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Journal of Endocrinological Investigation

, Volume 37, Issue 5, pp 477–495 | Cite as

Achieving HbA1c targets in clinical trials and in the real world: a systematic review and meta-analysis

  • Edoardo Mannucci
  • Matteo Monami
  • Ilaria Dicembrini
  • Attilio Piselli
  • Massimo Porta
Original Article

Abstract

Purpose

To review the proportion of diabetic patients reaching recommended therapeutic goals, as reported in intervention trials and observational studies, and to analyse the factors associated with success or failure in achieving these targets.

Methods

A systematic review and meta-analysis through a Medline and Embase search for “diabetes” and “HbA1c” has been performed between 1 January 1995 and 1 March 2012 on randomised clinical trials and observational studies on type 1 (T1DM) or type 2 diabetes (T2DM) enrolling at least 200 patient*year.

Results

Out of 169 patient groups in RCTs with results available for analysis, the overall proportion of patients reaching HbA1c ≤7 % was 36.6 (34.1–39.1) %. Of these, 8 groups included T1DM subjects [proportion at target (PAT) 27.2 (22.7–32.3) %] and 161 T2DM patients [PAT 37.1 (34.5–39.7) %]. In patients with T2DM on oral agents, at multivariate analysis, higher success rate was associated with higher age and body mass index (BMI), lower duration of diabetes, lower proportion of Caucasians and more recent publication year. Among the insulin treated, only duration of diabetes retained a significant association with success rate. Among 41 groups from cross-sectional studies, 6 and 22 were composed of patients with T1DM and T2DM, respectively, and the remaining 13 included both types. Patients at target for HbA1c were 19.8 (12.4–30.1), 36.1 (31.5–41.0), and 39.0 (32.9–45.3) %, respectively. Higher age, lower BMI, shorter duration of diabetes and a higher proportion of males and Caucasians were associated with a higher success rate.

Conclusions

Available data show that a wide distance remains between recommended targets and actual achievements in routine clinical practice.

Keywords

HbA1c targets Systematic review and meta-analysis Diabetes 

Notes

Conflict of interest

Authors declare no conflicts of interest that might bias their work.

Supplementary material

40618_2014_69_MOESM1_ESM.doc (66 kb)
Supplementary material 1 (DOC 66 kb)

