% of patients ) .
insulin dose and dosing frequency details are presented in table 2 . insulin dose and frequency by pre - study basal insulin regimen
the mean pre - study iglar dose was 0.26  0.13 u / kg , and 84.3% of patients followed qd dosing .
the mean idet dose was 0.23  0.09 u / kg at baseline and 0.25  0.12 u / kg at week 24 . at baseline , 87.3% of patients
dosed idet qd , while at week 24 , 62.7% and 37.3% of patients followed qd and bid dosing , respectively .
the mean pre - study nph insulin dose was 0.27  0.16 iu / kg , and 64.1% and 35.9% of patients followed qd and bid dosing , respectively . at baseline and week 24 ,
the mean idet dose was 0.24  0.09 u / kg and 0.28  0.09 u / kg , respectively .
while 87.2% of patients followed qd dosing at baseline , 67.7% and 32.3% of patients followed qd and bid dosing , respectively , at week 24 .
there were no sadrs , saes , or major hypoglycemic events reported in either group throughout the study . in the gla group , 11.8% of patients reported overall hypoglycemia at baseline compared to 7.5% at week 24 [ table 3 ] .
the corresponding incidence rates of overall hypoglycemia were 2.80 events per patient - year and 1.36 events per patient - year , respectively .
no nocturnal hypoglycemic events were reported at week 24 in the gla group [ table 3 ] .
outcomes for hypoglycemia by pre - study basal insulin regimen at baseline in the neu group , 10.3% of patients reported overall hypoglycemia , corresponding to an incidence rate of 2.33 events per patient - year [ table 3 ] . at week 24 , no hypoglycemic event of any category was reported in the neu group .
in the gla group , the mean  sd hba1c was 9.9  1.8% at baseline compared to 7.6  0.9% at week 24 ( mean change : 2.3  1.7% ) . in the neu group , the mean hba1c level was 9.1  1.2% at baseline and 7.3  0.7% at week 24 ( mean change : 1.7  0.9% ) .
fifteen patients had hba1c levels of < 7.0% at week 24 in the gla group compared to 3 patients at baseline . in the neu group , 6 patients had hba1c levels of < 7.0% at week 24 compared to 1 patient at baseline .
the mean fpg and pppg levels also appeared to improve from baseline to week 24 in the gla and neu groups [ table 4 ] .
the mean levels of total cholesterol , triglycerides , and ldl cholesterol appeared to improve over 24 weeks in the gla and neu groups , while the mean hdl cholesterol levels appeared unchanged in both groups [ table 5 ] .
outcomes for lipid profile , body weight and sbp by pre - study basal insulin regimen in the gla group , the mean body weight was 72.1  11.7 kg at baseline and 72.3  11.3 kg at week 24 [ table 5 ] . over the same period in the neu group , the mean body weight was 69.5  13.0 kg and 69.8  12.4 kg , respectively . at baseline and week 24 , the mean sbp was 131.6  13.8 mmhg and 128.5  15.7 mmhg , respectively , in the gla group , and 140.5  16.0 mmhg and 132.8  12.2 mmhg , respectively , in the neu group [ table 5 ] .
in the gla group , the mean qol score on the eq - vas was 56.2  10.9 points at baseline compared to 72.4  10.5 points at week 24 . in the neu group , the mean qol score was 56.6  6.7 points at baseline and 73.8  9.9 points at week 24 .
this sub - analysis demonstrated the clinical safety and effectiveness of idet therapy in indian patients with t2d switched from iglar and nph insulin .
as observed in the overall a1chieve study , idet therapy appeared to be associated with beneficial effects on glycemic parameters and hypoglycemia .
glycemic control was sub - optimal at baseline in patients previously treated with iglar and nph insulin . in the gla group , patients had a mean baseline hba1c of 9.9  1.8% , diabetes duration of 9.0  5.7 years and had been taking insulin for an average of 2.6  2.0 years . in the neu group ,
the mean baseline hba1c level was 9.1  1.2% , diabetes duration was 8.9  6.3 years and patients had been on insulin therapy for an average of 2.5  2.9 years .
switching to idet therapy was seen to be well - tolerated in the gla and neu groups with no sadrs , saes , or major hypoglycemic events reported during the study .
clinical trials have not identified any difference between idet and iglar with regard to the risk of hypoglycemia . in this sub - analysis ,
the incidence rate of overall hypoglycemia was 2.80 events per patient - year at baseline and 1.36 events per patient - year at week 24 in the gla group .
no nocturnal hypoglycemic events were reported at week 24 in the gla group against an incidence rate of 1.91 events per patient - year at baseline .
