Back to list

An observational non-interventional study of people with diabetes beginning or changed to insulin analogue therapy in non-Western countries: The A1chieve study

Philip Home, Nabil El Naggar, Mohammed Khamseh, Guillermo Gonzalez-Galvez, Chunduo Shen, Praful Chakkarwar and Wenying Yang

Diabetes Research and Clinical Practice, Issue 3, Volume 94, pages 352 - 363

Received 20 September 2011, Revised 10 October 2011, Accepted 13 October 2011, Published online Nov-2011


Article view:

3. Results

3.1. Study participants

Participant characteristics for the entire cohort and by pre-study therapy (insulin-naïve or insulin users) are given in Table 1. Use of OGLDs prior to beginning insulin analogues is given in Table 1. Prior to enrolment in the study, 58.2% of patients were being treated with OGLDs alone, 23.8% were receiving OGLD + insulin therapy, 8.1% insulin only and 9.0% no medication for diabetes.

Table 1 Participant numbers and characteristics for the entire cohort and by pre-study therapy.

Entire cohort Insulin-naϊve Prior insulin users
n (%) 66,726 (100) 44,872 (67.2) 21,854 (32.8)
Sex, M/F (%) 55.6/44.4 57.3/42.7 51.9/48.1
Age (years) 54.0 (12.0) 53.2 (11.6) 55.6 (12.5)
Body weight (kg) 72.9 (15.0) 71.7 (14.4) 75.3 (15.9)
BMI (kg/m2) 27.1 (5.0) 26.7 (4.7) 27.9 (5.5)
Diabetes duration (years) 8.0 (6.2) 6.6 (5.4) 10.8 (6.8)
HbA1c (mmol/mol) 80 (19) 80 (19) 79 (20)
HbA1c (%) 9.5 (1.7) 9.5 (1.7) 9.4 (1.8)
Prior OGLDs, n (%)
 Metformin 44,801 (82.0) 32,006 (82.4) 12,795 (81.1)
 Sulfonylureas 37,086 (67.9) 29,645 (76.3) 7441 (47.2)
 Thiazolidinediones 10,578 (19.4) 8087 (20.8) 2491 (15.8)
 One/two/>two 16,193 (29.6)/27,466 (50.3)/10,981 (20.1) 8519 (21.9)/21,372 (55.0)/8971 (23.1) 7674 (48.6)/6094 (38.6)/2010 (12.7)
Geographic region, n (%)
 China 11,020 (100) 8206 (74.4) 2814 (25.6)
 East Asia 10,032 (100) 6594 (65.7) 3438 (34.3)
 Latin America 1138 (100) 636 (55.9) 502 (44.1)
 Middle East + Gulf 14,976 (100) 7501 (50.1) 7475 (49.9)
 North Africa 4039 (100) 1969 (48.7) 2070 (51.3)
 Russia 3074 (100) 1899 (61.8) 1175 (38.2)
 South Asia 22,447 (100) 18,067 (80.5) 4380 (19.5)

References in context

  • Use of OGLDs prior to beginning insulin analogues is given in Table 1.
    Go to context

  • Use of OGLDs prior to beginning insulin analogues is given in Table 1.
    Go to context

  • The regional distribution of participants is given in Table 1.
    Go to context

Data are n (%), %, or mean (SD).

The regional distribution of participants is given in Table 1. Notable regional differences in baseline characteristics compared with the global cohort were that the majority of study participants in Russia were female (70.9%), people from Latin America and north Africa reported the longest duration of diabetes (12.0 ± 8.3 and 11.5 ± 7.2 years, respectively), and BMI was highest in the Middle East/Gulf region (30.4 ± 5.5 kg/m2) and in Russia (31.1 ± 5.3 kg/m2). Baseline HbA1c was similar in all regions, whether prior insulin-treated or not (data not shown), being highest in Latin America (85 ± 24 mmol/mol [9.9 ± 2.2%]) and lowest in south Asia (78 ± 16 mmol/mol [9.3 ± 1.4%]).

Participant characteristics were comparable between the different types of insulin analogues started (data not shown). By prior insulin therapy, insulin-experienced people were older than the insulin-naïve cohort (55.6 years vs. 53.2 years) and had a higher BMI (27.9 kg/m2 vs. 26.7 kg/m2). Baseline HbA1c was similar (79 mmol/mol vs. 80 mmol/mol [9.4% vs. 9.5%]), while diabetes duration was 10.8 years vs. 6.6 years.

The reasons given for change in therapy by treating physicians were similar across all subgroups, with the most common reasons being to improve glycaemic control (96%), reduce the risk of hypoglycaemia (31%) and reduce plasma glucose variability (30%).

Of the 66,726 patients enrolled, all 66,726 (100%) were exposed and constituted the full analysis set and the safety analysis set, while 53,002 (79.4%) constituted the efficacy analysis set (definitions above). A total of 9335 (14.0%) withdrew from the study, the most common reason being failure to maintain contact with their physician, 6170 (9.2%); 64 (0.1%) withdrew due to an ADR; and the remaining 3101 (4.6%) for a variety of other reasons. As a result, 57,391 (86.0%) people completed the study.

3.2. Entire cohort and by prior insulin usage

3.2.1. Blood glucose lowering and insulin dose

In the insulin-naïve cohort, total daily insulin dose at 24 weeks had been titrated up to 36.4 ± 20.9 U/day. In prior insulin users, pre-analogue insulin dose was 41.0 ± 22.9 U/day, total starting insulin dose was 41.0 ± 21.4 U/day and, at 24 weeks, was 46.7 ± 24.5 U/day.

Blood glucose control improved markedly and statistically significantly between baseline and 6 months in the whole cohort (Table 2: HbA1c −23 mmol/mol [−2.1%], FPG −3.8 mmol/L, PPPG −5.4 mmol/L), and was clinically similar in the insulin-naïve and prior insulin use groups, although numerically larger in the insulin-naïve group (Table 2). Overall, the percentage of participants achieving an HbA1c level of <53 mmol/mol (<7.0%) increased from 3.9% at baseline to 31.8% at week 24.

Table 2 Glucose control and body weight for the entire cohort and by pre-study therapy at baseline and after 24 weeks of insulin analogue therapy.

Entire cohort Insulin-naϊve Prior insulin users
Baseline 24 weeks Baseline 24 weeks Baseline 24 weeks
HbA1c, mmol/mol/% n 44,661 30,369 14,292
Baseline/24 weeks 80 (19)/9.5 (1.7) 57 (12)/7.4 (1.1) 80 (19)/9.5 (1.7) 57 (11)/7.4 (1.0) 79 (20)/9.4 (1.8) 60 (13)/7.6 (1.2)
Change, p −23 (19)/−2.1 (1.7), <0.001 −23 (19)/−2.2 (1.7), <0.001 −19 (19)/−1.8 (1.7), <0.001
FPG, mmol/L n 48,191 33,087 15,104
Baseline/24 weeks 10.9 (3.5) 7.1 (1.9) 11.2 (3.4) 7.1 (1.8) 10.5 (3.7) 7.2 (2.2)
Change, p −3.8 (3.5), <0.001 −4.1 (3.3), <0.001 −3.2 (3.8), <0.001
PPPG, mmol/L n 33,742 23,334 10,408
Baseline/24 weeks 15.1 (4.4) 9.7 (2.9) 15.5 (4.3) 9.8 (2.9) 14.2 (4.5) 9.7 (3.0)
Change, p −5.4 (4.5), <0.001 −5.8 (4.4), <0.001 −4.5 (4.6), <0.001
Weight, kg n 50,059 33,716 16,343
Baseline/24 weeks 73.3 (14.8) 73.3 (14.1) 72.1 (14.3) 72.2 (13.5) 75.7 (15.7) 75.7 (15.1)
Change, p 0.1 (3.7), <0.001 0.1 (3.7), <0.001 −0.0 (3.6), 0.081
SBP, mmHg n 45,285 29,595 15,690
Baseline/24 weeks 134.2 (17.8) 127.9 (13.5) 134.0 (17.7) 127.3 (13.3) 134.7 (18.0) 129.0 (13.7)
Change, p −6.3 (17.1), <0.001 −6.6 (17.4), <0.001 −5.7 (16.6), <0.001
Total cholesterol, mmol/L n 20,293 11,994 8299
Baseline/24 weeks 5.3 (1.3) 4.8 (1.0) 5.4 (1.3) 4.8 (1.0) 5.2 (1.3) 4.8 (1.0)
Change, p −0.5 (1.2), <0.001 −0.6 (1.2), <0.001 −0.4 (1.2), <0.001
Triglycerides, mmol/L n 19,856 11,672 8184
Baseline/24 weeks 2.1 (1.1) 1.8 (0.7) 2.1 (1.1) 1.7 (0.7) 2.0 (1.1) 1.8 (0.7)
Change, p −0.3 (0.9), <0.001 −0.4 (1.0), <0.001 −0.3 (0.9), <0.001
HDL cholesterol, mmol/L n 17,306 10,189 7117
Baseline/24 weeks 1.1 (0.4) 1.2 (0.4) 1.2 (0.4) 1.2 (0.4) 1.1 (0.4) 1.2 (0.4)
Change, p 0.1 (0.4), <0.001 0.1 (0.4), <0.001 0.0 (0.4), <0.001
LDL cholesterol, mmol/L n 17,494 10,304 7190
Baseline/24 weeks 3.1 (1.0) 2.8 (0.9) 3.2 (1.0) 2.7 (0.9) 3.1 (1.1) 2.8 (0.9)
Change, p −0.4 (1.0), <0.001 −0.4 (1.0), <0.001 −0.3 (1.1), <0.001
Hypoglycaemia (event per person-year/percent with event)
 Overall Baseline/24 weeks 3.11/8.9 1.61/5.9 1.07/4.2 1.19/4.4 7.31/18.4 2.48/8.9
ap <0.0001 0.1713 <0.0001
 Minor Baseline/24 weeks 2.79/8.5 1.60/5.8 0.98/4.0 1.18/4.4 6.50/17.6 2.47/8.9
ap <0.0001 0.0056 <0.0001
 Nocturnal Baseline/24 weeks 0.93/4.0 0.36/1.8 0.28/1.6 0.26/1.3 2.24/9.0 0.58/2.9
ap <0.0001 0.0012 <0.0001
 Major Baseline/24 weeks 0.33/1.5 0.01/0.03 0.09/0.5 0.00/0.02 0.81/3.5 0.01/0.07
ap <0.0001 <0.0001 <0.0001

