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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


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4. Discussion

The overall results from the A1chieve non-interventional observational study find that beginning therapy with the insulin analogues detemir, aspart and biphasic aspart 30 under routine clinical practice was associated with marked improvements in average blood glucose levels (as measured by HbA1c), without evident tolerability or safety issues in the short term. Indeed, given that increase in hypoglycaemia was not a problem, and body weight was essentially unchanged, improvements in HbA1c of 22 mmol/mol (2.0%) or more are remarkable, and larger than would be expected from data from most RCTs [13], [14], [15], [16], [17], [24], and [25] 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. Diabetic Med. 2008;25:916-923 x A. Philis-Tsimikas, G. Charpentier, P. Clauson, G.M. Ravn, V.L. Roberts, B. Thorsteinsson. Comparison of once-daily insulin detemir with NPH insulin added to a regimen of oral antidiabetic drugs in poorly controlled type 2 diabetes. Clin Ther. 2006;28:1569-1581 [Erratum in: Clin Ther 2006;28:1967] x K. Hermansen, M. Davies, T. Derezinski, G. Martinez Ravn, P. Clauson, P. Home. A 26-week, randomized, parallel, treat-to-target trial comparing insulin detemir with NPH insulin as add-on therapy to oral glucose-lowering drugs in insulin-naive people with type 2 diabetes. Diabetes Care. 2006;29:1269-1274 [Erratum in: Diabetes Care 2007;30:1035] x A. Liebl, R. Prager, K. Binz, M. Kaiser, R. Bergenstal, B. Gallwitz. Comparison of insulin analog regimens in people with type 2 diabetes mellitus in the PREFER Study: a randomized controlled trial. Diabetes Obes Metab. 2009;11:45-52 x L. Meneghini, H. Mersebach, S. Kumar, A.L. Svendsen, K. Hermansen. A comparison of two intensification regimens with rapid-acting insulin aspart in type 2 diabetes inadequately controlled by once-daily insulin detemir and oral antidiabetes drugs: the STEP-Wise™ randomized study. Endocr Pract. 2011;6:1-26 x B.O. Boehm, P.D. Home, C. Behrend, N.M. Kamp, A. Lindholm. Premixed insulin aspart 30 vs. premixed human insulin 30/70 twice daily: a randomized trial in type 1 and type 2 diabetic patients. Diabetic Med. 2002;19:393-399 x J.S. Christiansen, J.A. Vaz, Z. Metelko, M. Bogoev, I. Dedov. Twice daily biphasic insulin aspart improves postprandial glycaemic control more effectively than twice daily NPH insulin, with low risk of hypoglycaemia, in patients with type 2 diabetes. Diabetes Obes Metab. 2003;5:446-454 . Furthermore, these findings were reproduced in people from all the seven global regions studied, and were irrespective of the insulin regimen started, or indeed, for the most part, of whether the participants were insulin-treated at the time of starting the analogues or insulin-naïve. Although the reductions in HbA1c were large, the proportion of people then achieving a target level of <53 mmol/mol (<7.0%) was disappointing, reflecting the very poor blood glucose control at baseline, the short duration of follow-up and the limited titration of insulin doses over the 6 months of study.

That the HbA1c data are real is supported by the large and consistent reductions in FPG and PPPG control. 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. This result is not unexpected, similar findings with regard to pre-study treatment regimen having been reported in the IMPROVE observational study of 52,419 people from 11 countries with T2D starting or switching to biphasic insulin aspart as part of routine clinical care [6] x P. Valensi, M. Benroubi, V. Borzi, J. Gumprecht, R. Kawamori, J. Shaban, et al. The IMPROVE study—a multinational, observational study in type 2 diabetes: baseline characteristics from eight national cohorts. Int J Clin Pract. 2008;62:1809-1819 . Also consistent with the glucose-lowering findings are the reductions in LDL cholesterol and triglycerides, but, surprisingly, SBP was also lower, which, together with the lack of body weight gain, suggests that factors other than insulin therapy itself are contributors to the improvements in metabolic status.