idet has been noted to have a significantly lower risk association for hypoglycemia than nph insulin in 2 randomized controlled trials in patients with t2d . in the neu group in this study ,
no events of hypoglycemia were reported at week 24 against a baseline incidence rate of 2.33 events per patient - year .
glycemic parameters appeared to improve after 24 weeks in both the gla and neu groups . at week 24 , the mean hba1c was 7.6  0.9% in the gla group and 7.3  0.7% in the neu group .
however , these levels still fall short of the internationally recommended hba1c target of < 7.0% . also , the number of patients meeting the hba1c target of < 7.0% at week 24 was low in both groups .
most patients ( > 60% ) in both the gla and neu groups followed qd dosing of idet at week 24 , with the remaining patients following bid dosing . in the gla group ,
the mean daily insulin dose by weight was 0.23  0.09 u / kg at baseline and 0.25  0.12 u / kg at week 24 .
in the neu group also , the difference in mean dose between baseline and week 24 was small ( 0.24  0.09 and 0.28  0.09 , respectively ) , suggesting that perhaps the physicians were overly cautious in applying dose titration .
it is possible that a more aggressive approach to dose titration may have led to more effective reductions in glycemic levels and more patients achieving the recommended hba1c target at week 24 .
a general lack of insulin dose optimization in clinical practice in india has also been identified in the prospective 26-week impact study , which evaluated the effectiveness of the indian insulin guideline on premixed insulin .
mean body weights remained very similar from baseline to week 24 in both the gla and neu groups , in line with the known weight - sparing effect of idet therapy .
the mean qol also appeared to improve with idet therapy in both groups , in line with the overall a1chieve study results that showed a significant improvement in qol in patients treated with idet .
this study may have been limited by the lack of a control group and the possible introduction of recall bias in the reporting of safety data , particularly hypoglycemic events .
the small number of patients in this sub - analysis was also a limiting factor .
concomitant medication and diet were not restricted ; hence , it was not possible to determine the effect , if any , of non - pharmacological treatment on the study outcomes .
the heterogeneity of the local healthcare systems meant that there was no standardization across sites .
however , this study provided the opportunity to study the effect of switching therapy from nph insulin and iglar to idet in the routine clinical setting in india .
all measurements made by the laboratories followed local standardization procedures and the 24-week duration of the study was considered adequate to determine the preliminary clinical trend following therapy change .
data from non - interventional studies such as a1chieve can help bridge the gap between recommended healthcare policies for t2d and actual clinical practice . also , patient education can play a key role in improving compliance to blood glucose monitoring , weight control , diet and exercise . a holistic approach to the treatment of t2d , involving increased patient education
, recommendations for diet and exercise and therapeutic strategies that target glycemic levels without increasing the risk of hypoglycemia and weight gain , may be indicated to improve patient compliance and facilitate disease management . in this sub - analysis ,
idet therapy was noted to be well - tolerated with minimal change in weight and a low risk of hypoglycemia in patients switched from nph insulin and iglar .
it would be interesting to note the effect of additional dose titration with idet over a further period of evaluation in a larger patient group .
 aim : to explore the clinical safety and effectiveness of insulin detemir ( idet ) in a subgroup of indian patients with type 2 diabetes ( t2d ) switched from either insulin glargine ( iglar ) or neutral protamine hagedorn ( nph ) insulin in the 24-week , non - interventional a1chieve study.materials and methods : indian patients with t2d switching from pre - study iglaror nph insulin to idet were included . 
 safety and effectiveness outcomes were evaluated by the physicians in local clinical settings.results:a total of 102 patients switched from iglar to idet ( gla group ) and 39 patients switched from nph insulin to idet ( neu group ) . at baseline , 
 the mean glycated hemoglobin a1c ( hba1c ) levels were 9.9  1.8% in the gla group and 9.1  1.2% in the neu group . 
 no serious adverse drug reactions , serious adverse events , or major hypoglycemic events were reported in either group throughout the study . at baseline and week 24 , 11.8% and 7.5% of patients , respectively , reported overall hypoglycemic events in the gla group . 
 no hypoglycemic events were reported at week 24 in the neu group . at week 24 , the mean hba1c levels were 7.6  0.9% in the gla group and 7.3  0.7% in the neu group . 
 the mean fasting plasma glucose , postprandial plasma glucose and quality of life also appeared to improve over 24 weeks.conclusion:switching to idet therapy from iglar and nph insulin was well - tolerated and appeared to be associated with improved glycogenic control in indian patients . 