References in context

  • Blood glucose control improved markedly and statistically significantly between baseline and 6 months in the whole cohort (Table 2: HbA1c −23mmol/mol [−2.1%], FPG −3.8mmol/L, PPPG −5.4mmol/L), and was clinically similar in the insulin-naïve and prior insulin use groups, although numerically larger in the insulin-naïve group (Table 2).
    Go to context

  • Blood glucose control improved markedly and statistically significantly between baseline and 6 months in the whole cohort (Table 2: HbA1c −23mmol/mol [−2.1%], FPG −3.8mmol/L, PPPG −5.4mmol/L), and was clinically similar in the insulin-naïve and prior insulin use groups, although numerically larger in the insulin-naïve group (Table 2).
    Go to context

  • The reported rate of all hypoglycaemic episodes in the 4 weeks before study visits differed for the insulin-naϊve and prior insulin use cohorts (Table 2).
    Go to context

  • On pre-study therapy, major hypoglycaemic episodes were more frequent in the prior insulin use population (0.81 events/person-year) than in the insulin-naïve population (0.09 events/person-year at baseline), and reported incidence in the prior insulin users reduced to <0.01 events/person-year after 24 weeks (Table 2, people affected p<0.0001).
    Go to context

  • For both the entire cohort and the insulin-naïve population, mean body weight change over 24 weeks was statistically but not clinically significant (Table 2, mean +0.1kg, p<0.001).
    Go to context

  • Results were similar for the insulin-naϊve and prior insulin use populations (Table 2).
    Go to context

  • Results were similar for the insulin-naϊve and prior insulin use populations (Table 2).
    Go to context

  • Although people previously managed on lifestyle therapy alone or with OGLDs seemingly experienced greater improvements in glucose control than prior insulin users (Table 2), their baseline levels tended to be higher.
    Go to context

Data are mean (SD), n or incidence.

a p-value is for difference in percent of people with at least one event.

OGLD usage while starting people on insulin showed that metformin was continued in around 78% of people, for all insulin regimens. While most people starting basal insulin continued using sulfonylureas (79%), 55% or less continued using sulfonylureas with other regimens. Approximately 50% of those using a thiazolidinedione discontinued this on all regimens. Metformin use remained unchanged in people transferring insulin regimen at the start of the study. Sulfonylurea use was continued by 90% of people changing to basal insulin therapy use but discontinued by 40% of the cohort transferring to other regimens. Thiazolidinedione use continued in 70% of prior insulin users. Overall, the percentage of people who were being treated with more than two OGLDs before starting any insulin regimen was reduced by 68% (23.1% pre-study, 7.3% baseline, 7.1% end of study) and by 50% in people changing insulin therapy (12.7, 6.3 and 6.6% respectively).

3.2.2. Hypoglycaemia

The reported rate of all hypoglycaemic episodes in the 4 weeks before study visits differed for the insulin-naϊve and prior insulin use cohorts (Table 2). In the insulin-naïve population reported rates of overall hypoglycaemia increased marginally from 1.07 to 1.19 events/person-year, with no statistical difference in the proportion of people having an event. In the prior insulin users, the reported rate decreased from 7.31 to 2.48 events/person-year before the end of the study, associated with a statistically significant fall (p < 0.0001) in the number of people affected. The rate of minor hypoglycaemic events increased in the insulin-naïve cohort, from 0.98 to 1.18 events/person-year (people affected p = 0.0056), but the rate of nocturnal hypoglycaemia was clinically unchanged (0.28 vs. 0.26 events/person-year). In the prior insulin use cohort, the incidence of minor and nocturnal events decreased from 6.50 to 2.47 and 2.24 to 0.58 events/person-year (people affected both p < 0.0001), respectively, during the study period.

On pre-study therapy, major hypoglycaemic episodes were more frequent in the prior insulin use population (0.81 events/person-year) than in the insulin-naïve population (0.09 events/person-year at baseline), and reported incidence in the prior insulin users reduced to <0.01 events/person-year after 24 weeks (Table 2, people affected p < 0.0001).

3.2.3. Body weight, blood lipids and blood pressure control

For both the entire cohort and the insulin-naïve population, mean body weight change over 24 weeks was statistically but not clinically significant (Table 2, mean +0.1 kg, p < 0.001). No change in weight occurred in the prior insulin users.

Total cholesterol levels were reduced in the entire cohort from a mean of 5.3 mmol/L to 4.8 mmol/L after 24 weeks (Table 2, −0.5 mmol/L, p < 0.001). Low-density lipoprotein (LDL) cholesterol levels fell from a mean of 3.1 mmol/L to 2.8 mmol/L after 24 weeks (−0.4 mmol/L, p < 0.001), and a significant reduction was also seen in triglyceride levels (−0.3 mmol/L, p < 0.001). There was a small increase in HDL cholesterol levels during the study (+0.1 mmol/L, p < 0.001). Results were similar for the insulin-naϊve and prior insulin use populations (Table 2).

SBP fell significantly in the entire cohort, from a mean of 134 to 128 mmHg after 24 weeks of treatment (−6.3 mmHg; p < 0.001). The absolute levels at baseline and 24 weeks, and the change between these times, were very similar for the prior insulin use and insulin-naϊve populations.

3.2.4. SADRs and serious adverse events

In total, 39 SADRs were reported by 36 participants after beginning insulin analogues (0.13 events/100 patient-years). Of these, 28 people suffered a hypoglycaemic SADR. Four participants were reported to have had a serious hyperglycaemic event, one inadequate control, and ketoacidosis was observed in two people.

During the study, 214 participants had 259 serious adverse events (SAEs; 0.84 events/100 patient-years). The largest class reported was of metabolism and nutrition disorders (51 events in 50 people), of which hypoglycaemia accounted for the majority (31 events in 30 patients). The incidence of cardiac disorders was second highest with 44 events in 40 patients. Out of the total 259 SAEs, 63 events had fatal outcomes.

3.3. Insulin regimens

3.3.1. Insulin dose

In the insulin-naïve populations, starting insulin dose (0 weeks) was lowest when insulin detemir was begun (18.0 U/day), and increased to 26.7 U/day at 24 weeks (Table 3). However, even smaller increases in insulin dose (none at all for aspart alone) were seen for the other insulin regimens, although from higher baseline doses. Overall insulin use was higher in those started on insulin aspart plus basal insulin. In the insulin-experienced population, pre-study insulin dose appeared to be lower in the population starting insulin detemir, which seemingly accounts for this group having the lowest daily dose at 24 weeks (Table 3). In all groups, however, the insulin doses were 10–20% higher at 24 weeks than prior or starting insulin doses. Pre-study insulin dose was highest in patients switching to an aspart + basal insulin regimen (51.8 U/day). After 24 weeks treated with an insulin analogue, the dose was 63.3 U/day.

Table 3 Baseline and 24-week data for effectiveness and safety outcomes by insulin analogue regimen started.

