An observational non-interventional study of people with diabetes beginning or changed to insulin analogue therapy in non-Western countries: The A1chieve study
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
The progressive nature of type 2 diabetes (T2D) over time results in the majority of people with diabetes being unable to maintain HbA1c targets on a management regimen of lifestyle changes with oral glucose-lowering drugs (OGLDs)  and  x R.C. Turner, C.A. Cull, V. Frighi, R.R. Holman, UK Prospective Diabetes Study (UKPDS) Group. Glycaemic control with diet, sulfonylurea, metformin, or insulin in patients with type 2 diabetes mellitus: progressive requirement for multiple therapies (UKPDS 49). JAMA. 1999;281:2005-2012 x A. Wright, A.C. Felix Burden, R.B. Paisey, C.A. Cull, R.R. Holman, for the UK Prospective Diabetes Study Group. Sulfonylurea inadequacy. Efficacy of addition of insulin over 6 years in patients with type 2 diabetes in the UK Prospective Diabetes Study (UKPDS 57). Diabetes Care. 2002;25:330-336 . Furthermore, suboptimal glycaemic control commonly persists even in insulin users  x S. Gough, K.B. Frandsen, A.D. Toft. Failure of insulin monotherapy in patients with type 2 diabetes: a population-based study. Diabetes. 2006;55(Suppl. 1):A114 . What is sometimes described as “clinical inertia” or “patient resistance” further results in people remaining on inappropriate therapy regimens for too long , , and  x M. Davies. The reality of glycaemic control in insulin treated diabetes: defining the clinical challenges. Int J Obes Relat Metab Disord. 2004;28(Suppl. 2):S14-S22 x H.J. Lüddeke, S. Sreenan, S. Aczel, S. Maxeiner, M. Yenigun, P. Kozlovski, et al. PREDICTIVE – a global, prospective observational study to evaluate insulin detemir treatment in types 1 and 2 diabetes: baseline characteristics and predictors of hypoglycaemia from the European cohort. Diabetes Obes Metab. 2007;9:428-434 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 . It is known that when therapies are actively assessed, titrated and increased in number, glycaemic targets are more likely to be achieved  x A.J. Garber, J. Wahlen, T. Wahl, P. Bressler, R. Braceras, E. Allen, et al. Attainment of glycaemic goals in type 2 diabetes with once-, twice-, or thrice-daily dosing with biphasic insulin aspart 70/30 (the 1-2-3 study). Diabetes Obes Metab. 2006;8:58-66 . Accordingly, the American Diabetes Association (ADA) and International Diabetes Federation (IDF) guidelines emphasise the importance of continually modifying therapy regimens when HbA1c goals are no longer maintained. In practice, however, most people with T2D still experience significant periods when their HbA1c levels are well above 53–64 mmol/mol (7.0–8.0%), increasing their risk of developing diabetes-related health complications , , and  x S.H. Saydah, J. Fradkin, C.C. Cowie. Poor control of risk factors for vascular disease among adults with previously diagnosed diabetes. JAMA. 2004;291:335-342 x J.B. Saaddine, B. Cadwell, E.W. Gregg, M.M. Engelgau, F. Vinicor, G. Imperatore, et al. Improvements in diabetes processes of care and intermediate outcomes: United States, 1988–2002. Ann Intern Med. 2006;144:465-474 x I.M. Stratton, A.I. Adler, H.A. Neil, D.R. Matthews, S.E. Manley, C.A. Cull, et al. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ. 2000;321:405-412 .
Modern insulin analogues were designed to aid achievement of better glycaemic control while addressing concerns over tolerability, notably in regard of hypoglycaemia and body weight gain  and  x M. Peyrot, R.R. Rubin, T. Lauritzen, S.E. Skovlund, F.J. Snoek, D.R. Matthews, et al. International DAWN Advisory Panel. Resistance to insulin therapy among patients and providers: results of the cross-national Diabetes Attitudes, Wishes, and Needs (DAWN) study. Diabetes Care. 2005;28:2673-2679 x M. Korytkowski. When oral agents fail: practical barriers to starting insulin. Int J Obes Relat Metab Disord. 2002;26(Suppl. 3):S18-S24 , and their clinical benefits have been assessed in randomised controlled trials (RCTs) and observational studies , , , , , , , and  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 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 S.K. Sharma, M. Al-Mustafa, S.J. Oh, S.T. Azar, M. Shestakova, S. Guler, J.A. Vaz. Biphasic insulin aspart 30 treatment in patients with type 2 diabetes poorly controlled on prior diabetes treatment: results from the PRESENT study. Curr Med Res Opin. 2008;24:645-652 x A. Dornhorst, H.J. Lüddeke, C. Koenen, M. Meriläinen, A. King, A. Robinson, et al. Transferring to insulin detemir from NPH insulin or insulin glargine in type 2 diabetes patients on basal-only therapy with oral antidiabetic drugs improves glycaemic control and reduces weight gain and risk of hypoglycaemia: 14-week follow-up data from PREDICTIVE. Diabetes Obes Metab. 2008;10:75-81 . These studies have shown that a change of therapy from OGLDs or conventional insulin preparations to insulin analogues can be associated with clinically significant improvements in efficacy measures, while being well tolerated.
Well-designed RCTs are a rigorous way of assessing treatments in a restricted population sample. However, they focus on a selected patient group under intensive clinical supervision, and may not represent the reality of the people in everyday life, or when seen in normal clinical practice. Furthermore, these studies are often performed in restricted geographical areas, such that information from less well-resourced countries is relatively sparse. While there are limitations with observational studies with regard to potential bias, study effects and lack of a control group, they can have less stringent inclusion and exclusion criteria, and, being much less costly, can address larger numbers of people in more diverse environments , , and  x H.M. Krumholz. Outcomes research: generating evidence for best practice and policies. Circulation. 2008;118:309-318 x S. MacMahon, R. Collins. Reliable assessment of the effects of treatment on mortality and major morbidity. II: observational studies. Lancet. 2001;357:455-462 x W. Yang, A. Zilov, P. Soewondo, O.M. Bech, F. Sekkal, P.D. Home. Observational studies: going beyond the boundaries of randomized clinical trials. Diabetes Res Clin Pract. 2010;88S:S3-S9 .
The aim of the A1chieve study was, therefore, to broaden the knowledge of the clinical safety and effectiveness of insulin analogues in a large and diverse population from a globally broad variety of clinical care. As the largest observational study ever conducted in insulin therapy, A1chieve has explored both beginning insulin in non-insulin users and switching to these analogues in more than 65,000 people from 28 different countries across four continents. Part of the intention behind the study was to explore how the insulins performed in countries in which resource, practice and genetic differences might be expected (or not) to influence outcomes.
|S. Gough, K.B. Frandsen, A.D. Toft||Failure of insulin monotherapy in patients with type 2 diabetes: a population-based study||Diabetes. 2006;55(Suppl. 1):A114||2006|
|A.J. Garber, J. Wahlen, T. Wahl, P. Bressler, R. Braceras, E. Allen, et al.||Attainment of glycaemic goals in type 2 diabetes with once-, twice-, or thrice-daily dosing with biphasic insulin aspart 70/30 (the 1-2-3 study)||Diabetes Obes Metab. 2006;8:58-66||2006|
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