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Insulin detemir in the management of type 2 diabetes in non-Western countries: Safety and effectiveness data from the A1chieve observational study

Alexey Zilov, Nabil El Naggar, Siddharth Shah, Chunduo Shen and Jihad Haddad

Diabetes Research and Clinical Practice, 3, 101, pages 317 - 325

Received 24 December 2012, Revised 16 May 2013, Accepted 6 June 2013, Published online Oct-2013


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3. Results

3.1. Study participants

Among the 66,726 people who were enrolled in the A1chieve study, 15,545 started insulin therapy with or switched to detemir ± OGLDs. A total of 86.9% completed the study treatment period, 13.1% withdrew, 7.5% lost contact with their physician, 5.4% citied other reasons, and 0.2% reported adverse drug reactions. Prior to enrolment, 4.8% were receiving no medication for diabetes and 72.9% were being treated with OGLDs alone. Of the remaining 22.3% who were changing their insulin therapy, 64.4% transferred from human insulin (sub-divided as 50.6% from NPH, 35.6% from human premix, 8.1% from human soluble insulin, 4.2% from basal–bolus NPH/human insulin, and the remaining 1.5% from other insulins), 26.9% transferred from the basal insulin analogue glargine, and 8.7% transferred from other insulin therapies. Globally, mean (±SD) duration of diabetes was higher in the prior insulin user cohort (11.0 ± 7.0 vs. 7.6 ± 5.5 years). For insulin-naïve participants, the percentage of people using more than two OGLDs decreased by 58% (27.7% pre-study, 11.7% at 24 weeks). Metformin use was maintained (84%), but there were reductions in the percentages of people using sulphonylureas (84.3% pre-study, 64.0% at 24 weeks) and thiazolidinediones (23.6% pre-study, 11.3% at 24 weeks). For the participants changing insulin therapy, metformin use also remained consistent (∼80%), while sulphonylurea and thiazolidinedione use decreased (61.5% to 53.4%, and 14.0% to 9.2%, respectively. At the end of the study, the percentage of previously insulin-experienced participants using more than two OGLDs decreased from 11.5% (pre-study) to 9.9% after 24 weeks using insulin detemir.

Baseline demographics and regional distribution are shown in Table 1. The majority of patients starting basal insulin or switching to insulin detemir came from the Middle East/Gulf and East Asian regions (28.8 and 27.2%, respectively) (Table 1). Patient characteristics followed similar trends to the global cohort; regional differences of note were that the majority of patients from Russia were female (70.0%), while 65.5% from the Middle East/Gulf were male. Overall duration of diabetes was highest in Latin American countries and lowest in South Asia (11.6 ± 8.3 vs. 5.8 ± 4.3 years). Mean (±SD) body weight was highest at baseline in the Middle East and Gulf region and Russia (87.3 ± 15.0 and 85.0 ± 15.4 kg) and lowest in East Asia (64.6 ± 12.1 kg). In the prior insulin users groups, the mean duration of insulin treatment was 3.2 ± 3.9 years for the global cohort and was similar for most of the regions. Exceptions of note were Russia, where the mean duration of insulin treatment prior to the start of the trial was 2.5 ± 2.7 years and Latin America, where participants had been using insulin for 5.0 ± 5.5 years.

Table 1 Patient numbers and characteristics by pre-study therapy and regional distribution in the insulin detemir subgroup and entire A1chieve study population.

Demographic Insulin detemir subgroup population A1chieve study population
Global cohort Insulin-naïve Insulin- experienced Global cohort Insulin-naïve Insulin- experienced
n (%) 15,545 (100) 12,078 (77.7) 3467 (22.3) 66,726 (100) 44,872 (67.2) 21,854 (32.8)
Gender, M/F (%) 54.1/45.9 55.0/45.0 51.3/48.7 55.6/44.4 57.3/42.7 51.9/48.1
Age (years) 54.6 (11.5) 54.0 (11.3) 56.8 (11.9) 54.0 (12.0) 53.2 (11.6) 55.6 (12.5)
Body weight (kg) 76.6 (16.3) 76.5 (16.3) 76.7 (16.3) 72.9 (15.0) 71.7 (14.4) 75.3 (15.9)
BMI (kg/m2) 28.2 (5.3) 28.2 (5.3) 28.4 (5.5) 27.1 (5.0) 26.7 (4.7) 27.9 (5.50
Duration of diabetes (years) 8.4 (6.0) 7.6 (5.5) 11.0 (7.0) 8.0 (19) 80 (19) 79 (20)
>2 OGLDs, n (%) 1608 (11.7) 1320 (12.1) 288 (10.2) 10,981 (20.1) 8971 (23.1) 2010 (12.7)
HbA1c (% [mmol/mol]) 9.5 (1.6) [80] 9.5 (1.6) [80] 9.3 (1.7) [78] 9.5 (1.7) [80] 9.5 (1.7) [80] 9.4 (1.8) [79]
Geographic region (% of cohort)
China 137 (100) 88 (64.2) 49 (35.8) 11,020 (100) 8206 (74.4) 2814 (25.6)
South Asia 3079 (100) 2608 (84.7) 471 (15.3) 22,447 (100) 18,067 (80.5) 4380 (19.5)
East Asia 4230 (100) 3195 (75.5) 1035 (24.5) 10,032 (100) 6594 (65.7) 3438 (34.3)
North Africa 1746 (100) 1250 (71.6) 496 (28.4) 4039 (100) 1969 (48.7) 2070 (51.3)
Middle East and Gulf 4474 (100) 3560 (79.6) 914 (20.4) 14,976 (100) 7501 (50.1) 7475 (49.9)
Latin America 643 (100) 405 (63.0) 238 (37.0) 1138 (100) 636 (55.9) 502 (44.1)
Russia 1236 (100) 972 (78.6) 264 (21.4) 3074 (100) 1899 (61.8) 1175 (38.2)