Insulin-naïve Prior insulin users
Biphasic aspart Insulin detemir Insulin aspart alone Insulin aspart + basal Biphasic aspart Insulin detemir Insulin aspart alone Insulin aspart + basal
Insulin dose, U/day n 27,591 12,078 2751 1593 13,318 3467 1145 2512
Pre-study 40.5 (21.3) 31.8 (19.7) 35.1 (18.9) 51.8 (26.1)
Baseline 28.9 (12.4) 18.0 (9.9) 27.7 (12.0) 43.0 (17.7) 40.6 (18.7) 26.7 (15.1) 30.0 (15.9) 56.6 (22.9)
Week 24 32.6 (16.1) 26.7 (15.1) 27.7 (12.7) 47.0 (23.0) 45.6 (21.8) 34.4 (20.1) 36.9 (19.9) 63.3 (27.9)
HbA1c, mmol/mol/% n 18,459 8459 1764 1127 8574 2122 709 1869
Baseline 80 (19)/9.5 (1.7) 80 (18)/9.5 (1.6) 81 (20)/9.6 (1.8) 87 (23)/10.1 (2.1) 79 (20)/9.4 (1.8) 78 (19)/9.3 (1.7) 77 (21)/9.2 (1.9) 79 (20)/9.4 (1.8)
Week 24 56 (11)/7.3 (1.0) 57 (12)/7.4 (1.1) 56 (11)/7.3 (1.0) 56 (13)/7.3 (1.2) 58 (13)/7.5 (1.2) 60 (14)/7.6 (1.3) 58 (13)/7.5 (1.2) 58 (13)/7.5 (1.2)
Change, p −24 (19)/−2.2 (1.7) <0.001 −23 (18)/−2.1 (1.6) <0.001 −25 (20)/−2.3 (1.8) <0.001 −51 (22)/−2.8 (2.0) <0.001 −20 (19)/−1.8 (1.7) <0.001 − 38 (19)/−1.6 (1.7) <0.001 − 19 (21)/−1.7 (1.9) <0.001 −22 (19)/−2.0 (1.7) <0.001
FPG, mmol/L n 20,678 8560 2029 1221 9206 2182 774 1905
Baseline 11.1 (3.4) 11.2 (3.2) 11.4 (4.0) 11.9 (4.1) 10.6 (3.8) 9.9 (3.3) 10.1 (3.6) 10.3 (3.5)
Week 24 7.1 (1.8) 7.0 (1.9) 7.6 (2.2) 7.0 (1.7) 7.3 (2.2) 7.3 (2.3) 7.3 (2.2) 7.0 (1.9)
Change, p −4.0 (3.3) <0.001 −4.2 (3.2) <0.001 −3.8 (3.3) <0.001 −4.9 (4.2) <0.001 −3.3 (3.9) <0.001 −2.6 (3.5) <0.001 −2.7 (3.6) <0.001 −3.3 (3.6) <0.001
PPPG, mmol/L n 14,642 5757 1559 917 6169 1391 599 1447
Baseline 15.6 (4.2) 15.0 (4.2) 16.5 (5.0) 15.7 (5.0) 14.3 (4.5) 13.8 (4.3) 13.9 (4.6) 13.8 (4.5)
Week 24 9.8 (2.8) 9.5 (2.8) 10.6 (3.6) 9.0 (2.3) 9.8 (3.0) 9.9 (3.2) 10.3 (3.2) 8.8 (2.3)
Change, p −5.8 (4.4) <0.001 −5.5 (4.2) <0.001 −5.8 (4.3) <0.001 −6.7 (5.0) <0.001 −4.5 (4.5) <0.001 −3.8 (4.3) <0.001 −3.6 (4.3) <0.001 −4.9 (4.5) <0.001
Body weight, kg n 20,446 9336 2052 1273 9748 2598 862 2030
Baseline 70.2 (12.6) 76.5 (16.3) 68.2 (12.0) 74.7 (16.9) 74.7 (14.9) 76.7 (16.3) 70.1 (14.0) 79.7 (17.1)
Week 24 70.5 (12.0) 76.2 (15.4) 68.4 (11.4) 74.6 (15.5) 74.9 (14.5) 76.0 (15.7) 70.2 (13.4) 79.4 (16.0)
Change, p 0.3 (3.5) <0.001 −0.3 (4.0) <0.001 0.2 (2.8) 0.007 −0.0 (4.2) 0.687 0.2 (3.6) <0.001 −0.7 (3.6) <0.001 −0.0 (4.2) 0.687 −0.3 (3.7) <0.001
SBP, mmHg n 17,025 9077 1660 1268 9222 2543 765 2062
Baseline 134.1 (17.8) 133.3 (16.7) 135.8 (20.9) 133.7 (18.1) 135.4 (18.2) 133.0 (16.9) 133.6 (17.4) 133.7 (17.9)
Week 24 126.9 (12.2) 127.9 (15.2) 127.1 (12.5) 127.6 (12.6) 129.3 (13.8) 128.4 (13.7) 127.6 (14.8) 129.0 (13.1)
Change, p −7.1 (17.0) <0.001 −5.4 (17.7) <0.001 −8.7 (19.6) <0.001 −6.1 (15.7) <0.001 −6.1 (17.0) <0.001 −4.5 (15.6) <0.001 −6.0 (16.1) <0.001 −4.8 (15.3) <0.001
Total cholesterol, mmol/L n 6111 4529 457 618 4900 1262 301 1239
Baseline 5.4 (1.2) 5.3 (1.2) 5.1 (1.3) 5.6 (1.5) 5.2 (1.3) 5.2 (1.4) 5.2 (1.3) 5.3 (1.3)
Week 24 4.8 (1.0) 4.8 (0.9) 4.6 (1.0) 4.9 (1.0) 4.8 (1.0) 4.8 (1.0) 4.7 (1.0) 4.9 (1.0)
Change, p −0.6 (1.2) <0.001 −0.6 (1.1) <0.001 −0.5 (1.3) <0.001 −0.7 (1.3) <0.001 −0.4 (1.2) <0.001 −0.4 (1.1) <0.001 −0.5 (1.1) <0.001 −0.4 (1.1) <0.001
Trigylceride, mmol/L n 6086 4251 471 582 4910 1162 303 1190
Baseline 2.1 (1.1) 2.1 (1.0) 2.0 (1.1) 2.2 (1.2) 2.1 (1.1) 1.9 (1.0) 2.0 (1.0) 2.0 (1.0)
Week 24 1.8 (0.7) 1.7 (0.7) 1.8 (0.8) 1.7 (0.7) 1.8 (0.7) 1.7 (0.8) 1.8 (0.7) 1.8 (0.7)
Change, p −0.4 (1.0) <0.001 −0.4 (0.9) <0.001 −0.3 (1.0) <0.001 −0.5 (1.0) <0.001 −0.3 (1.0) <0.001 −0.2 (0.9) <0.001 −0.2 (0.7) <0.001 −0.3 (0.9) <0.001
HDL cholesterol, mmol/L n 5589 3418 439 488 4373 970 264 936
Baseline 1.2 (0.4) 1.1 (0.4) 1.1 (0.3) 1.2 (0.5) 1.1 (0.4) 1.1 (0.4) 1.2 (0.4) 1.1 (0.5)
Week 24 1.3 (0.4) 1.2 (0.3) 1.2 (0.4) 1.3 (0.4) 1.2 (0.4) 1.2 (0.4) 1.2 (0.3) 1.2 (0.4)
Change, p 0.1 (0.4) <0.001 0.0 (0.3) <0.001 0.1 (0.4) <0.001 0.1 (0.4) <0.001 0.0 (0.4) <0.001 0.0 (0.4) 0.012 0.0 (0.3) 0.826 0.1 (0.4) <0.001
LDL cholesterol, mmol/L n 5648 3459 447 495 4437 969 272 927
Baseline 3.2 (1.0) 3.1 (1.0) 3.0 (1.0) 3.3 (1.1) 3.1 (1.1) 3.0 (1.0) 3.1 (1.0) 3.0 (1.0)
Week 24 2.8 (0.9) 2.7 (0.8) 2.8 (1.0) 2.8 (0.8) 2.8 (0.9) 2.7 (0.9) 2.8 (0.9) 2.7 (0.9)
Change, p −0.4 (1.0) <0.001 −0.4 (1.0) <0.001 −0.3 (1.0) <0.001 −0.5 (1.0) <0.001 −0.3 (1.1) <0.001 −0.3 (0.9) <0.001 −0.3 (1.1) <0.001 −0.3 (1.0) <0.001
Hypoglycaemia (event per person-year/percent with event)
 Overall Baseline 0.95/4.0 1.14/4.1 1.59/5.9 1.66/5.4 5.49/15.4 8.30/20.7 6.95/18.1 14.50/29.0
Week 24 1.04/4.2 1.33/4.4 0.88/3.0 2.95/8.7 2.35/8.8 1.83/6.4 1.82/7.4 4.08/12.9
ap 0.1886 0.1982 <0.0001 0.0004 <0.0001 <0.0001 <0.0001 <0.0001
 Minor Baseline 0.86/3.8 1.06/3.9 1.46/5.6 1.50/5.4 4.96/14.9 7.42/19.7 6.02/16.8 13.10/27.9
Week 24 1.04/4.2 1.33/4.4 0.88/3.0 2.95/8.7 2.34/8.7 1.83/6.4 1.82/7.4 4.08/12.8
ap 0.0113 0.0669 <0.0001 0.0004 <0.0001 <0.0001 <0.0001 <0.0001
 Nocturnal Baseline 0.27/1.4 0.27/1.5 0.46/2.8 0.37/1.8 1.60/6.9 2.79/11.2 2.00/8.7 4.54/15.1
Week 24 0.20/1.1 0.38/1.7 0.15/0.9 0.42/2.4 0.55/2.9 0.47/1.9 0.33/1.8 0.95/5.0
ap 0.0007 0.3078 <0.0001 0.3083 <0.0001 <0.0001 <0.0001 <0.0001
 Major Baseline 0.09/0.5 0.07/0.4 0.13/0.08 0.16/0.6 0.53/2.6 0.88/3.6 0.93/4.0 1.42/6.2
Week 24 0.00/0.02 0.00/0.01 0.00/0.0 0.00/0.0 0.02/0.07 0.01/0.07 0.00/0.0 0.001/0.05
ap <0.0001 <0.0001 <0.0001 0.0022 <0.0001 <0.0001 <0.0001 <0.0001

References in context

  • In the insulin-experienced population, pre-study insulin dose appeared to be lower in the population starting insulin detemir, which seemingly accounts for this group having the lowest daily dose at 24 weeks (Table 3).
    Go to context

  • In the insulin-experienced population, pre-study insulin dose appeared to be lower in the population starting insulin detemir, which seemingly accounts for this group having the lowest daily dose at 24 weeks (Table 3).
    Go to context

  • This pattern was echoed for both FPG and PPPG control, where, again, there was no obvious differential effect of insulin type between these pre- and post-meal measures, although, again, the biggest improvements were in the insulin-naϊve populations (Table 3).
    Go to context

  • This pattern was echoed for both FPG and PPPG control, where, again, there was no obvious differential effect of insulin type between these pre- and post-meal measures, although, again, the biggest improvements were in the insulin-naϊve populations (Table 3).
    Go to context

  • In general, the changes in nocturnal hypoglycaemia tended to echo those of the overall change (Table 3).
    Go to context

  • In general, the changes in nocturnal hypoglycaemia tended to echo those of the overall change (Table 3).
    Go to context

  • The same was true of LDL cholesterol, while HDL cholesterol was unchanged with all regimens in both populations (Table 3).
    Go to context

  • The same was true of LDL cholesterol, while HDL cholesterol was unchanged with all regimens in both populations (Table 3).
    Go to context

  • The same was true of LDL cholesterol, while HDL cholesterol was unchanged with all regimens in both populations (Table 3).
    Go to context

Data are mean (SD) unless otherwise stated. A small number of people using other insulin regimens (n = 2146) could not be included in the above classifications.

a p-value is for difference in percent of people with at least one event.

