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#81 Type 2 Diabetes and A1c targets: Pragmatic dogma


CLINICAL QUESTION
QUESTION CLINIQUE
What are reasonable Hemoglobin A1c (A1c) targets for our patients with Type 2 Diabetes Mellitus?


BOTTOM LINE
RÉSULTAT FINAL
While many patients can safely attain an A1c at or just below 7%, older patients, those with long-standing diabetes, multiple co-morbidities, and/or high risk of hypoglycemia, reasonable targets are perhaps 7-8% or even higher.



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EVIDENCE
DONNÉES PROBANTES
Intense management of blood glucose in Type 2 Diabetes examined in ≥ ten meta-analyses. 1-10
  • Studies varied in ages, co-morbidities, medications, etc., making evidence interpretation and application more difficult.
Five reasonably sized trials fall into two groups:
  • Newly diagnosed diabetics, age ~50’s, few co-morbidities, receiving single glucose lowering therapy (to start) versus diet.
    • UKPDS 33: 3,867 patients, sulfonylurea or insulin (median ten year A1c 7.0% versus 7.9%).11
      • Over ten years, significant reduction in death Number Needed to Treat (NNT)=29 and myocardial infarction (MI) NNT=36. 12
    • UKPDS 34: 753 patients, metformin (median ten year A1c 7.4% versus 8.0%). 13
      • Over ten years, significant reduction in death NNT=14 and MI NNT=16. 12
  • Older, established diabetics, age ~60’s, more co-morbidities, receiving multiple glucose-lowering therapies (to start) for intense versus conventional.
    • ACCORD:14 10,251 patients, x3.5 years, AIC 6.4% versus 7.5%.
    • ADVANCE:15 11,140 patients, x5 years, A1C 6.5% versus 7.3%.
    • Veterans:16 1,791 patients, x5.6 years, A1C 6.9% versus 8.4%.
    • Intense management led to:
      • Microvascular improvement:17 Prevented visual deterioration (three lines worse on Snellen chart) NNT=60 and loss of light touch sensation NNT=49.
      • No benefit in cardiovascular outcomes14-16 except one study found reduced non-fatal MI NNT=100. 15
      • Inconsistently worse: mortality in one study14 Number Needed to Harm (NNH)=96 and hospitalization in another15 NNH=48.
      • Consistently worse:14-16 Weight gain (gain ≥10kg14 NNH=8), and hypoglycemia (severe requiring medical assistance NNH=15).
Context:
  • New US-European Guidelines18 recommend less stringent targets in patients with longer disease duration, shorter life expectancy, increased co-morbidities, and high risk of hypoglycemia or other adverse events.
  • Cohort data indicates that in established diabetics, A1c of 7.5% may have the lowest mortality.19
  • Macrovascular complications such as cardiovascular events are much more common than end-stage microvascular endpoints such as progression to dialysis or blindness.11,20


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Author(s)
Auteur(s)
  • G. Michael Allan MD CCFP
  • Jacques Romney MD FRCPC

1. Tkác I. Diabetes Res Clin Pract. 2009; 86 Suppl 1:S57-62.

2. Marso SP, Kennedy KF, House JA, et al. Diab Vasc Dis Res. 2010; 7:119-30.

3. Ray KK, Seshasai SR, Wijesuriya S, et al. Lancet. 2009; 373:1765-72.

4. Hemmingsen B, Lund SS, Gluud C, et al. BMJ. 2011; 343:d6898.

5. Boussageon R, Bejan-Angoulvant T, Saadatian-Elahi M, et al. BMJ. 2011; 343:d4169.

6. Zhang CY, Sun AJ, Zhang SN, et al. Ann Med. 2010; 42:305-15.

7. Macisaac RJ, Jerums G. Heart Lung Circ. 2011; 20:647-54.

8. Kelly TN, Bazzano LA, Fonseca VA, et al. Ann Intern Med. 2009; 151:394-403.

9. Mannucci E, Monami M, Lamanna C, et al. Nutr Metab Cardiovasc Dis. 2009; 19:604- 12.

10. Turnbull FM, Abraira C, Anderson RJ, et al. Diabetologia. 2009; 52:2288-98.

11. UK Prospective Diabetes Study (UKPDS) Group. Lancet 1998; 352:837–53.

12. Holman RR, Paul SK, Bethel MA, et al. N Engl J Med. 2008; 359:1577-89.

13. UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998; 352:854–65.

14. Action to Control Cardiovascular Risk in Diabetes Study Group (ACCORD). N Engl J Med. 2008; 358:2545-59.

15. ADVANCE Collaborative Group. N Engl J Med. 2008; 358:2560-72.

16. Duckworth W, Abraira C, Moritz T, et al. N Engl J Med. 2009; 360:129-39.

17. Smail-Beigi F, Craven T, Banerji MA, et al. Lancet. 2010; 376:419-30.

18. Inzucchi SE, Bergenstal RM, Buse JB, et al. Diabetes Care. 2012; 35:1364-79.

19. Currie CJ, Peters JR, Tynan A, et al. Lancet. 2010; 375:481-9.

20. Bruno G, Biggeri A, Merletti F, et al. Diabetes Care. 2003; 26:2353-8.

Authors do not have any conflicts of interest to declare.

Les auteurs n’ont aucun conflit d’intérêts à déclarer.

Most recent review: 05/08/2016

By: Ricky D. Turgeon BSc(Pharm) ACPR PharmD

Comments:

Evidence Updated: No new evidence; Bottom Line: No change.

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