Canadian Diabetes Association 2013 Clinical Practice Guidelines Targets for Glycemic Control Chapter 8 S. Ali Imran, Rémi Rabasa-Lhoret, Stuart Ross

guidelines.diabetes.ca | BANTING ( ) | diabetes.ca Copyright © 2013 Canadian Diabetes Association Targets Checklist A1C ≤7.0% for MOST people with diabetes A1C ≤6.5% for SOME people with T2DM A1C % in people with specific features 2013

guidelines.diabetes.ca | BANTING ( ) | diabetes.ca Copyright © 2013 Canadian Diabetes Association Questions to Address What should the A1C be for most people & why? Who should we be more aggressive with & why? Who should we be less aggressive with & why?

guidelines.diabetes.ca | BANTING ( ) | diabetes.ca Copyright © 2013 Canadian Diabetes Association DCCT N = 1441 T1DM Intensive (≥ 3 injections/day or CSII) vs. \ Conventional (1-2 injections per day)

guidelines.diabetes.ca | BANTING ( ) | diabetes.ca Copyright © 2013 Canadian Diabetes Association Reduction in Retinopathy The Diabetes Control and Complications Trial Research Group. N Engl J Med 1993;329: Primary PreventionSecondary Intervention 76% RRR (95% CI 62-85%) 54% RRR (95% CI 39-66%) RRR = relative risk reduction CI = confidence interval

Solid line = risk of developing microalbuminuria Dashed line = risk of developing macroalbuminuria DCCT: Reduction in Albuminuria The Diabetes Control and Complications Trial Research Group. N Engl J Med 1993;329: % RRR (p<0.04) 43% RRR (p=0.001) 56% RRR (p=0.01) Primary PreventionSecondary Intervention guidelines.diabetes.ca | BANTING ( ) | diabetes.ca Copyright © 2013 Canadian Diabetes Association RRR = relative risk reduction CI = confidence interval

guidelines.diabetes.ca | BANTING ( ) | diabetes.ca Copyright © 2013 Canadian Diabetes Association Reduction in Neuropathy The Diabetes Control and Complications Trial Research Group. N Engl J Med 1993;329:

guidelines.diabetes.ca | BANTING ( ) | diabetes.ca Copyright © 2013 Canadian Diabetes Association DCCT/EDIC Study Research Group. N Engl J Med 2005;353:2643–2653. DCCT/EDIC: Early intensive therapy reduced the risk of nonfatal MI, stroke or death from CVD 57% risk reduction (P=0.02; 95% CI: 12–79%) MI, stroke or CV death Conventional treatment Intensive treatment Years since entry

guidelines.diabetes.ca | BANTING ( ) | diabetes.ca Copyright © 2013 Canadian Diabetes Association UKPDS: N = 3867 T2DM A1C (%) Conventional 7.9% Intensive 7.0% 7 UKPDS Study Group. Lancet 1998:352:

guidelines.diabetes.ca | BANTING ( ) | diabetes.ca Copyright © 2013 Canadian Diabetes Association Holman RR et al. N Engl J Med 2008;359.

guidelines.diabetes.ca | BANTING ( ) | diabetes.ca Copyright © 2013 Canadian Diabetes Association After median 8.5 years post-trial follow-up Aggregate Endpoint Any diabetes related endpoint RRR: 12%9% P: Microvascular disease RRR: 25%24% P: Myocardial infarction RRR: 16%15% P: All-cause mortality RRR: 6%13% P: Legacy Effect of Earlier Glucose Control Holman R, et al. N Engl J Med 2008;359.

guidelines.diabetes.ca | BANTING ( ) | diabetes.ca Copyright © 2013 Canadian Diabetes Association To achieve A1C ≤7.0% 2013

guidelines.diabetes.ca | BANTING ( ) | diabetes.ca Copyright © 2013 Canadian Diabetes Association ADVANCE N = 11,140 T2DM Intensive (A1C ≤6.5% with gliclazide MR) vs. Standard glycemic control

guidelines.diabetes.ca | BANTING ( ) | diabetes.ca Copyright © 2013 Canadian Diabetes Association ADVANCE: Glucose Control Follow-up (months) Mean A1C (%) Standard control 7.3% Intensive control 6.5% p < ADVANCE Collaborative Group. N Engl J Med 2008;358:24.

guidelines.diabetes.ca | BANTING ( ) | diabetes.ca Copyright © 2013 Canadian Diabetes Association ADVANCE: Treatment Effect on the Primary Microvascular Outcomes New/worsening nephropathy, retinopathy 66 Cumulative incidence (%) Follow-up (months) HR 0.86 ( ) p = 0.01 Standard control Intensive control ADVANCE Collaborative Group. N Engl J Med 2008;358:24.