3.3.2. Blood glucose control including hypoglycaemia

Clinically meaningful improvements in overall blood glucose control were found with all insulin regimens in both the insulin-naϊve and insulin-experienced populations, but were larger for all insulin analogues in the insulin-naϊve population (Table 3). For both populations, the regimen giving the biggest improvements was insulin aspart + basal insulin (as above, the groups with the highest insulin doses). This pattern was echoed for both FPG and PPPG control, where, again, there was no obvious differential effect of insulin type between these pre- and post-meal measures, although, again, the biggest improvements were in the insulin-naϊve populations (Table 3).

When HbA1c change from baseline was analysed using ANCOVA with regimen, region, sex, smoking status and pre-study therapy as factors, and age, BMI, duration of diabetes and baseline HbA1c as covariates, significant differences in HbA1c reduction were found between insulin aspart + basal insulin compared with all other regimens (p < 0.001).

In the insulin-naϊve cohort, reported overall hypoglycaemia moved erratically by insulin regimen, increasing most with the combined insulin regimen (people affected p < 0.0001), and not at all with insulin aspart alone (Table 3). For prior insulin users, reported hypoglycaemia fell markedly from the 4 weeks before baseline to the same period before 24 weeks (people affected all p < 0.0001), an effect greatest for those using insulin detemir. Major hypoglycaemia was reported too infrequently towards the end of study to do further analyses. In general, the changes in nocturnal hypoglycaemia tended to echo those of the overall change (Table 3).

3.3.3. Body weight, lipid profile and blood pressure

Changes in body weight in the study (small reductions in all groups and with all insulin regimens, Table 3) were very consistent between insulins. The same was true for the reduction in SBP, which echoed that of the entire cohort for all insulins (Table 3). Reductions in serum triglycerides were also very similar between insulin regimens, although slightly different between insulin-naϊve and non-naϊve populations. The same was true of LDL cholesterol, while HDL cholesterol was unchanged with all regimens in both populations (Table 3).

3.4. Regional differences

3.4.1. Insulin doses

There were differences in starter insulin doses between regions, with the Middle East/Gulf being highest at around 42 U/day and South and East Asia being lowest (26 and 27 U/day, respectively) (Table 4). This pattern was exaggerated at 24 weeks, when the Middle East/Gulf region had increased to a mean of 53 U/day but there was little change in South Asia (26 U/day) or in China (increasing only from 31 to 32 U/day).

Table 4 Glucose control and body weight by global region at baseline and after 24 weeks of insulin analogue therapy.

China South Asia East Asia North Africa Middle East + Gulf Latin America Russia
Dose, U/day n 11,013 22,415 10,031 4033 14,896 1136 3074
Baseline 31.0 (12.5) 26.4 (11.5) 27.1 (16.6) 32.2 (21.0) 42.3 (23.4) 31.8 (20.9) 29.5 (18.5)
Week 24 32.0 (12.8) 26.1 (11.5) 33.3 (18.0) 41.8 (23.4) 52.7 (25.0) 41.3 (24.1) 44.4 (21.7)
HbA1c, mmol/mol/% n 5784 17,111 4167 2601 11,618 573 2807
Baseline 80 (25)/9.5 (2.3) 78 (16)/9.3 (1.4) 83 (21)/9.7 (1.9) 80 (20)/9.5 (1.8) 81 (19)/9.6 (1.7) 85 (24)/9.9 (2.2) 81 (19)/9.6 (1.7)
Week 24 53 (11)/7.0 (1.0) 57 (10)/7.4 (0.9) 62 (16)/7.8 (1.4) 63 (16)/7.9 (1.4) 57 (12)/7.4 (1.1) 62 (16)/7.8 (1.4) 57 (11)/7.4 (1.0)
Change −28 (24)/−2.5 (2.2) −21 (16)/−1.9 (1.4) −22 (22)/−2.0 (2.0) −18 (21)/−1.6 (1.9) −24 (18)/−2.2 (1.6) − 24 (24)/−2.2 (2.2) −24 (17)/−2.2 (1.5)
p <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001
FPG, mmol/L n 8281 17,287 5225 2904 10,737 738 3019
Baseline 10.3 (3.6) 10.9 (3.0) 11.5 (4.3) 11.4 (4.2) 11.3 (3.7) 11.6 (4.6) 10.4 (2.7)
Week 24 6.8 (1.3) 7.3 (1.9) 7.3 (2.4) 7.9 (2.8) 7.0 (1.9) 7.2 (2.4) 6.6 (1.3)
Change −3.5 (3.7) −3.6 (2.7) −4.2 (4.5) −3.5 (4.7) −4.3 (3.6) −4.4 (4.7) −3.8 (2.7)
p <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001
PPPG, mmol/L n 6251 12,570 2987 1683 7588 146 2517
Baseline 14.2 (4.9) 15.9 (3.7) 15.8 (5.0) 14.8 (4.7) 15.4 (4.6) 15.3 (5.7) 12.1 (3.1)
Week 24 8.8 (1.9) 10.8 (3.2) 9.6 (3.3) 10.4 (3.5) 9.2 (2.4) 9.0 (2.5) 8.0 (1.4)
Change −5.4 (5.0) −5.1 (3.8) −6.1 (5.5) −4.4 (5.5) −6.2 (4.5) −6.3 (5.7) −4.2 (3.0)
p <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001
Body weight, kg n 7815 16,869 6831 3202 11,357 964 3021
Baseline 68.6 (11.5) 68.9 (10.2) 64.0 (12.3) 75.4 (13.3) 84.4 (15.4) 77.9 (16.9) 85.2 (15.6)
Week 24 68.9 (11.0) 68.9 (9.7) 64.7 (11.7) 76.2 (12.8) 84.0 (14.4) 78.1 (16.4) 84.4 (14.9)
Change 0.3 (3.1) 0.0 (3.2) 0.7 (3.8) 0.9 (3.9) −0.4 (4.4) 0.2 (4.1) −0.8 (3.3)
p <0.001 0.569 <0.001 <0.001 <0.001 0.083 <0.001
SBP, mmHg n 6414 12,739 6784 3070 12,295 954 3029
Baseline 132.4 (16.8) 135.3 (18.4) 130.1 (17.3) 133.1 (18.2) 134.9 (17.3) 130.0 (16.9) 142.4 (17.1)
Week 24 128.2 (12.4) 126.5 (11.1) 125.5 (14.9) 131.0 (19.2) 128.5 (13.2) 127.5 (14.0) 133.4 (12.3)
Change, p −4.2 (15.8) <0.001 −8.8 (16.9) <0.001 −4.6 (18.0) <0.001 −2.1 (20.9) <0.001 −6.4 (16.5) <0.001 −2.6 (17.7) <0.001 −9.0 (14.1) <0.001
Total cholesterol, mmol/L n 3589 1417 2180 1532 8213 500 2862
Baseline 5.1 (1.2) 5.1 (0.9) 5.2 (1.5) 4.7 (1.2) 5.3 (1.2) 5.6 (1.6) 6.0 (1.3)
Week 24 4.6 (1.1) 4.7 (0.8) 4.6 (1.0) 4.5 (1.0) 4.7 (0.8) 5.1 (1.0) 5.5 (1.0)
Change, p −0.5 (1.3) <0.001 −0.4 (0.6) <0.001 −0.6 (1.4) <0.001 −0.2 (1.2) <0.001 −0.6 (1.1) <0.001 −0.5 (1.5) <0.001 −0.5 (1.0) <0.001
Triglycerides, mmol/L n 3532 2264 1809 1586 8171 420 2074
Baseline 2.1 (1.3) 2.1 (0.8) 2.0 (1.1) 1.7 (0.9) 2.2 (1.0) 2.4 (1.3) 2.1 (1.0)
Week 24 1.7 (0.8) 1.8 (0.6) 1.6 (0.8) 1.5 (0.7) 1.8 (0.7) 1.9 (0.9) 1.7 (0.8)
Change, p −0.3 (1.2) <0.001 −0.3 (0.6) <0.001 −0.3 (1.0) <0.001 −0.1 (0.9) <0.001 −0.4 (0.9) <0.001 −0.5 (1.3) <0.001 −0.3 (0.8) <0.001
HDL cholesterol, mmol/L n 3255 2327 1565 1044 7447 344 1324
Baseline 1.2 (0.5) 1.0 (0.2) 1.2 (0.4) 1.1 (0.4) 1.1 (0.3) 1.1 (0.4) 1.4 (0.6)
Week 24 1.4 (0.5) 1.0 (0.3) 1.3 (0.3) 1.1 (0.4) 1.1 (0.3) 1.1 (0.3) 1.5 (0.5)
Change, p 0.1 (0.5) <0.001 −0.0 (0.3) 0.783 0.1 (0.4) <0.001 0.0 (0.5) 0.046 0.0 (0.3) <0.001 0.1 (0.3) <0.001 0.1 (0.5) <0.001
LDL cholesterol, mmol/L n 3313 2309 1567 1007 7630 322 1346
Baseline 3.1 (1.1) 3.1 (0.9) 3.2 (1.2) 2.9 (1.2) 3.2 (1.0) 3.1 (1.1) 3.3 (1.1)
Week 24 2.7 (1.0) 2.8 (0.7) 2.8 (0.9) 2.7 (1.1) 2.7 (0.8) 2.9 (0.8) 2.9 (1.0)
Change, p −0.4 (1.1) <0.001 −0.3 (0.7) <0.001 −0.4 (1.2) <0.001 −0.1 (1.5) 0.003 −0.4 (1.0) <0.001 −0.2 (1.1) <0.001 −0.4 (1.0) <0.001
Hypoglycaemia (event per person-year/percent with event)
 Overall Baseline 2.67/8.3 1.47/6.6 2.06/6.4 8.14/18.6 3.94/10.1 4.86/11.4 8.83/15.4
Week 24 1.75/7.4 0.26/1.4 1.37/5.0 4.09/13.6 2.1/7.6 1.17/5.0 5.44/15.3
ap 0.018 <0.001 <0.001 <0.001 <0.001 <0.001 0.943
 Minor Baseline 2.49/8.0 1.31/6.3 1.92/6.2 6.96/18.0 3.36/9.5 4.33/10.9 8.57/15.3
Week 24 1.75/7.4 0.26/1.4 1.37/5.0 4.03/13.4 2.09/7.6 1.17/5.0 5.44/15.3
ap 0.012 <0.001 <0.001 <0.001 <0.001 <0.001 0.7159
 Nocturnal Baseline 0.64/2.7 0.46/2.9 0.64/2.6 3.23/11.4 1.07/4.6 1.58/5.4 2.33/7.8
Week 24 0.3/1.7 0.05/0.3 0.28/1.3 1.26/5.3 0.57/2.9 0.19/1.1 0.89/4.3
ap <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001
 Major Baseline 0.18/0.9 0.16/1.0 0.14/0.6 1.18/5.3 0.58/2.5 0.53/1.7 0.26/1.0
Week 24 0.00/0.0 0.00/0.0 0.00/0.0 0.06/0.2 0.01/0.1 0.00/0.0 0.00/0.0
ap <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001