References

  1. 1.
    Haffner SM, Lehto S, Rönnemaa T, Pyörälä K, Laakso M (1998) Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med 339(4):229–234PubMedCrossRefGoogle Scholar
  2. 2.
    Beckman JA, Creager MA, Libby P (2002) Diabetes and atherosclerosis: epidemiology, pathophysiology, and management. JAMA 287(19):2570–2581PubMedCrossRefGoogle Scholar
  3. 3.
    The Diabetes Control and Complications Trial Research Group (1993) The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 329:977–986CrossRefGoogle Scholar
  4. 4.
    UK Prospective Diabetes Study (UKPDS) Group (1998) 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 352:837–853CrossRefGoogle Scholar
  5. 5.
    ADVANCE Collaborative Group, Patel A, MacMahon S, Chalmers J et al (2008) Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med 358(24):2560–2572PubMedCrossRefGoogle Scholar
  6. 6.
    Mannucci E, Monami M, Lamanna C, Gori F, Marchionni N (2009) Prevention of cardiovascular disease through glycemic control in type 2 diabetes: a meta-analysis of randomized clinical trials. Nutr Metab Cardiovasc Dis 19(9):604–612PubMedCrossRefGoogle Scholar
  7. 7.
    Boussageon R, Bejan-Angoulvant T, Saadatian-Elahi M et al (2011) Effect of intensive glucose lowering treatment on all cause mortality, cardiovascular death, and microvascular events in type 2 diabetes: meta-analysis of randomised controlled trials. BMJ 343:d4169PubMedCentralPubMedCrossRefGoogle Scholar
  8. 8.
    Inzucchi SE, Bergenstal RM, Buse JB, American Diabetes Association (ADA), European Association for the Study of Diabetes (EASD) et al (2012) Management of hyperglycemia in type 2 diabetes: a patient-centered approach: position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 35(6):1364–1379PubMedCentralPubMedCrossRefGoogle Scholar
  9. 9.
    American Association of Clinical Endocrinologist (2007) Medical guidelines for clinical practice for the management of diabetes mellitus. http://www.aace.com
  10. 10.
    IDF Clinical Guidelines Task Force (2006) Global Guideline for Type 2 Diabetes: recommendations for standard, comprehensive, and minimal care. Diabet Med 23(6):579–593CrossRefGoogle Scholar
  11. 11.
    Moher D, Liberati A, Tetzlaff J, Altman DG (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med 151:264–269PubMedCrossRefGoogle Scholar
  12. 12.
    Jadad AR, Moore RA, Carroll D et al (1996) Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trial 17(1):1–12CrossRefGoogle Scholar
  13. 13.
    Begg CB, Mazumdar M (1994) Operating characteristics of a rank correlation test for publication bias. Biometrics 50:1088–1101PubMedCrossRefGoogle Scholar
  14. 14.
    Egger M, Davey SG, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315:629–634PubMedCentralPubMedCrossRefGoogle Scholar
  15. 15.
    Eeg-Olofsson K, Cederholm J, Nilsson PM, Gudbjörnsdóttir S, Eliasson B, Steering Committee of the Swedish National Diabetes Register (2007) Glycemic and risk factor control in type 1 diabetes: results from 13,612 patients in a national diabetes register. Diabetes Care 30(3):496–502PubMedCrossRefGoogle Scholar
  16. 16.
    Eliasson B, Cederholm J, Nilsson P, Gudbjörnsdóttir S (2005) The gap between guidelines and reality: type 2 diabetes in a National Diabetes Register 1996–2003. Diabet Med 22:1420–1426PubMedCrossRefGoogle Scholar
  17. 17.
    Bruno G, Merletti F, Bargero G et al (2008) Changes over time in the prevalence and quality of care of type 2 diabetes in Italy: the Casale Monferrato surveys, 1988 and 2000. Nutr Metab Cardiovasc Dis 18:39–45PubMedCrossRefGoogle Scholar
  18. 18.
    Saydah SH, Fradkin J, Cowie CC (2004) Poor control of risk factors for vascular disease among adults with previously diagnosed diabetes. JAMA 291:335–342PubMedCrossRefGoogle Scholar
  19. 19.