References in context

  • The majority of patients starting basal insulin or switching to insulin detemir came from the Middle East/Gulf and East Asian regions (28.8 and 27.2%, respectively) (Table 1).
    Go to context

  • The majority of patients starting basal insulin or switching to insulin detemir came from the Middle East/Gulf and East Asian regions (28.8 and 27.2%, respectively) (Table 1).
    Go to context

Data are mean (SD), unless otherwise stated.

BMI, body mass index; OGLD, oral glucose-lowering drug.

The majority of people were insulin-naïve in all regions at baseline (range: 63.0% in Latin America to 84.7% in South Asia). Of the prior insulin users, the majority transferred from a human or analogue basal insulin regimen (64.7%). For the overall cohort, this was approximately a 50:50 split between basal analogue and human basal insulin but, regionally, basal analogue was more frequently prescribed in all regions except Russia and Latin America, where basal human insulin accounted for >85% of pre-study basal insulin choice. Overall, 23.8% of prior insulin users switched from a premix regimen (96.4% human insulin premix), which was most popular in South Asia (49.3%).

Baseline glucose control was poor regardless of pre-study treatment or geographical region. Baseline HbA1c was lowest in people switching from treatment with basal insulin glargine (9.0 ± 1.7% [75 mmol/mol]) and highest in the insulin-naïve cohort (9.5 ± 1.6% [80 mmol/mol]). Regionally, baseline HbA1c was lowest in North Africa 9.3 ± 1.7% [78 mmol/mol]) and highest in Latin America (9.6 ± 2.2% [81 mmol/mol]).

The most frequent reason given by physicians for introducing insulin detemir was to improve glycaemic control (95.5%). Other reasons included: to reduce plasma glucose variability (27.7%), reduce the risk of hypoglycaemia (23.9%), address patient dissatisfaction with current therapy (22.3%), control unstable diabetes (21.2%), and improve weight control (21.0%).

The prevalence of diabetic complications at baseline for the overall cohort were as follows: cardiovascular (26.8%), renal (28.4%), eye (26.5%), foot ulcer (4.4%), and neuropathic (40.1%). Figures were similar for most regions with the exception of Russia, where the prevalence of diabetes-related cardiovascular, eye, and neuropathy complications was notably higher (70.3, 64.7, and 81.1% respectively). Russia was also the only region to report similar prevalence of complications in both the insulin-naïve and prior insulin users. Diabetic renal complications were most prevalent in the Middle East/Gulf region (39.2%).

3.2. Primary safety outcomes

Out of a total of 15,545 patients, seven SADRs were reported by seven people; instances of hypoglycaemia were noted in four people and hyperglycaemia in three; of these adverse events, five instances were assessed as probably being related to treatment and two as possibly related.

3.3. Effectiveness outcomes

3.3.1. By pre-study therapy

Significant improvements in glycaemic control were associated with insulin detemir from baseline to final visit in insulin-naïve patients and prior insulin users. Mean reductions in HbA1c, FPG, and PPG were greater in the insulin-naïve subgroup than for prior insulin users (Table 2). Overall, the proportion of patients reaching HbA1c < 7.0% [53 mmol/mol] increased from 3.0% at baseline to 31.5% after 24 weeks; similar results were reported for the pre-study therapy subgroups (Table 2).

Table 2 Outcome measures by pre-study therapy in the insulin detemir subgroup and entire A1chieve study population.