References in context

  • There were differences in starter insulin doses between regions, with the Middle East/Gulf being highest at around 42U/day and South and East Asia being lowest (26 and 27U/day, respectively) (Table 4).
    Go to context

  • Although baseline measure of blood glucose control were very similar between regions, the largest reductions in HbA1c were seen in China (−28mmol/mol [−2.5%]), and smallest in north Africa (−18mmol/mol [−1.6%]), but most clustered closely around the reduction for the entire cohort (Table 4).
    Go to context

  • Furthermore, in Russia the proportions of people affected (15.4% at baseline and 15.3% at 24 weeks, NS) did not reflect the event rate (Table 4).
    Go to context

  • Furthermore, in Russia the proportions of people affected (15.4% at baseline and 15.3% at 24 weeks, NS) did not reflect the event rate (Table 4).
    Go to context

  • HDL cholesterol values remained largely unchanged during the study and were similar across all regions (Table 4).
    Go to context

  • HDL cholesterol values remained largely unchanged during the study and were similar across all regions (Table 4).
    Go to context

  • Regional baseline rates of hypoglycaemia varied considerably, but all reported reductions in overall hypoglycaemia (Table 4).
    Go to context

Data are mean (SD) except for hypoglycaemia.

a p-value is for difference in percent of people with at least one event.

3.4.2. Blood glucose control including hypoglycaemia

Although baseline measure of blood glucose control were very similar between regions, the largest reductions in HbA1c were seen in China (−28 mmol/mol [−2.5%]), and smallest in north Africa (−18 mmol/mol [−1.6%]), but most clustered closely around the reduction for the entire cohort (Table 4). While north Africa also tended to have the lowest changes in FPG and PPPG, no particular pattern emerged in other regions and, in particular, there was no suggestion that fasting and postprandial improvements in control moved independently between regions.

Reductions in overall hypoglycaemia rates were reported from all regions, but reported baseline rates varied considerably by region (Table 4). Furthermore, in Russia the proportions of people affected (15.4% at baseline and 15.3% at 24 weeks, NS) did not reflect the event rate (Table 4). In other regions, the proportion of people affected fell significantly (p < 0.001, except China p = 0.018). In general, the falls in event rate were greatest in those regions with the highest baseline reported rates (north Africa and Russia).

3.4.3. Body weight, blood pressure and blood lipids

Mean body weight change was not clinically significant in any region, including China, with the greatest improvement in HbA1c (−28 mmol/mol [−2.5%]). There was no suggestion that regions with greater improvements in glucose control by any measure had greater weight gain. Indeed, the region with the highest overall weight gain (north Africa, +0.9 kg) was the region with the poorest improvement in HbA1c (−18 mmol/mol [−1.6%]). In the regional groups, reduction in SBP varied widely, although always statistically significantly, from 2 mmHg in north Africa to 9 mmHg in Russia. In Russia, at baseline SBP was 142 mmHg, the highest of all the regions. Total cholesterol levels were significantly reduced across all regions over 24 weeks. North Africa reported the smallest reduction (0.2 mmol/L) and the lowest value at baseline (4.7 mmol/L) (Table 4). Latin America had the highest total cholesterol at baseline (5.6 mmol/L) but a similar reduction, as in the other regions (0.5 mmol/L). The results for serum triglycerides and LDL cholesterol followed a similar regional pattern. HDL cholesterol values remained largely unchanged during the study and were similar across all regions (Table 4).

 
x

Table 1 Participant numbers and characteristics for the entire cohort and by pre-study therapy.

Entire cohort Insulin-naϊve Prior insulin users
n (%) 66,726 (100) 44,872 (67.2) 21,854 (32.8)
Sex, M/F (%) 55.6/44.4 57.3/42.7 51.9/48.1
Age (years) 54.0 (12.0) 53.2 (11.6) 55.6 (12.5)
Body weight (kg) 72.9 (15.0) 71.7 (14.4) 75.3 (15.9)
BMI (kg/m2) 27.1 (5.0) 26.7 (4.7) 27.9 (5.5)
Diabetes duration (years) 8.0 (6.2) 6.6 (5.4) 10.8 (6.8)
HbA1c (mmol/mol) 80 (19) 80 (19) 79 (20)
HbA1c (%) 9.5 (1.7) 9.5 (1.7) 9.4 (1.8)
Prior OGLDs, n (%)
 Metformin 44,801 (82.0) 32,006 (82.4) 12,795 (81.1)
 Sulfonylureas 37,086 (67.9) 29,645 (76.3) 7441 (47.2)
 Thiazolidinediones 10,578 (19.4) 8087 (20.8) 2491 (15.8)
 One/two/>two 16,193 (29.6)/27,466 (50.3)/10,981 (20.1) 8519 (21.9)/21,372 (55.0)/8971 (23.1) 7674 (48.6)/6094 (38.6)/2010 (12.7)
Geographic region, n (%)
 China 11,020 (100) 8206 (74.4) 2814 (25.6)
 East Asia 10,032 (100) 6594 (65.7) 3438 (34.3)
 Latin America 1138 (100) 636 (55.9) 502 (44.1)
 Middle East + Gulf 14,976 (100) 7501 (50.1) 7475 (49.9)
 North Africa 4039 (100) 1969 (48.7) 2070 (51.3)
 Russia 3074 (100) 1899 (61.8) 1175 (38.2)
 South Asia 22,447 (100) 18,067 (80.5) 4380 (19.5)

References in context

  • Use of OGLDs prior to beginning insulin analogues is given in Table 1.
    Go to context

  • Use of OGLDs prior to beginning insulin analogues is given in Table 1.
    Go to context

  • The regional distribution of participants is given in Table 1.
    Go to context

Data are n (%), %, or mean (SD).

Table 2 Glucose control and body weight for the entire cohort and by pre-study therapy at baseline and after 24 weeks of insulin analogue therapy.