guidelines.diabetes.ca | BANTING ( ) | diabetes.ca Copyright © 2013 Canadian Diabetes Association BENEFIT HYPO- GLYCEMIA

guidelines.diabetes.ca | BANTING ( ) | diabetes.ca Copyright © 2013 Canadian Diabetes Association Consider A1C % if … Limited life expectancy High level of functional dependency 2013

guidelines.diabetes.ca | BANTING ( ) | diabetes.ca Copyright © 2013 Canadian Diabetes Association Moorhouse P, Rockwood K. J R Coll Physicians Edinb 2012;42:

guidelines.diabetes.ca | BANTING ( ) | diabetes.ca Copyright © 2013 Canadian Diabetes Association Consider A1C % if … Limited life expectancy High level of functional dependency Extensive coronary artery disease at high risk of ischemic events Multiple co-morbidities History of recurrent severe hypoglycemia Hypoglycemia unawareness Longstanding diabetes for whom is it difficult to achieve an A1C ≤ 7%, despite effective doses of multiple antihyperglycemic agents, including intensified basal-bolus insulin therapy 2013

guidelines.diabetes.ca | BANTING ( ) | diabetes.ca Copyright © 2013 Canadian Diabetes Association Consider A1C % if … Limited life expectancy High level of functional dependency Extensive coronary artery disease at high risk of ischemic events Multiple co-morbidities History of recurrent severe hypoglycemia Hypoglycemia unawareness Longstanding diabetes for whom is it difficult to achieve an A1C ≤ 7%, despite effective doses of multiple antihyperglycemic agents, including intensified basal-bolus insulin therapy 2013

guidelines.diabetes.ca | BANTING ( ) | diabetes.ca Copyright © 2013 Canadian Diabetes Association Individualizing A1C Targets which must be balanced against the risk of hypoglycemia Consider % if: 2013

guidelines.diabetes.ca | BANTING ( ) | diabetes.ca Copyright © 2013 Canadian Diabetes Association Recommendation 1 1.Glycemic targets should be individualized based on age, duration of diabetes, risk of severe hypoglycemia, presence or absence of cardiovascular disease, and life expectancy [Grade D, Consensus].

guidelines.diabetes.ca | BANTING ( ) | diabetes.ca Copyright © 2013 Canadian Diabetes Association Recommendation 2 and 3 2.Therapy in most individuals with type 1 or type 2 diabetes should be targeted to achieve an A1C ≤ 7.0% in order to reduce the risk of microvascular [Grade A, Level 1A] and, if implemented early in the course of disease, macrovascular complications [Grade B, Level 3] 3.An A1C ≤6.5% may be targeted in some patients with type 2 diabetes to further lower the risk of nephropathy [Grade A, Level 1] and retinopathy [Grade A, Level 1], but this must be balanced against the risk of hypoglycemia [Grade A, Level 1].

guidelines.diabetes.ca | BANTING ( ) | diabetes.ca Copyright © 2013 Canadian Diabetes Association Recommendation 4 4.Less stringent A1C targets (7.1 to 8.5% in most cases) may be appropriate in patients with type 1 or type 2 diabetes with any of the following [Grade D, Consensus]: – Limited life expectancy – High level of functional dependency – Extensive coronary artery disease at high risk of ischemic events – Insulin therapy 2013

guidelines.diabetes.ca | BANTING ( ) | diabetes.ca Copyright © 2013 Canadian Diabetes Association Recommendation 4 (continued) 4.(Continued) Less stringent A1C targets (7.1 to 8.5% in most cases) may be appropriate in patients with type 1 or type 2 diabetes with any of the following [Grade D, Consensus] : – Multiple co-morbidities – History of recurrent severe hypoglycemia – Hypoglycemia unawareness – Longstanding diabetes for whom it is difficult to achieve an A1C ≤7.0%, despite effective doses of multiple antihyperglycemic agents, including intensified basal-bolus insulin therapy 2013

guidelines.diabetes.ca | BANTING ( ) | diabetes.ca Copyright © 2013 Canadian Diabetes Association Recommendation 5 5.In order to achieve an A1C of ≤7.0%, people with diabetes should aim for: – A FPG or preprandial PG target of mmol/L and a 2-hr postprandial PG target of mmol/L [Grade B, Level 2, for type 1 diabetes; Grade B, Level 2, for type 2 diabetes]. – If an A1C target of <7.0% cannot be achieved with a postprandial PG target of 5.0 to 10.0 mmol/L, further postprandial BG lowering to mmol/L should be achieved [Grade D, Consensus, for type 1 diabetes; Grade D, Level 4 for type 2 diabetes].

guidelines.diabetes.ca | BANTING ( ) | diabetes.ca Copyright © 2013 Canadian Diabetes Association CDA Clinical Practice Guidelines – for professionals BANTING ( ) – for patients