Outcome measure Insulin detemir subgroup population A1chieve study population
Global cohort Insulin- naïve Insulin- experienced Global cohort Insulin- naïve Insulin- experienced
Insulin dose (U/kg/day) n 15,545 12,078 3467 66726 44872 21854
Pre-study 0.42 (0.24) 0.42 (0.24) 0.55 (0.29) 0.55 (0.29)
Baseline 0.27 (0.15) 0.24 (0.13) 0.35 (0.19) 0.44 (0.24) 0.38 (0.20) 0.55 (0.27)
Week 24 0.37 (0.20) 0.35 (0.18) 0.45 (0.24) 0.50 (0.26) 0.44 (0.22) 0.62 (0.30)
HbA1c (% [mmol/mol]) n 10,581 8459 2122 44,661 30, 369 14,292
Baseline 9.5 (1.6) [80] 9.5 (1.6) [80] 9.3 (1.7) [78] 9.5 (1.7) [80] 9.5 (1.7) [80] 9.4 (1.8) [79]
Week 24 7.5 (1.2) [58] 7.4 (1.1) [57] 7.6 (1.3) [60] 7.4 (1.1) [57] 7.4 (1.0) [57] 7.6 (1.2) [60]
Change −2.0 (1.6) [22] x EuroQol Group. EuroQol – a new facility for the measurement of health-related quality of life. Health Policy. 1990;16:199-208 −2.1 (1.6) [23] x L. Meneghini, C. Koenen, W. Weng, J.L. Selam. The usage of a simplified self-titration dosing guideline (303 Algorithm) for insulin detemir in patients with type 2 diabetes – results of the randomized, controlled PREDICTIVE 303 study. Diabetes Obes Metab. 2007;9:902-913 Crossref. −1.6 (1.7) [17] x C. Fajardo Montañana, C. Hernández Herrero, M. Rivas Fernández. Less weight gain and hypoglycaemia with once-daily insulin detemir than NPH insulin in intensification of insulin therapy in overweight Type 2 diabetes patients: the PREDICTIVE BMI clinical trial. Diabet Med. 2008;25:916-923 −2.1 (1.7) [23] x L. Meneghini, C. Koenen, W. Weng, J.L. Selam. The usage of a simplified self-titration dosing guideline (303 Algorithm) for insulin detemir in patients with type 2 diabetes – results of the randomized, controlled PREDICTIVE 303 study. Diabetes Obes Metab. 2007;9:902-913 Crossref. −2.2 (1.7) [23] x L. Meneghini, C. Koenen, W. Weng, J.L. Selam. The usage of a simplified self-titration dosing guideline (303 Algorithm) for insulin detemir in patients with type 2 diabetes – results of the randomized, controlled PREDICTIVE 303 study. Diabetes Obes Metab. 2007;9:902-913 Crossref. −1.8 (1.7) [19] x L.F. Meneghini, K.H. Rosenberg, C. Koenen, M.J. Merilainen, H.J. Lüddeke. Insulin detemir improves glycaemic control with less hypoglycaemia and no weight gain in patients with type 2 diabetes who were insulin naive or treated with NPH or insulin glargine: clinical practice experience from a German subgroup of the PREDICTIVE study. Diabetes Obes Metab. 2007;9:418-427 Crossref.
p-value <0.001 <0.001 <0.001 <0.001 <0.001 <0.001
People reaching HbA1c <7.0% n 13,190 (100.0) 10,376 (100.0) 2814 (100.0) 57,250 (100.0) 38,639 (100.0) 18,611 (100.0)
[53 mmol/mol] (%) Baseline 3.0 2.1 6.2 3.9 3.0 5.6
Week 24 31.5 31.7 30.3 31.8 32.0 31.3
FPG, pre-breakfast (mmol/L) n 10742 8560 2182 48,191 33,087 15,104
Baseline 10.9 (3.3) 11.2 (3.2) 9.9 (3.3) 10.9 (3.5) 11.2 (3.4) 10.5 (3.7)
Week 24 7.1 (2.0) 7.0 (1.9) 7.3 (2.3) 7.1 (1.9) 7.1 (1.8) 7.2 (2.2)
Change −3.9 (3.3) −4.2 (3.2) −2.6 (3.5) −3.8 (3.5) −4.1 (3.3) −3.2 (3.8)
p-value <0.001 <0.001 <0.001 <0.001 <0.001 <0.001
PPG (mmol/L), post-breakfast n 7148 5757 1391 33,742 23,334 10,408
Baseline 14.8 (4.2) 15.0 (4.2) 13.8 (4.3) 15.1 (4.4) 15.5 (4.3) 14.2 (4.5)
Week 24 9.6 (2.9) 9.5 (2.8) 9.9 (3.2) 9.7 (2.9) 9.8 (2.9) 9.7 (3.0)
Change −5.1 (4.3) −5.5 (4.2) −3.8 (4.3) −5.4 (4.5) −5.8 (4.4) −4.5 (4.6)
p-value <0.001 <0.001 <0.001 <0.001 <0.001 <0.001
Body weight (kg) n 11,934 9336 2598 50,059 33,716 16,343
Baseline 76.6 (16.3) 76.5 (16.3) 76.7 (16.3) 73.3 (14.8) 72.1 (14.3) 75.7 (15.7)
Week 24 76.2 (15.5) 76.2 (15.4) 76.0 (15.7) 73.3 (14.1) 72.2 (13.5) 75.7 (15.1)
Change −0.4 (4.0) −0.3 (4.0) −0.7 (3.6) 0.1 (3.7) 0.1 (3.7) −0.0 (3.6)
p-value <0.001 <0.001 <0.001 <0.001 <0.001 0.081
SBP (mmHg) n 11,620 9077 2543 45,285 29,595 15,690
Baseline 133.2 (16.7) 133.3 (16.7) 133.0 (16.9) 134.2 (17.8) 134.0 (17.7) 134.7 (18.0)
Week 24 128.0 (14.9) 127.9 (15.2) 128.4 (13.7) 127.9 (13.5) 127.3 (13.3) 129.0 (13.7)
Change −5.2 (17.3) −5.4 (17.7) −4.5 (15.6) −6.3 (17.1) −6.6 (17.4) −5.7 (16.6)
p-value <0.001 <0.001 <0.001 <0.001 <0.001 <0.001
Total cholesterol (mmol/L) n 5791 4529 1262 20, 293 11,994 8299
Baseline 5.3 (1.3) 5.3 (1.2) 5.2 (1.4) 5.3 (1.3) 5.4 (1.3) 5.2 (1.3)
Week 24 4.8 (1.0) 4.8 (0.9) 4.8 (1.0) 4.8 (1.0) 4.8 (1.0) 4.8 (1.0)
Change −0.5 (1.1) −0.6 (1.1) −0.4 (1.1) −0.5 (1.2) −0.6 (1.2) −0.4 (1.2)
p-value <0.001 <0.001 <0.001 <0.001 <0.001 <0.001
HDL cholesterol (mmol/L) n 4388 3418 970 17,306 10,189 7117
Baseline 1.1 (0.4) 1.1 (0.4) 1.1 (0.4) 1.1 (0.4) 1.2 (0.4) 1.1 (0.4)
Week 24 1.2 (0.4) 1.2 (0.3) 1.2 (0.4) 1.2 (0.4) 2.7 (0.4) 1.2 (0.4)
Change 0.0 (0.4) 0.0 (0.3) 0.0 (0.4) 0.1 (0.4) 0.1 (0.4) 0.0 (0.4)
p-value <0.001 <0.001 0.012 <0.001 <0.001 <0.001
LDL cholesterol (mmol/L) n 4428 3459 969 17,494 10,304 7190
Baseline 3.1 (1.0) 3.1 (1.0) 3.0 (1.0) 3.1 (1.0) 3.2 (1.0) 3.1 (1.1)
Week 24 2.7 (0.8) 2.7 (0.8) 2.7 (0.9) 2.8 (0.9) 2.7 (0.9) 2.8 (0.9)
Change −0.4 (1.0) −0.4 (1.0) −0.3 (0.9) −0.4 (1.0) −0.4 (1.0) −0.3 (0.9)
p-value <0.001 <0.001 <0.001 <0.001 <0.001 <0.001
Triglycerides (mmol/L) n 5413 4251 1162 19,856 11,672 8184
Baseline 2.1 (1.0) 2.1 (1.0) 1.9 (1.0) 2.1 (1.1) 2.1 (1.1) 2.0 (1.1)
Week 24 1.7 (0.7) 1.7 (0.7) 1.7 (0.8) 1.8 (0.7) 1.7 (0.7) 1.8 (0.7)
Change −0.3 (0.9) −0.4 (0.9) −0.2 (0.9) −0.3 (0.9) −0.4 (1.0) −0.3 (0.9)
p-value <0.001 <0.001 <0.001 <0.001 <0.001 <0.001