Entire cohort Insulin-naϊve Prior insulin users
Baseline 24 weeks Baseline 24 weeks Baseline 24 weeks
HbA1c, mmol/mol/% n 44,661 30,369 14,292
Baseline/24 weeks 80 (19)/9.5 (1.7) 57 (12)/7.4 (1.1) 80 (19)/9.5 (1.7) 57 (11)/7.4 (1.0) 79 (20)/9.4 (1.8) 60 (13)/7.6 (1.2)
Change, p −23 (19)/−2.1 (1.7), <0.001 −23 (19)/−2.2 (1.7), <0.001 −19 (19)/−1.8 (1.7), <0.001
FPG, mmol/L n 48,191 33,087 15,104
Baseline/24 weeks 10.9 (3.5) 7.1 (1.9) 11.2 (3.4) 7.1 (1.8) 10.5 (3.7) 7.2 (2.2)
Change, p −3.8 (3.5), <0.001 −4.1 (3.3), <0.001 −3.2 (3.8), <0.001
PPPG, mmol/L n 33,742 23,334 10,408
Baseline/24 weeks 15.1 (4.4) 9.7 (2.9) 15.5 (4.3) 9.8 (2.9) 14.2 (4.5) 9.7 (3.0)
Change, p −5.4 (4.5), <0.001 −5.8 (4.4), <0.001 −4.5 (4.6), <0.001
Weight, kg n 50,059 33,716 16,343
Baseline/24 weeks 73.3 (14.8) 73.3 (14.1) 72.1 (14.3) 72.2 (13.5) 75.7 (15.7) 75.7 (15.1)
Change, p 0.1 (3.7), <0.001 0.1 (3.7), <0.001 −0.0 (3.6), 0.081
SBP, mmHg n 45,285 29,595 15,690
Baseline/24 weeks 134.2 (17.8) 127.9 (13.5) 134.0 (17.7) 127.3 (13.3) 134.7 (18.0) 129.0 (13.7)
Change, p −6.3 (17.1), <0.001 −6.6 (17.4), <0.001 −5.7 (16.6), <0.001
Total cholesterol, mmol/L n 20,293 11,994 8299
Baseline/24 weeks 5.3 (1.3) 4.8 (1.0) 5.4 (1.3) 4.8 (1.0) 5.2 (1.3) 4.8 (1.0)
Change, p −0.5 (1.2), <0.001 −0.6 (1.2), <0.001 −0.4 (1.2), <0.001
Triglycerides, mmol/L n 19,856 11,672 8184
Baseline/24 weeks 2.1 (1.1) 1.8 (0.7) 2.1 (1.1) 1.7 (0.7) 2.0 (1.1) 1.8 (0.7)
Change, p −0.3 (0.9), <0.001 −0.4 (1.0), <0.001 −0.3 (0.9), <0.001
HDL cholesterol, mmol/L n 17,306 10,189 7117
Baseline/24 weeks 1.1 (0.4) 1.2 (0.4) 1.2 (0.4) 1.2 (0.4) 1.1 (0.4) 1.2 (0.4)
Change, p 0.1 (0.4), <0.001 0.1 (0.4), <0.001 0.0 (0.4), <0.001
LDL cholesterol, mmol/L n 17,494 10,304 7190
Baseline/24 weeks 3.1 (1.0) 2.8 (0.9) 3.2 (1.0) 2.7 (0.9) 3.1 (1.1) 2.8 (0.9)
Change, p −0.4 (1.0), <0.001 −0.4 (1.0), <0.001 −0.3 (1.1), <0.001
Hypoglycaemia (event per person-year/percent with event)
 Overall Baseline/24 weeks 3.11/8.9 1.61/5.9 1.07/4.2 1.19/4.4 7.31/18.4 2.48/8.9
ap <0.0001 0.1713 <0.0001
 Minor Baseline/24 weeks 2.79/8.5 1.60/5.8 0.98/4.0 1.18/4.4 6.50/17.6 2.47/8.9
ap <0.0001 0.0056 <0.0001
 Nocturnal Baseline/24 weeks 0.93/4.0 0.36/1.8 0.28/1.6 0.26/1.3 2.24/9.0 0.58/2.9
ap <0.0001 0.0012 <0.0001
 Major Baseline/24 weeks 0.33/1.5 0.01/0.03 0.09/0.5 0.00/0.02 0.81/3.5 0.01/0.07
ap <0.0001 <0.0001 <0.0001

References in context

  • Blood glucose control improved markedly and statistically significantly between baseline and 6 months in the whole cohort (Table 2: HbA1c −23mmol/mol [−2.1%], FPG −3.8mmol/L, PPPG −5.4mmol/L), and was clinically similar in the insulin-naïve and prior insulin use groups, although numerically larger in the insulin-naïve group (Table 2).
    Go to context

  • Blood glucose control improved markedly and statistically significantly between baseline and 6 months in the whole cohort (Table 2: HbA1c −23mmol/mol [−2.1%], FPG −3.8mmol/L, PPPG −5.4mmol/L), and was clinically similar in the insulin-naïve and prior insulin use groups, although numerically larger in the insulin-naïve group (Table 2).
    Go to context

  • The reported rate of all hypoglycaemic episodes in the 4 weeks before study visits differed for the insulin-naϊve and prior insulin use cohorts (Table 2).
    Go to context

  • On pre-study therapy, major hypoglycaemic episodes were more frequent in the prior insulin use population (0.81 events/person-year) than in the insulin-naïve population (0.09 events/person-year at baseline), and reported incidence in the prior insulin users reduced to <0.01 events/person-year after 24 weeks (Table 2, people affected p<0.0001).
    Go to context

  • For both the entire cohort and the insulin-naïve population, mean body weight change over 24 weeks was statistically but not clinically significant (Table 2, mean +0.1kg, p<0.001).
    Go to context

  • Results were similar for the insulin-naϊve and prior insulin use populations (Table 2).
    Go to context

  • Results were similar for the insulin-naϊve and prior insulin use populations (Table 2).
    Go to context

  • Although people previously managed on lifestyle therapy alone or with OGLDs seemingly experienced greater improvements in glucose control than prior insulin users (Table 2), their baseline levels tended to be higher.
    Go to context

Data are mean (SD), n or incidence.

a p-value is for difference in percent of people with at least one event.

Table 3 Baseline and 24-week data for effectiveness and safety outcomes by insulin analogue regimen started.