    Ford ES, Li C, Little RR, Mokdad AH (2008) Trends in A1C concentrations among US adults with diagnosed diabetes from 1999 to 2004. Diabetes Care 31:102–104PubMedCrossRefGoogle Scholar
  20. 20.
    Hovind P, Tarnow L, Rossing K et al (2003) Decreasing incidence of severe diabetic microangiopathy in type 1 diabetes. Diabetes Care 26:1258–1264PubMedCrossRefGoogle Scholar
  21. 21.
    Klein R, Knudtson MD, Lee KE, Gangnon R, Klein BEK (2008) The Wisconsin Epidemiologic Study of Diabetic Retinopathy XXII. The twenty-five-year progression of retinopathy in persons with type 1 diabetes. Ophthalmology 115:1859–1868PubMedCentralPubMedCrossRefGoogle Scholar
  22. 22.
    Antonetti DA, Klein R, Gardner TW (2012) Diabetic retinopathy. NEJM 366:1227–1239PubMedCrossRefGoogle Scholar
  23. 23.
    Sharma SK, Joshi SR, Kumar A, Unnikrishnan AG, Hoskote SS, Moharana AK, Chakkarwar PN, Vaz JA, PRESENT Study Group (2008) Efficacy, safety and acceptability of biphasic insulin aspart 30 in Indian patients with type 2 diabetes: results from the PRESENT study. J Assoc Physicians India 56:859–863PubMedGoogle Scholar
  24. 24.
    Sharma SK, Al-Mustafa M, Oh SJ, Azar ST, Shestakova M, Guler S, Vaz JA (2008) 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 24(3):645–652PubMedCrossRefGoogle Scholar
  25. 25.
    Hanberger L, Samuelsson U, Lindblad B, Ludvigsson J, Swedish Childhood Diabetes Registry SWEDIABKIDS (2008) A1C in children and adolescents with diabetes in relation to certain clinical parameters: the Swedish Childhood Diabetes Registry SWEDIABKIDS. Diabetes Care 31(5):927–929 (Epub 2008 Jan 30)PubMedCrossRefGoogle Scholar
  26. 26.
    Pan CY, Ho LT, Soegondo S, Prodjosudjadi W, Suwanwalaikorn S, Lim SC, Chan TM, Chow KW, Thoenes M, Choi DS, DEMAND Study Investigators (2008) Prevalence of albuminuria and cardiovascular risk profile in a referred cohort of patients with type 2 diabetes: an Asian perspective. Diabetes Technol Ther 10(5):397–403PubMedCrossRefGoogle Scholar
  27. 27.
    Pan C, Yang W, Barona JP, Wang Y, Niggli M, Mohideen P, Wang Y, Foley JE (2008) Comparison of vildagliptin and acarbose monotherapy in patients with type 2 diabetes: a 24-week, double-blind, randomized trial. Diabet Med 25(4):435–441 Epub 2008 Mar 13PubMedCrossRefGoogle Scholar
  28. 28.
    Cheung NW, Conn JJ, d’Emden MC, Gunton JE, Jenkins AJ, Ross GP, Sinha AK, Andrikopoulos S, Colagiuri S, Twigg SM, Australian Diabetes Society (2009) Position statement of the Australian Diabetes Society: individualisation of glycated haemoglobin targets for adults with diabetes mellitus. Med J Aust 191(6):339–344PubMedGoogle Scholar
  29. 29.
    Plöckinger U, Topuz M, Langer M, Reuter T (2010) Problems of diabetes management in the immigrant population in Germany. Diabetes Res Clin Pract 87(1):77–86PubMedCrossRefGoogle Scholar
  30. 30.
    Kaplan SH, Billimek J, Sorkin DH, Ngo-Metzger Q, Greenfield S (2010) Who can respond to treatment? Identifying patient characteristics related to heterogeneity of treatment effects. Med Care 48(6 Suppl):16 (Diabetes Res Clin Pract. 2006; 73(2):198–204)Google Scholar
  31. 31.
    Tong PC, Ko GT, So WY, Chiang SC, Yang X, Kong AP, Ozaki R, Ma RC, Cockram CS, Chow CC, Chan JC (2008) Use of anti-diabetic drugs and glycaemic control in type 2 diabetes—The Hong Kong Diabetes Registry. Diabetes Res Clin Pract 82(3):346–352PubMedCrossRefGoogle Scholar
  32. 32.
    Elis A, Rosenmann L, Chodick G, Heymann AD, Kokia E, Shalev V (2008) The association between glycemic, lipids and blood pressure control among Israeli diabetic patients. QJM 101(4):275–280PubMedCrossRefGoogle Scholar
  33. 33.
    Erasmus RT, Blanco Blanco E, Okesina AB, Gqweta Z, Matsha T (1999) Assessment of glycaemic control in stable type 2 black South African diabetics attending a peri-urban clinic. Postgrad Med J 75(888):603–606PubMedCentralPubMedGoogle Scholar