References in context

  • Overall, the proportion of patients reaching HbA1c<7.0% [53 mmol/mol] increased from 3.0% at baseline to 31.5% after 24 weeks; similar results were reported for the pre-study therapy subgroups (Table 2).
    Go to context

  • Overall, the proportion of patients reaching HbA1c<7.0% [53 mmol/mol] increased from 3.0% at baseline to 31.5% after 24 weeks; similar results were reported for the pre-study therapy subgroups (Table 2).
    Go to context

  • In prior insulin users, the pre-study mean insulin dose was 0.42±0.24 IU/kg/day, and 0.45±0.24 U/kg/day of insulin detemir at 24 weeks (Table 2).
    Go to context

  • Mean blood lipid profiles improved overall by −0.5±1.1 mmol/L; there was no clinically meaningful change in high-density lipoprotein (HDL) cholesterol, but low-density lipoprotein cholesterol (LDL) values fell by −0.4±1.0 mmol/L and triglycerides by −0.3±0.9 mmol/L (p<0.001) (Table 2).
    Go to context

  • Mean blood lipid profiles improved overall by −0.5±1.1 mmol/L; there was no clinically meaningful change in high-density lipoprotein (HDL) cholesterol, but low-density lipoprotein cholesterol (LDL) values fell by −0.4±1.0 mmol/L and triglycerides by −0.3±0.9 mmol/L (p<0.001) (Table 2).
    Go to context

  • Mean blood lipid profiles improved overall by −0.5±1.1 mmol/L; there was no clinically meaningful change in high-density lipoprotein (HDL) cholesterol, but low-density lipoprotein cholesterol (LDL) values fell by −0.4±1.0 mmol/L and triglycerides by −0.3±0.9 mmol/L (p<0.001) (Table 2).
    Go to context

Data are mean (SD) unless otherwise stated.

FPG, fasting plasma glucose; HDL, high-density lipoprotein; LDL, low-density lipoprotein; PPG, postprandial plasma glucose; SBP, systolic blood pressure.

In the insulin-naïve cohort, mean daily insulin dose was 0.24 ± 0.13 U/kg/day at baseline and 0.35 ± 0.18 U/kg/day at the end of the study. In prior insulin users, the pre-study mean insulin dose was 0.42 ± 0.24 IU/kg/day, and 0.45 ± 0.24 U/kg/day of insulin detemir at 24 weeks (Table 2). For the 3467 prior insulin users starting insulin therapy with detemir at baseline, the majority switched from NPH (32.6%, n = 1131), insulin glargine (26.9%, n = 934), or premix insulin (23.8%, n = 825).

Pre-study mean basal insulin doses were 0.38 ± 0.21 IU/kg/day (NPH) and 0.33 ± 0.17 U/kg/day (glargine); at 24 weeks insulin doses for these subgroups were 0.47 ± 0.23 U/kg/day and 0.42 ± 0.22 U/kg/day, respectively. Prior users of premix insulin reported a mean dose change from 0.51 + 0.24 IU/kg/day to 0.46 ± 0.24 U/kg/day of insulin detemir at 24 weeks. Prior to switching to insulin detemir, 53.6% of patients were on a once-daily insulin regimen. At the end of the study, 79.1% of people initiating insulin with detemir, and 70.0% of those transferring insulin therapy to detemir were using a once-daily regimen.