Insulin-naïve Prior insulin users
Biphasic aspart Insulin detemir Insulin aspart alone Insulin aspart + basal Biphasic aspart Insulin detemir Insulin aspart alone Insulin aspart + basal
Insulin dose, U/day n 27,591 12,078 2751 1593 13,318 3467 1145 2512
Pre-study 40.5 (21.3) 31.8 (19.7) 35.1 (18.9) 51.8 (26.1)
Baseline 28.9 (12.4) 18.0 (9.9) 27.7 (12.0) 43.0 (17.7) 40.6 (18.7) 26.7 (15.1) 30.0 (15.9) 56.6 (22.9)
Week 24 32.6 (16.1) 26.7 (15.1) 27.7 (12.7) 47.0 (23.0) 45.6 (21.8) 34.4 (20.1) 36.9 (19.9) 63.3 (27.9)
HbA1c, mmol/mol/% n 18,459 8459 1764 1127 8574 2122 709 1869
Baseline 80 (19)/9.5 (1.7) 80 (18)/9.5 (1.6) 81 (20)/9.6 (1.8) 87 (23)/10.1 (2.1) 79 (20)/9.4 (1.8) 78 (19)/9.3 (1.7) 77 (21)/9.2 (1.9) 79 (20)/9.4 (1.8)
Week 24 56 (11)/7.3 (1.0) 57 (12)/7.4 (1.1) 56 (11)/7.3 (1.0) 56 (13)/7.3 (1.2) 58 (13)/7.5 (1.2) 60 (14)/7.6 (1.3) 58 (13)/7.5 (1.2) 58 (13)/7.5 (1.2)
Change, p −24 (19)/−2.2 (1.7) <0.001 −23 (18)/−2.1 (1.6) <0.001 −25 (20)/−2.3 (1.8) <0.001 −51 (22)/−2.8 (2.0) <0.001 −20 (19)/−1.8 (1.7) <0.001 − 38 (19)/−1.6 (1.7) <0.001 − 19 (21)/−1.7 (1.9) <0.001 −22 (19)/−2.0 (1.7) <0.001
FPG, mmol/L n 20,678 8560 2029 1221 9206 2182 774 1905
Baseline 11.1 (3.4) 11.2 (3.2) 11.4 (4.0) 11.9 (4.1) 10.6 (3.8) 9.9 (3.3) 10.1 (3.6) 10.3 (3.5)
Week 24 7.1 (1.8) 7.0 (1.9) 7.6 (2.2) 7.0 (1.7) 7.3 (2.2) 7.3 (2.3) 7.3 (2.2) 7.0 (1.9)
Change, p −4.0 (3.3) <0.001 −4.2 (3.2) <0.001 −3.8 (3.3) <0.001 −4.9 (4.2) <0.001 −3.3 (3.9) <0.001 −2.6 (3.5) <0.001 −2.7 (3.6) <0.001 −3.3 (3.6) <0.001
PPPG, mmol/L n 14,642 5757 1559 917 6169 1391 599 1447
Baseline 15.6 (4.2) 15.0 (4.2) 16.5 (5.0) 15.7 (5.0) 14.3 (4.5) 13.8 (4.3) 13.9 (4.6) 13.8 (4.5)
Week 24 9.8 (2.8) 9.5 (2.8) 10.6 (3.6) 9.0 (2.3) 9.8 (3.0) 9.9 (3.2) 10.3 (3.2) 8.8 (2.3)
Change, p −5.8 (4.4) <0.001 −5.5 (4.2) <0.001 −5.8 (4.3) <0.001 −6.7 (5.0) <0.001 −4.5 (4.5) <0.001 −3.8 (4.3) <0.001 −3.6 (4.3) <0.001 −4.9 (4.5) <0.001
Body weight, kg n 20,446 9336 2052 1273 9748 2598 862 2030
Baseline 70.2 (12.6) 76.5 (16.3) 68.2 (12.0) 74.7 (16.9) 74.7 (14.9) 76.7 (16.3) 70.1 (14.0) 79.7 (17.1)
Week 24 70.5 (12.0) 76.2 (15.4) 68.4 (11.4) 74.6 (15.5) 74.9 (14.5) 76.0 (15.7) 70.2 (13.4) 79.4 (16.0)
Change, p 0.3 (3.5) <0.001 −0.3 (4.0) <0.001 0.2 (2.8) 0.007 −0.0 (4.2) 0.687 0.2 (3.6) <0.001 −0.7 (3.6) <0.001 −0.0 (4.2) 0.687 −0.3 (3.7) <0.001
SBP, mmHg n 17,025 9077 1660 1268 9222 2543 765 2062
Baseline 134.1 (17.8) 133.3 (16.7) 135.8 (20.9) 133.7 (18.1) 135.4 (18.2) 133.0 (16.9) 133.6 (17.4) 133.7 (17.9)
Week 24 126.9 (12.2) 127.9 (15.2) 127.1 (12.5) 127.6 (12.6) 129.3 (13.8) 128.4 (13.7) 127.6 (14.8) 129.0 (13.1)
Change, p −7.1 (17.0) <0.001 −5.4 (17.7) <0.001 −8.7 (19.6) <0.001 −6.1 (15.7) <0.001 −6.1 (17.0) <0.001 −4.5 (15.6) <0.001 −6.0 (16.1) <0.001 −4.8 (15.3) <0.001
Total cholesterol, mmol/L n 6111 4529 457 618 4900 1262 301 1239
Baseline 5.4 (1.2) 5.3 (1.2) 5.1 (1.3) 5.6 (1.5) 5.2 (1.3) 5.2 (1.4) 5.2 (1.3) 5.3 (1.3)
Week 24 4.8 (1.0) 4.8 (0.9) 4.6 (1.0) 4.9 (1.0) 4.8 (1.0) 4.8 (1.0) 4.7 (1.0) 4.9 (1.0)
Change, p −0.6 (1.2) <0.001 −0.6 (1.1) <0.001 −0.5 (1.3) <0.001 −0.7 (1.3) <0.001 −0.4 (1.2) <0.001 −0.4 (1.1) <0.001 −0.5 (1.1) <0.001 −0.4 (1.1) <0.001
Trigylceride, mmol/L n 6086 4251 471 582 4910 1162 303 1190
Baseline 2.1 (1.1) 2.1 (1.0) 2.0 (1.1) 2.2 (1.2) 2.1 (1.1) 1.9 (1.0) 2.0 (1.0) 2.0 (1.0)
Week 24 1.8 (0.7) 1.7 (0.7) 1.8 (0.8) 1.7 (0.7) 1.8 (0.7) 1.7 (0.8) 1.8 (0.7) 1.8 (0.7)
Change, p −0.4 (1.0) <0.001 −0.4 (0.9) <0.001 −0.3 (1.0) <0.001 −0.5 (1.0) <0.001 −0.3 (1.0) <0.001 −0.2 (0.9) <0.001 −0.2 (0.7) <0.001 −0.3 (0.9) <0.001
HDL cholesterol, mmol/L n 5589 3418 439 488 4373 970 264 936
Baseline 1.2 (0.4) 1.1 (0.4) 1.1 (0.3) 1.2 (0.5) 1.1 (0.4) 1.1 (0.4) 1.2 (0.4) 1.1 (0.5)
Week 24 1.3 (0.4) 1.2 (0.3) 1.2 (0.4) 1.3 (0.4) 1.2 (0.4) 1.2 (0.4) 1.2 (0.3) 1.2 (0.4)
Change, p 0.1 (0.4) <0.001 0.0 (0.3) <0.001 0.1 (0.4) <0.001 0.1 (0.4) <0.001 0.0 (0.4) <0.001 0.0 (0.4) 0.012 0.0 (0.3) 0.826 0.1 (0.4) <0.001
LDL cholesterol, mmol/L n 5648 3459 447 495 4437 969 272 927
Baseline 3.2 (1.0) 3.1 (1.0) 3.0 (1.0) 3.3 (1.1) 3.1 (1.1) 3.0 (1.0) 3.1 (1.0) 3.0 (1.0)
Week 24 2.8 (0.9) 2.7 (0.8) 2.8 (1.0) 2.8 (0.8) 2.8 (0.9) 2.7 (0.9) 2.8 (0.9) 2.7 (0.9)
Change, p −0.4 (1.0) <0.001 −0.4 (1.0) <0.001 −0.3 (1.0) <0.001 −0.5 (1.0) <0.001 −0.3 (1.1) <0.001 −0.3 (0.9) <0.001 −0.3 (1.1) <0.001 −0.3 (1.0) <0.001
Hypoglycaemia (event per person-year/percent with event)
 Overall Baseline 0.95/4.0 1.14/4.1 1.59/5.9 1.66/5.4 5.49/15.4 8.30/20.7 6.95/18.1 14.50/29.0
Week 24 1.04/4.2 1.33/4.4 0.88/3.0 2.95/8.7 2.35/8.8 1.83/6.4 1.82/7.4 4.08/12.9
ap 0.1886 0.1982 <0.0001 0.0004 <0.0001 <0.0001 <0.0001 <0.0001
 Minor Baseline 0.86/3.8 1.06/3.9 1.46/5.6 1.50/5.4 4.96/14.9 7.42/19.7 6.02/16.8 13.10/27.9
Week 24 1.04/4.2 1.33/4.4 0.88/3.0 2.95/8.7 2.34/8.7 1.83/6.4 1.82/7.4 4.08/12.8
ap 0.0113 0.0669 <0.0001 0.0004 <0.0001 <0.0001 <0.0001 <0.0001
 Nocturnal Baseline 0.27/1.4 0.27/1.5 0.46/2.8 0.37/1.8 1.60/6.9 2.79/11.2 2.00/8.7 4.54/15.1
Week 24 0.20/1.1 0.38/1.7 0.15/0.9 0.42/2.4 0.55/2.9 0.47/1.9 0.33/1.8 0.95/5.0
ap 0.0007 0.3078 <0.0001 0.3083 <0.0001 <0.0001 <0.0001 <0.0001
 Major Baseline 0.09/0.5 0.07/0.4 0.13/0.08 0.16/0.6 0.53/2.6 0.88/3.6 0.93/4.0 1.42/6.2
Week 24 0.00/0.02 0.00/0.01 0.00/0.0 0.00/0.0 0.02/0.07 0.01/0.07 0.00/0.0 0.001/0.05
ap <0.0001 <0.0001 <0.0001 0.0022 <0.0001 <0.0001 <0.0001 <0.0001

References in context

  • In the insulin-experienced population, pre-study insulin dose appeared to be lower in the population starting insulin detemir, which seemingly accounts for this group having the lowest daily dose at 24 weeks (Table 3).
    Go to context

  • In the insulin-experienced population, pre-study insulin dose appeared to be lower in the population starting insulin detemir, which seemingly accounts for this group having the lowest daily dose at 24 weeks (Table 3).
    Go to context

  • This pattern was echoed for both FPG and PPPG control, where, again, there was no obvious differential effect of insulin type between these pre- and post-meal measures, although, again, the biggest improvements were in the insulin-naϊve populations (Table 3).
    Go to context

  • This pattern was echoed for both FPG and PPPG control, where, again, there was no obvious differential effect of insulin type between these pre- and post-meal measures, although, again, the biggest improvements were in the insulin-naϊve populations (Table 3).
    Go to context

  • In general, the changes in nocturnal hypoglycaemia tended to echo those of the overall change (Table 3).
    Go to context

  • In general, the changes in nocturnal hypoglycaemia tended to echo those of the overall change (Table 3).
    Go to context

  • The same was true of LDL cholesterol, while HDL cholesterol was unchanged with all regimens in both populations (Table 3).
    Go to context

  • The same was true of LDL cholesterol, while HDL cholesterol was unchanged with all regimens in both populations (Table 3).
    Go to context

  • The same was true of LDL cholesterol, while HDL cholesterol was unchanged with all regimens in both populations (Table 3).
    Go to context

Data are mean (SD) unless otherwise stated. A small number of people using other insulin regimens (n = 2146) could not be included in the above classifications.

a p-value is for difference in percent of people with at least one event.

Table 4 Glucose control and body weight by global region at baseline and after 24 weeks of insulin analogue therapy.