The most likely factor here is improvement in lifestyle and, in particular, in nutritional intake. Body weight gain in 6 months with an HbA1c improvement of around 22 mmol/mol (2.0%) or more would be expected to be around 4 kg [26] x H. Yki-Järvinen. Combination therapies with insulin in type 2 diabetes. Diabetes Care. 2001;24:758-767 , due to amelioration of urinary glycosuria and glucose concentration-driven glucose metabolism [27] x B. Ravikumar, P.E. Carey, J.E. Snaar, D.K. Deelchand, D.B. Cook, R.D. Neely, et al. Real-time assessment of postprandial fat storage in liver and skeletal muscle in health and type 2 diabetes. Am J Physiol Endocrinol Metab. 2005;288:E789-E797 ; that this did not occur would suggest that participants and advising healthcare teams took advantage of the starting of insulin analogues to enhance self-care behaviours. This, in turn, is consistent with the improvement in blood pressure control and in the lipid profile, but the possibility remains that specific therapy changes (not recorded) could also have influenced the findings. Interestingly, the region with the numerically smallest fall in HbA1c (north Africa) was that with the numerically largest gain in weight, suggesting perhaps that, in this region, changes in self-management were less marked than elsewhere.

Overall, the large reduction in the HbA1c, FPG and PPPG levels following 24 weeks of use of these insulin analogues was associated with a low incidence of reported drug reactions (SADRs) and hypoglycaemia. While improvements in glycaemic control are usually associated with an increased risk of hypoglycaemia [28] x UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet. 1998;352:837-853 , the global cohort from this study reported a decrease in the rate of all hypoglycaemic episodes from 3.1 events/person-year at baseline to 1.6 events/person-year in the 4 weeks before the end of the study. The reduction in reported relative event rate was even more marked for major hypoglycaemic episodes. Although the percentage reduction in event rate appears high, in absolute terms it is low, consistent with other reports of hypoglycaemia in people with T2D [6], [14], and [29] x P. Valensi, M. Benroubi, V. Borzi, J. Gumprecht, R. Kawamori, J. Shaban, et al. The IMPROVE study—a multinational, observational study in type 2 diabetes: baseline characteristics from eight national cohorts. Int J Clin Pract. 2008;62:1809-1819 x A. Philis-Tsimikas, G. Charpentier, P. Clauson, G.M. Ravn, V.L. Roberts, B. Thorsteinsson. Comparison of once-daily insulin detemir with NPH insulin added to a regimen of oral antidiabetic drugs in poorly controlled type 2 diabetes. Clin Ther. 2006;28:1569-1581 [Erratum in: Clin Ther 2006;28:1967] x A.J. Martorella. Iatrogenic hypoglycemia in patients with type 2 diabetes: comparison of insulin analog premixes and human insulin premixes. Postgrad Med. 2011;123:7-16 . Explanations for these findings might again be better self-management behaviours, including more consistent eating patterns as a result of patient education given at the time of starting insulin analogues, although the possibility that investigator recording of hypoglycaemia events differed in some way at 24 weeks from that at baseline cannot be excluded.

Unsurprisingly, differences in hypoglycaemia rate for the study insulin regimens were, however, influenced by pre-study therapy type. Thus, prior insulin users reported a marked decrease in incidence of events in all therapy subgroups, with the greatest numerical reductions being in those transferring to insulin detemir. Insulin-naïve patients generally experienced a slight increase in the rate of overall hypoglycaemia, with the exception of the insulin aspart group. This is not consistent with reports from RCTs. Regional baseline rates of hypoglycaemia varied considerably, but all reported reductions in overall hypoglycaemia (Table 4). The greatest reductions in rate were evident from north Africa and Russia, explained by the baseline rates being highest.