HbA1c decreased significantly from 9.1 ± 1.8% [76 mmol/mol] at baseline by −1.4 ± 1.7% [15 mmol/mol] (p < 0.001) by the end of the study for NPH users, from 9.0 ± 1.7% [75 mmol/mol] by −1.3 ± 1.7 [14 mmol/mol] for patients switched from insulin glargine, and from 9.5% ± 1.7% [80 mmol/mol] by −2.1 ± 1.7 [23 mmol/mol] in people changing from premix therapy (p < 0.001 for all). Significant improvements (p < 0.001) were also observed for FPG and PPG: −2.4 ± 3.6 mmol/L and −3.2 ± 4.0 mmol/L for NPH, −2.0 ± 3.3 mmol/L and −3.1 ± 4.3 mmol/L for prior insulin glargine users, and −3.4 ± 3.2 mmol/L and −4.9 ± 4.4 mmol/L for prior premix users, respectively.

3.3.2. Regional differences

At the end of the study, the percentage of people using a once-daily regimen with insulin detemir ranged from 38.4% in Russia to 88.1% in East Asia; figures were similar irrespective of prior study therapy. Mean insulin dose by region are reported in Supplementary Table 1.1.

HbA1c decreased significantly from baseline (p < 0.001) for all regions, ranging from −2.2% [24 mmol/mol] in the Middle East/Gulf region (n = 4474) to −1.4% [15 mmol/mol] in North Africa (n = 1746). The proportion of patients reaching HbA1c < 7.0% [53 mmol/mol] ranged from 36.8% in the Middle East and Gulf to 23.8% in North Africa. FPG and PPG values decreased significantly from baseline (p < 0.0001) for all regions (Supplementary Table 1.1), with the greatest reductions being observed in the Middle East and Gulf region (−4.2 mmol/L FPG; −6.0 mmol/L PPG) and Latin America (−4.1 mmol/L FPG; −6.5 mmol/L PPG).

3.4. Safety outcomes

3.4.1. Hypoglycaemia by pre-study therapy

The reported incidence of major hypoglycaemia decreased significantly over 24 weeks in both the insulin-naïve and prior insulin user subgroups (p < 0.0001). For people changing insulin to treatment with insulin detemir, significant reductions were also reported in the incidence of overall, minor, and nocturnal events (p < 0.0001 for all) (Fig. 1). The change in the incidence of overall hypoglycaemia from baseline to 24 weeks was from 12.44 to 2.26 events per patient-year for people previously treated with NPH, from 5.08 to 2.38 events per patient-year for prior insulin glargine users, and from 8.08 to 1.14 events per patient year for people switching from premix insulin.

Fig. 1 Changes in the incidence of hypoglycaemia in insulin-naïve and prior insulin users after 24 weeks of treatment with insulin detemir ± oral glucose-lowering drugs.

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References in context

  • For people changing insulin to treatment with insulin detemir, significant reductions were also reported in the incidence of overall, minor, and nocturnal events (p<0.0001 for all) (Fig. 1).
    Go to context

3.4.2. Hypoglycaemia by region

A reduction in the incidence of hypoglycaemic events was reported for all regions, but baseline values and the degree of the reduction varied greatly (Supplementary Table 1.2). Baseline rates for major hypoglycaemic events were highest in North Africa and Latin America (0.59 and 0.53 events per patient-year in 2.7 and 1.9% of the regional populations, respectively). South Asia reported the lowest baseline values, with 0.08 events per patient-year in 0.5% of the regional population (Supplementary Table 1.2). Overall, minor, and nocturnal hypoglycaemic events were observed to be highest at baseline in North Africa, Latin America, and Russia, while all three regions observed a decrease in the events per patient-year. Russia, unlike the other two regions, did not observe a significant decrease in the percentage of patients experiencing these events. South Asia reported the lowest incidence of overall and minor events at baseline, which were significantly reduced in the region at the end of the study (Supplementary Table 1.2).

3.5. Secondary clinical outcome measures

3.5.1. By pre-study therapy

The mean change in body weight over 24 weeks for all patients treated with insulin detemir was −0.4 ± 4.0 kg (p < 0.001). Both insulin-naïve and prior insulin user subgroups reported a reduction in body weight (Table 2). Mean change in body weight at 24 weeks was −0.6 ± 3.2 kg for the prior NPH users, −0.4 ± 3.9 kg for prior glargine users, and −1.0 ± 3.6 kg for people previously treated with premix insulin (p < 0.001 for all). Mean SBP decreased significantly for the entire cohort (−5.2 ± 17.3 mmHg; p < 0.001) to 128.0 ± 14.9 mmHg by the end of the study and in both pre-study therapy subgroups (Table 2). Mean blood lipid profiles improved overall by −0.5 ± 1.1 mmol/L; there was no clinically meaningful change in high-density lipoprotein (HDL) cholesterol, but low-density lipoprotein cholesterol (LDL) values fell by −0.4 ± 1.0 mmol/L and triglycerides by −0.3 ± 0.9 mmol/L (p < 0.001) (Table 2). There were no notable differences between the insulin-naïve and insulin experienced subgroups.