  34. 34.
    Wexler DJ, Grant RW, Meigs JB, Nathan DM, Cagliero E (2005) Sex disparities in treatment of cardiac risk factors in patients with type 2 diabetes. Diabetes Care 28(3):514–520PubMedCrossRefGoogle Scholar
  35. 35.
    Saydah SH, Fradkin J, Cowie CC (2004) Poor control of risk factors for vascular disease among adults with previously diagnosed diabetes. JAMA 291(3):335–342PubMedCrossRefGoogle Scholar
  36. 36.
    McAlister FA, Majumdar SR, Eurich DT, Johnson JA (2007) The effect of specialist care within the first year on subsequent outcomes in 24,232 adults with new-onset diabetes mellitus: population-based cohort study. Qual Saf Health Care 16(1):6–11PubMedCentralPubMedCrossRefGoogle Scholar
  37. 37.
    Muggeo M, Verlato G, Bonora E et al (1995) The Verona Diabetes Study: a population-based survey on known diabetes mellitus prevalence and 5-year all-cause mortality. Diabetologia 38:318PubMedCrossRefGoogle Scholar
  38. 38.
    Trento M, Gamba S, Gentile L, ROMEO Investigators et al (2010) Rethink Organization to iMprove Education and Outcomes (ROMEO): a multicenter randomized trial of lifestyle intervention by group care to manage type 2 diabetes. Diabetes Care 33(4):745–747PubMedCentralPubMedCrossRefGoogle Scholar
  39. 39.
    Gill G (2003) Intensified treatment of type 2 diabetes—positive effects on blood pressure, but not glycaemic control. QJM 96:833–836PubMedCrossRefGoogle Scholar
  40. 40.
    Gerstein HC, Miller ME, Byington RP et al (2008) Effects of intensive glucose lowering in type 2 diabetes. NEJM 358:2545–2559PubMedCrossRefGoogle Scholar
  41. 41.
    Gaede P, Vedel P, Larsen N et al (2003) Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes. NEJM 348:383–393PubMedCrossRefGoogle Scholar
  42. 42.
    Haugstvedt A, Wentzel-Larsen T, Graue M, Søvik O, Rokne B (2010) Fear of hypoglycaemia in mothers and fathers of children with Type 1 diabetes is associated with poor glycaemic control and parental emotional distress: a population-based study. Diabet Med 27(1):72–78PubMedCrossRefGoogle Scholar
  43. 43.
    Drew LM, Berg C, King P et al (2011) Depleted parental psychological resources as mediators of the association of income with adherence and metabolic control. J Fam Psychol 25(5):751–758PubMedCrossRefGoogle Scholar
  44. 44.
    Reach G, Michault A, Bihan H et al (2011) Patients’ impatience is an independent determinant of poor diabetes control. Diabetes Metab 37:497–504PubMedCrossRefGoogle Scholar
  45. 45.
    Reach G (2011) Obedience and motivation as mechanisms for adherence to medication: a study in obese type 2 diabetic patients. Patient Prefer Adherence 5:523–531PubMedCentralPubMedCrossRefGoogle Scholar
  46. 46.
    Hirsch IB, Brownlee M (2010) Beyond haemoglobin A1c—need for additional markers of risk for diabetic microvascular complications. JAMA 303:2291–2292PubMedCrossRefGoogle Scholar
  47. 47.
    Hemmingsen B, Lund SS, Gluud C et al (2011) Intensive glycaemic control for patients with type 2 diabetes: systematic review with meta-analysis and trial sequential analysis of randomised clinical trials. BMJ 343:d6898PubMedCentralPubMedCrossRefGoogle Scholar
  48. 48.
    Standards of Medical Care in Diabetes (2012) Diabetes Care 35:S11–S63Google Scholar

Copyright information

© Italian Society of Endocrinology (SIE) 2014

Authors and Affiliations

  • Edoardo Mannucci
    • 1
  • Matteo Monami
    • 2
  • Ilaria Dicembrini
    • 1
  • Attilio Piselli
    • 3
  • Massimo Porta
    • 3
  1. 1.Diabetes AgencyCareggi Teaching HospitalFlorenceItaly
  2. 2.Section of Geriatric Cardiology and Medicine, Department of Cardiovascular MedicineUniversity of Florence and Careggi Teaching HospitalFlorenceItaly
  3. 3.Department of Medical SciencesUniversity of TurinTurinItaly

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