Even though the large body of data generated by this study offers the opportunity to explore other important disease and therapy-related questions, there were limitations inherent in the study design. In particular, concomitant medication and dietary intake were not controlled, and the latter remains largely unmeasurable. The study was non-randomised and lacked a standardised treatment protocol and a control arm, with most safety and efficacy parameters based on participant recall, diverse diaries or self-reported information. The circumstances under which participants came under the care of the investigators are not known, and these could have been a trigger for starting modern insulin therapy while at the same time improving other aspects of diabetes care. Additionally, the findings could have been influenced by a study effect as, although entry was retrospective, further data collection was prospective following informed consent. Against that view, insulin dose titration after baseline was small.

Another limitation of the study is the heterogeneity of global healthcare systems involved, although this was part of the design, with the intention of trying to identify how cultural, resource and perhaps genetic influences might have different effects on the safety and efficacy profile of the different analogues. This proved not to be the case because, for the most part, the patterns of improvement in glucose control (including postprandial), blood lipid control and hypoglycaemia, and without weight gain, were consistent between regions.

In summary, in people whose HbA1c suggested diabetes management neglect, starting an insulin analogue, whether in a current insulin user or not, appears to provide a valuable opportunity for broad improvements in self-management and metabolic control, independently of the type of insulin begun. With both lipids and blood pressure improving, cardiovascular risk will clearly be usefully reduced. Furthermore, starting these insulins was not associated in these circumstances with any tolerability or safety problem, notably of hypoglycaemia or body weight. Further analysis of this large database will seek to define the factors predicting changes in metabolic profile, and to build guidelines for diabetes management in the individual.

 
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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 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.

References

Label Authors Title Source Year
[6]

References in context

  • This result is not unexpected, similar findings with regard to pre-study treatment regimen having been reported in the IMPROVE observational study of 52,419 people from 11 countries with T2D starting or switching to biphasic insulin aspart as part of routine clinical care [6].
    Go to context

P. Valensi, M. Benroubi, V. Borzi, J. Gumprecht, R. Kawamori, J. Shaban, et al. The IMPROVE study—a multinational, observational study in type 2 diabetes: baseline characteristics from eight national cohorts Int J Clin Pract. 2008;62:1809-1819 2008
[26]

References in context

  • Body weight gain in 6 months with an HbA1c improvement of around 22mmol/mol (2.0%) or more would be expected to be around 4kg [26], due to amelioration of urinary glycosuria and glucose concentration-driven glucose metabolism [27]; that this did not occur would suggest that participants and advising healthcare teams took advantage of the starting of insulin analogues to enhance self-care behaviours.
    Go to context

H. Yki-Järvinen Combination therapies with insulin in type 2 diabetes Diabetes Care. 2001;24:758-767 2001
[27]

References in context

  • Body weight gain in 6 months with an HbA1c improvement of around 22mmol/mol (2.0%) or more would be expected to be around 4kg [26], due to amelioration of urinary glycosuria and glucose concentration-driven glucose metabolism [27]; that this did not occur would suggest that participants and advising healthcare teams took advantage of the starting of insulin analogues to enhance self-care behaviours.
    Go to context

B. Ravikumar, P.E. Carey, J.E. Snaar, D.K. Deelchand, D.B. Cook, R.D. Neely, et al. Real-time assessment of postprandial fat storage in liver and skeletal muscle in health and type 2 diabetes Am J Physiol Endocrinol Metab. 2005;288:E789-E797 2005
[28]

References in context

  • While improvements in glycaemic control are usually associated with an increased risk of hypoglycaemia [28], the global cohort from this study reported a decrease in the rate of all hypoglycaemic episodes from 3.1 events/person-year at baseline to 1.6 events/person-year in the 4 weeks before the end of the study.
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UK Prospective Diabetes Study (UKPDS) Group Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33) Lancet. 1998;352:837-853 1998

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