3.5.2. Regional differences

Five of the seven regions observed a reduction in mean body weight (China, South Asia, Middle East and Gulf, Russia and Latin America; see Supplementary Table 1.1). Mean SBP decreased in all regions. The largest decrease was observed in Russia (−8.5 ± 13.7 mmHg; p < 0.001), where mean baseline values were the highest of any participating region (141.2 ± 16.3 mmHg), with the smallest reduction being reported in North Africa (−1.6 ± 24.2 mmHg; p = 0.012). Total cholesterol values at baseline ranged between 4.6 ± 1.1 mmol/L (North Africa) and 6.0 ± 1.2 mmol/L (Russia). Reductions were reported for all regions between −0.2 ± 1.2 mmol/L (North Africa) and −0.6 ± 1.3 mmol/L (East Asia) and −0.6 ± 1.0 mmol/L (Middle East and Gulf). HDL cholesterol values remained generally unchanged as reported for the overall cohort, and all regions reported a decrease in LDL cholesterol and triglyceride levels (Supplementary Table 1.1). The degree of reduction in blood lipid profile values observed regionally did not appear to be related to the baseline value.

 
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Fig. 1 Changes in the incidence of hypoglycaemia in insulin-naïve and prior insulin users after 24 weeks of treatment with insulin detemir ± oral glucose-lowering drugs.

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References in context

  • For people changing insulin to treatment with insulin detemir, significant reductions were also reported in the incidence of overall, minor, and nocturnal events (p<0.0001 for all) (Fig. 1).
    Go to context

Table 1 Patient numbers and characteristics by pre-study therapy and regional distribution in the insulin detemir subgroup and entire A1chieve study population.

Demographic Insulin detemir subgroup population A1chieve study population
Global cohort Insulin-naïve Insulin- experienced Global cohort Insulin-naïve Insulin- experienced
n (%) 15,545 (100) 12,078 (77.7) 3467 (22.3) 66,726 (100) 44,872 (67.2) 21,854 (32.8)
Gender, M/F (%) 54.1/45.9 55.0/45.0 51.3/48.7 55.6/44.4 57.3/42.7 51.9/48.1
Age (years) 54.6 (11.5) 54.0 (11.3) 56.8 (11.9) 54.0 (12.0) 53.2 (11.6) 55.6 (12.5)
Body weight (kg) 76.6 (16.3) 76.5 (16.3) 76.7 (16.3) 72.9 (15.0) 71.7 (14.4) 75.3 (15.9)
BMI (kg/m2) 28.2 (5.3) 28.2 (5.3) 28.4 (5.5) 27.1 (5.0) 26.7 (4.7) 27.9 (5.50
Duration of diabetes (years) 8.4 (6.0) 7.6 (5.5) 11.0 (7.0) 8.0 (19) 80 (19) 79 (20)
>2 OGLDs, n (%) 1608 (11.7) 1320 (12.1) 288 (10.2) 10,981 (20.1) 8971 (23.1) 2010 (12.7)
HbA1c (% [mmol/mol]) 9.5 (1.6) [80] 9.5 (1.6) [80] 9.3 (1.7) [78] 9.5 (1.7) [80] 9.5 (1.7) [80] 9.4 (1.8) [79]
Geographic region (% of cohort)
China 137 (100) 88 (64.2) 49 (35.8) 11,020 (100) 8206 (74.4) 2814 (25.6)
South Asia 3079 (100) 2608 (84.7) 471 (15.3) 22,447 (100) 18,067 (80.5) 4380 (19.5)
East Asia 4230 (100) 3195 (75.5) 1035 (24.5) 10,032 (100) 6594 (65.7) 3438 (34.3)
North Africa 1746 (100) 1250 (71.6) 496 (28.4) 4039 (100) 1969 (48.7) 2070 (51.3)
Middle East and Gulf 4474 (100) 3560 (79.6) 914 (20.4) 14,976 (100) 7501 (50.1) 7475 (49.9)
Latin America 643 (100) 405 (63.0) 238 (37.0) 1138 (100) 636 (55.9) 502 (44.1)
Russia 1236 (100) 972 (78.6) 264 (21.4) 3074 (100) 1899 (61.8) 1175 (38.2)

References in context

  • The majority of patients starting basal insulin or switching to insulin detemir came from the Middle East/Gulf and East Asian regions (28.8 and 27.2%, respectively) (Table 1).
    Go to context

  • The majority of patients starting basal insulin or switching to insulin detemir came from the Middle East/Gulf and East Asian regions (28.8 and 27.2%, respectively) (Table 1).
    Go to context

Data are mean (SD), unless otherwise stated.

BMI, body mass index; OGLD, oral glucose-lowering drug.

Table 2 Outcome measures by pre-study therapy in the insulin detemir subgroup and entire A1chieve study population.