China South Asia East Asia North Africa Middle East + Gulf Latin America Russia
Dose, U/day n 11,013 22,415 10,031 4033 14,896 1136 3074
Baseline 31.0 (12.5) 26.4 (11.5) 27.1 (16.6) 32.2 (21.0) 42.3 (23.4) 31.8 (20.9) 29.5 (18.5)
Week 24 32.0 (12.8) 26.1 (11.5) 33.3 (18.0) 41.8 (23.4) 52.7 (25.0) 41.3 (24.1) 44.4 (21.7)
HbA1c, mmol/mol/% n 5784 17,111 4167 2601 11,618 573 2807
Baseline 80 (25)/9.5 (2.3) 78 (16)/9.3 (1.4) 83 (21)/9.7 (1.9) 80 (20)/9.5 (1.8) 81 (19)/9.6 (1.7) 85 (24)/9.9 (2.2) 81 (19)/9.6 (1.7)
Week 24 53 (11)/7.0 (1.0) 57 (10)/7.4 (0.9) 62 (16)/7.8 (1.4) 63 (16)/7.9 (1.4) 57 (12)/7.4 (1.1) 62 (16)/7.8 (1.4) 57 (11)/7.4 (1.0)
Change −28 (24)/−2.5 (2.2) −21 (16)/−1.9 (1.4) −22 (22)/−2.0 (2.0) −18 (21)/−1.6 (1.9) −24 (18)/−2.2 (1.6) − 24 (24)/−2.2 (2.2) −24 (17)/−2.2 (1.5)
p <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001
FPG, mmol/L n 8281 17,287 5225 2904 10,737 738 3019
Baseline 10.3 (3.6) 10.9 (3.0) 11.5 (4.3) 11.4 (4.2) 11.3 (3.7) 11.6 (4.6) 10.4 (2.7)
Week 24 6.8 (1.3) 7.3 (1.9) 7.3 (2.4) 7.9 (2.8) 7.0 (1.9) 7.2 (2.4) 6.6 (1.3)
Change −3.5 (3.7) −3.6 (2.7) −4.2 (4.5) −3.5 (4.7) −4.3 (3.6) −4.4 (4.7) −3.8 (2.7)
p <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001
PPPG, mmol/L n 6251 12,570 2987 1683 7588 146 2517
Baseline 14.2 (4.9) 15.9 (3.7) 15.8 (5.0) 14.8 (4.7) 15.4 (4.6) 15.3 (5.7) 12.1 (3.1)
Week 24 8.8 (1.9) 10.8 (3.2) 9.6 (3.3) 10.4 (3.5) 9.2 (2.4) 9.0 (2.5) 8.0 (1.4)
Change −5.4 (5.0) −5.1 (3.8) −6.1 (5.5) −4.4 (5.5) −6.2 (4.5) −6.3 (5.7) −4.2 (3.0)
p <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001
Body weight, kg n 7815 16,869 6831 3202 11,357 964 3021
Baseline 68.6 (11.5) 68.9 (10.2) 64.0 (12.3) 75.4 (13.3) 84.4 (15.4) 77.9 (16.9) 85.2 (15.6)
Week 24 68.9 (11.0) 68.9 (9.7) 64.7 (11.7) 76.2 (12.8) 84.0 (14.4) 78.1 (16.4) 84.4 (14.9)
Change 0.3 (3.1) 0.0 (3.2) 0.7 (3.8) 0.9 (3.9) −0.4 (4.4) 0.2 (4.1) −0.8 (3.3)
p <0.001 0.569 <0.001 <0.001 <0.001 0.083 <0.001
SBP, mmHg n 6414 12,739 6784 3070 12,295 954 3029
Baseline 132.4 (16.8) 135.3 (18.4) 130.1 (17.3) 133.1 (18.2) 134.9 (17.3) 130.0 (16.9) 142.4 (17.1)
Week 24 128.2 (12.4) 126.5 (11.1) 125.5 (14.9) 131.0 (19.2) 128.5 (13.2) 127.5 (14.0) 133.4 (12.3)
Change, p −4.2 (15.8) <0.001 −8.8 (16.9) <0.001 −4.6 (18.0) <0.001 −2.1 (20.9) <0.001 −6.4 (16.5) <0.001 −2.6 (17.7) <0.001 −9.0 (14.1) <0.001
Total cholesterol, mmol/L n 3589 1417 2180 1532 8213 500 2862
Baseline 5.1 (1.2) 5.1 (0.9) 5.2 (1.5) 4.7 (1.2) 5.3 (1.2) 5.6 (1.6) 6.0 (1.3)
Week 24 4.6 (1.1) 4.7 (0.8) 4.6 (1.0) 4.5 (1.0) 4.7 (0.8) 5.1 (1.0) 5.5 (1.0)
Change, p −0.5 (1.3) <0.001 −0.4 (0.6) <0.001 −0.6 (1.4) <0.001 −0.2 (1.2) <0.001 −0.6 (1.1) <0.001 −0.5 (1.5) <0.001 −0.5 (1.0) <0.001
Triglycerides, mmol/L n 3532 2264 1809 1586 8171 420 2074
Baseline 2.1 (1.3) 2.1 (0.8) 2.0 (1.1) 1.7 (0.9) 2.2 (1.0) 2.4 (1.3) 2.1 (1.0)
Week 24 1.7 (0.8) 1.8 (0.6) 1.6 (0.8) 1.5 (0.7) 1.8 (0.7) 1.9 (0.9) 1.7 (0.8)
Change, p −0.3 (1.2) <0.001 −0.3 (0.6) <0.001 −0.3 (1.0) <0.001 −0.1 (0.9) <0.001 −0.4 (0.9) <0.001 −0.5 (1.3) <0.001 −0.3 (0.8) <0.001
HDL cholesterol, mmol/L n 3255 2327 1565 1044 7447 344 1324
Baseline 1.2 (0.5) 1.0 (0.2) 1.2 (0.4) 1.1 (0.4) 1.1 (0.3) 1.1 (0.4) 1.4 (0.6)
Week 24 1.4 (0.5) 1.0 (0.3) 1.3 (0.3) 1.1 (0.4) 1.1 (0.3) 1.1 (0.3) 1.5 (0.5)
Change, p 0.1 (0.5) <0.001 −0.0 (0.3) 0.783 0.1 (0.4) <0.001 0.0 (0.5) 0.046 0.0 (0.3) <0.001 0.1 (0.3) <0.001 0.1 (0.5) <0.001
LDL cholesterol, mmol/L n 3313 2309 1567 1007 7630 322 1346
Baseline 3.1 (1.1) 3.1 (0.9) 3.2 (1.2) 2.9 (1.2) 3.2 (1.0) 3.1 (1.1) 3.3 (1.1)
Week 24 2.7 (1.0) 2.8 (0.7) 2.8 (0.9) 2.7 (1.1) 2.7 (0.8) 2.9 (0.8) 2.9 (1.0)
Change, p −0.4 (1.1) <0.001 −0.3 (0.7) <0.001 −0.4 (1.2) <0.001 −0.1 (1.5) 0.003 −0.4 (1.0) <0.001 −0.2 (1.1) <0.001 −0.4 (1.0) <0.001
Hypoglycaemia (event per person-year/percent with event)
 Overall Baseline 2.67/8.3 1.47/6.6 2.06/6.4 8.14/18.6 3.94/10.1 4.86/11.4 8.83/15.4
Week 24 1.75/7.4 0.26/1.4 1.37/5.0 4.09/13.6 2.1/7.6 1.17/5.0 5.44/15.3
ap 0.018 <0.001 <0.001 <0.001 <0.001 <0.001 0.943
 Minor Baseline 2.49/8.0 1.31/6.3 1.92/6.2 6.96/18.0 3.36/9.5 4.33/10.9 8.57/15.3
Week 24 1.75/7.4 0.26/1.4 1.37/5.0 4.03/13.4 2.09/7.6 1.17/5.0 5.44/15.3
ap 0.012 <0.001 <0.001 <0.001 <0.001 <0.001 0.7159
 Nocturnal Baseline 0.64/2.7 0.46/2.9 0.64/2.6 3.23/11.4 1.07/4.6 1.58/5.4 2.33/7.8
Week 24 0.3/1.7 0.05/0.3 0.28/1.3 1.26/5.3 0.57/2.9 0.19/1.1 0.89/4.3
ap <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001
 Major Baseline 0.18/0.9 0.16/1.0 0.14/0.6 1.18/5.3 0.58/2.5 0.53/1.7 0.26/1.0
Week 24 0.00/0.0 0.00/0.0 0.00/0.0 0.06/0.2 0.01/0.1 0.00/0.0 0.00/0.0
ap <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001

References in context

  • There were differences in starter insulin doses between regions, with the Middle East/Gulf being highest at around 42U/day and South and East Asia being lowest (26 and 27U/day, respectively) (Table 4).
    Go to context

  • Although baseline measure of blood glucose control were very similar between regions, the largest reductions in HbA1c were seen in China (−28mmol/mol [−2.5%]), and smallest in north Africa (−18mmol/mol [−1.6%]), but most clustered closely around the reduction for the entire cohort (Table 4).
    Go to context

  • Furthermore, in Russia the proportions of people affected (15.4% at baseline and 15.3% at 24 weeks, NS) did not reflect the event rate (Table 4).
    Go to context

  • Furthermore, in Russia the proportions of people affected (15.4% at baseline and 15.3% at 24 weeks, NS) did not reflect the event rate (Table 4).
    Go to context

  • HDL cholesterol values remained largely unchanged during the study and were similar across all regions (Table 4).
    Go to context

  • HDL cholesterol values remained largely unchanged during the study and were similar across all regions (Table 4).
    Go to context

  • Regional baseline rates of hypoglycaemia varied considerably, but all reported reductions in overall hypoglycaemia (Table 4).
    Go to context

Data are mean (SD) except for hypoglycaemia.

a p-value is for difference in percent of people with at least one event.


Back to list