Outcome measure Insulin detemir subgroup population A1chieve study population
Global cohort Insulin- naïve Insulin- experienced Global cohort Insulin- naïve Insulin- experienced
Insulin dose (U/kg/day) n 15,545 12,078 3467 66726 44872 21854
Pre-study 0.42 (0.24) 0.42 (0.24) 0.55 (0.29) 0.55 (0.29)
Baseline 0.27 (0.15) 0.24 (0.13) 0.35 (0.19) 0.44 (0.24) 0.38 (0.20) 0.55 (0.27)
Week 24 0.37 (0.20) 0.35 (0.18) 0.45 (0.24) 0.50 (0.26) 0.44 (0.22) 0.62 (0.30)
HbA1c (% [mmol/mol]) n 10,581 8459 2122 44,661 30, 369 14,292
Baseline 9.5 (1.6) [80] 9.5 (1.6) [80] 9.3 (1.7) [78] 9.5 (1.7) [80] 9.5 (1.7) [80] 9.4 (1.8) [79]
Week 24 7.5 (1.2) [58] 7.4 (1.1) [57] 7.6 (1.3) [60] 7.4 (1.1) [57] 7.4 (1.0) [57] 7.6 (1.2) [60]
Change −2.0 (1.6) [22] x EuroQol Group. EuroQol – a new facility for the measurement of health-related quality of life. Health Policy. 1990;16:199-208 −2.1 (1.6) [23] x L. Meneghini, C. Koenen, W. Weng, J.L. Selam. The usage of a simplified self-titration dosing guideline (303 Algorithm) for insulin detemir in patients with type 2 diabetes – results of the randomized, controlled PREDICTIVE 303 study. Diabetes Obes Metab. 2007;9:902-913 Crossref. −1.6 (1.7) [17] x C. Fajardo Montañana, C. Hernández Herrero, M. Rivas Fernández. Less weight gain and hypoglycaemia with once-daily insulin detemir than NPH insulin in intensification of insulin therapy in overweight Type 2 diabetes patients: the PREDICTIVE BMI clinical trial. Diabet Med. 2008;25:916-923 −2.1 (1.7) [23] x L. Meneghini, C. Koenen, W. Weng, J.L. Selam. The usage of a simplified self-titration dosing guideline (303 Algorithm) for insulin detemir in patients with type 2 diabetes – results of the randomized, controlled PREDICTIVE 303 study. Diabetes Obes Metab. 2007;9:902-913 Crossref. −2.2 (1.7) [23] x L. Meneghini, C. Koenen, W. Weng, J.L. Selam. The usage of a simplified self-titration dosing guideline (303 Algorithm) for insulin detemir in patients with type 2 diabetes – results of the randomized, controlled PREDICTIVE 303 study. Diabetes Obes Metab. 2007;9:902-913 Crossref. −1.8 (1.7) [19] x L.F. Meneghini, K.H. Rosenberg, C. Koenen, M.J. Merilainen, H.J. Lüddeke. Insulin detemir improves glycaemic control with less hypoglycaemia and no weight gain in patients with type 2 diabetes who were insulin naive or treated with NPH or insulin glargine: clinical practice experience from a German subgroup of the PREDICTIVE study. Diabetes Obes Metab. 2007;9:418-427 Crossref.
p-value <0.001 <0.001 <0.001 <0.001 <0.001 <0.001
People reaching HbA1c <7.0% n 13,190 (100.0) 10,376 (100.0) 2814 (100.0) 57,250 (100.0) 38,639 (100.0) 18,611 (100.0)
[53 mmol/mol] (%) Baseline 3.0 2.1 6.2 3.9 3.0 5.6
Week 24 31.5 31.7 30.3 31.8 32.0 31.3
FPG, pre-breakfast (mmol/L) n 10742 8560 2182 48,191 33,087 15,104
Baseline 10.9 (3.3) 11.2 (3.2) 9.9 (3.3) 10.9 (3.5) 11.2 (3.4) 10.5 (3.7)
Week 24 7.1 (2.0) 7.0 (1.9) 7.3 (2.3) 7.1 (1.9) 7.1 (1.8) 7.2 (2.2)
Change −3.9 (3.3) −4.2 (3.2) −2.6 (3.5) −3.8 (3.5) −4.1 (3.3) −3.2 (3.8)
p-value <0.001 <0.001 <0.001 <0.001 <0.001 <0.001
PPG (mmol/L), post-breakfast n 7148 5757 1391 33,742 23,334 10,408
Baseline 14.8 (4.2) 15.0 (4.2) 13.8 (4.3) 15.1 (4.4) 15.5 (4.3) 14.2 (4.5)
Week 24 9.6 (2.9) 9.5 (2.8) 9.9 (3.2) 9.7 (2.9) 9.8 (2.9) 9.7 (3.0)
Change −5.1 (4.3) −5.5 (4.2) −3.8 (4.3) −5.4 (4.5) −5.8 (4.4) −4.5 (4.6)
p-value <0.001 <0.001 <0.001 <0.001 <0.001 <0.001
Body weight (kg) n 11,934 9336 2598 50,059 33,716 16,343
Baseline 76.6 (16.3) 76.5 (16.3) 76.7 (16.3) 73.3 (14.8) 72.1 (14.3) 75.7 (15.7)
Week 24 76.2 (15.5) 76.2 (15.4) 76.0 (15.7) 73.3 (14.1) 72.2 (13.5) 75.7 (15.1)
Change −0.4 (4.0) −0.3 (4.0) −0.7 (3.6) 0.1 (3.7) 0.1 (3.7) −0.0 (3.6)
p-value <0.001 <0.001 <0.001 <0.001 <0.001 0.081
SBP (mmHg) n 11,620 9077 2543 45,285 29,595 15,690
Baseline 133.2 (16.7) 133.3 (16.7) 133.0 (16.9) 134.2 (17.8) 134.0 (17.7) 134.7 (18.0)
Week 24 128.0 (14.9) 127.9 (15.2) 128.4 (13.7) 127.9 (13.5) 127.3 (13.3) 129.0 (13.7)
Change −5.2 (17.3) −5.4 (17.7) −4.5 (15.6) −6.3 (17.1) −6.6 (17.4) −5.7 (16.6)
p-value <0.001 <0.001 <0.001 <0.001 <0.001 <0.001
Total cholesterol (mmol/L) n 5791 4529 1262 20, 293 11,994 8299
Baseline 5.3 (1.3) 5.3 (1.2) 5.2 (1.4) 5.3 (1.3) 5.4 (1.3) 5.2 (1.3)
Week 24 4.8 (1.0) 4.8 (0.9) 4.8 (1.0) 4.8 (1.0) 4.8 (1.0) 4.8 (1.0)
Change −0.5 (1.1) −0.6 (1.1) −0.4 (1.1) −0.5 (1.2) −0.6 (1.2) −0.4 (1.2)
p-value <0.001 <0.001 <0.001 <0.001 <0.001 <0.001
HDL cholesterol (mmol/L) n 4388 3418 970 17,306 10,189 7117
Baseline 1.1 (0.4) 1.1 (0.4) 1.1 (0.4) 1.1 (0.4) 1.2 (0.4) 1.1 (0.4)
Week 24 1.2 (0.4) 1.2 (0.3) 1.2 (0.4) 1.2 (0.4) 2.7 (0.4) 1.2 (0.4)
Change 0.0 (0.4) 0.0 (0.3) 0.0 (0.4) 0.1 (0.4) 0.1 (0.4) 0.0 (0.4)
p-value <0.001 <0.001 0.012 <0.001 <0.001 <0.001
LDL cholesterol (mmol/L) n 4428 3459 969 17,494 10,304 7190
Baseline 3.1 (1.0) 3.1 (1.0) 3.0 (1.0) 3.1 (1.0) 3.2 (1.0) 3.1 (1.1)
Week 24 2.7 (0.8) 2.7 (0.8) 2.7 (0.9) 2.8 (0.9) 2.7 (0.9) 2.8 (0.9)
Change −0.4 (1.0) −0.4 (1.0) −0.3 (0.9) −0.4 (1.0) −0.4 (1.0) −0.3 (0.9)
p-value <0.001 <0.001 <0.001 <0.001 <0.001 <0.001
Triglycerides (mmol/L) n 5413 4251 1162 19,856 11,672 8184
Baseline 2.1 (1.0) 2.1 (1.0) 1.9 (1.0) 2.1 (1.1) 2.1 (1.1) 2.0 (1.1)
Week 24 1.7 (0.7) 1.7 (0.7) 1.7 (0.8) 1.8 (0.7) 1.7 (0.7) 1.8 (0.7)
Change −0.3 (0.9) −0.4 (0.9) −0.2 (0.9) −0.3 (0.9) −0.4 (1.0) −0.3 (0.9)
p-value <0.001 <0.001 <0.001 <0.001 <0.001 <0.001

References in context

  • Overall, the proportion of patients reaching HbA1c<7.0% [53 mmol/mol] increased from 3.0% at baseline to 31.5% after 24 weeks; similar results were reported for the pre-study therapy subgroups (Table 2).
    Go to context

  • Overall, the proportion of patients reaching HbA1c<7.0% [53 mmol/mol] increased from 3.0% at baseline to 31.5% after 24 weeks; similar results were reported for the pre-study therapy subgroups (Table 2).
    Go to context

  • In prior insulin users, the pre-study mean insulin dose was 0.42±0.24 IU/kg/day, and 0.45±0.24 U/kg/day of insulin detemir at 24 weeks (Table 2).
    Go to context

  • Mean blood lipid profiles improved overall by −0.5±1.1 mmol/L; there was no clinically meaningful change in high-density lipoprotein (HDL) cholesterol, but low-density lipoprotein cholesterol (LDL) values fell by −0.4±1.0 mmol/L and triglycerides by −0.3±0.9 mmol/L (p<0.001) (Table 2).
    Go to context

  • Mean blood lipid profiles improved overall by −0.5±1.1 mmol/L; there was no clinically meaningful change in high-density lipoprotein (HDL) cholesterol, but low-density lipoprotein cholesterol (LDL) values fell by −0.4±1.0 mmol/L and triglycerides by −0.3±0.9 mmol/L (p<0.001) (Table 2).
    Go to context

  • Mean blood lipid profiles improved overall by −0.5±1.1 mmol/L; there was no clinically meaningful change in high-density lipoprotein (HDL) cholesterol, but low-density lipoprotein cholesterol (LDL) values fell by −0.4±1.0 mmol/L and triglycerides by −0.3±0.9 mmol/L (p<0.001) (Table 2).
    Go to context

Data are mean (SD) unless otherwise stated.

FPG, fasting plasma glucose; HDL, high-density lipoprotein; LDL, low-density lipoprotein; PPG, postprandial plasma glucose; SBP, systolic blood pressure.


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