canadian diabetes association 2013 clinical practice guidelines targets for glycemic control chapter...

Canadian Diabetes Association 2013 Clinical Practice Guidelines

Targets for Glycemic Control

Chapter 8

S. Ali Imran, Rémi Rabasa-Lhoret, Stuart Ross

guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.caCopyright © 2013 Canadian Diabetes Association

Targets Checklist

A1C ≤7.0% for MOST people with diabetes

A1C ≤6.5% for SOME people with T2DM

A1C 7.1-8.5% in people with specific features

2013


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?


DCCTN = 1441 T1DM

Intensive(≥ 3 injections/day or CSII)

vs. \

Conventional (1-2 injections per day)


Reduction in Retinopathy

The Diabetes Control and Complications Trial Research Group. N Engl J Med 1993;329:977-986.

Primary Prevention Secondary 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 microalbuminuriaDashed line = risk of developing macroalbuminuria

DCCT: Reduction in Albuminuria


34% RRR (p<0.04)

43% RRR(p=0.001)

56% RRR(p=0.01)

Primary Prevention Secondary Intervention


RRR = relative risk reductionCI = confidence interval


Reduction in Neuropathy



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,

stro

ke

or

CV

de

ath

Conventionaltreatment

Intensivetreatment

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21

Years since entry

0.12

0.10

0.08

0.06

0.04

0.02

0.00


UKPDS: N = 3867 T2DM

06

8

9

0 3 6 9 12 15

A1C

(%

)

Conventional7.9%

Intensive7.0%7

UKPDS Study Group. Lancet 1998:352:837-53.


Holman RR et al. N Engl J Med 2008;359.


After median 8.5 years post-trial follow-up

Aggregate Endpoint 1997 2007

Any diabetes related endpoint RRR: 12% 9% P: 0.029 0.040

Microvascular disease RRR: 25% 24% P: 0.0099 0.001

Myocardial infarction RRR: 16% 15% P: 0.052 0.014

All-cause mortality RRR: 6% 13% P: 0.44 0.007

Legacy Effect of Earlier Glucose Control

Holman R, et al. N Engl J Med 2008;359.


To achieve A1C ≤7.0%

A1C (%) Preprandial PG (mmol/L)

2-h postprandial PG (mmol/L)

For most patients

≤7.0 4.0-7.0 5.0-10.0(5-8 if A1C not at

target)

2013


ADVANCEN = 11,140 T2DM

Intensive (A1C ≤6.5% with gliclazide MR)

vs.

Standard glycemic control


ADVANCE: Glucose Control

Follow-up (months)

Mean A1C (%)

Standard control 7.3%

Intensive control 6.5%

10.0

9.0

8.0

7.0

6.0

5.0

0.00 6 12 18 24 30 36 42 48 54 60 66

p < 0.001

ADVANCE Collaborative Group. N Engl J Med 2008;358:24.


ADVANCE: Treatment Effect on the Primary Microvascular Outcomes

• New/worsening nephropathy, retinopathy

66

Cumulative incidence (%)

Follow-up (months)

HR 0.86 (0.77-0.97)p = 0.01 Standard

control

Intensive control

25

20

15

10

5

00 6 12 18 24 30 36 42 48 54 60

Intensive Standard HR p

Nephropathy/retinopathy (%) 9.4 10.9 0.86 0.01

Nephropathy (%) 4.1 5.2 0.79 0.006

Retinopathy (%) 6.0 6.3 0.95 NS

ADVANCE Collaborative Group. N Engl J Med 2008;358:24.


BENEFITHYPO-

GLYCEMIA

7.1 - 8.5%


Consider A1C 7.1-8.5% if …

• Limited life expectancy• High level of functional dependency

2013


Consider A1C 7.1-8.5% 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


Consider A1C 7.1-8.5% 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


Individualizing A1C Targets

which must be balanced against the risk of hypoglycemia

Consider 7.1-8.5% if:

2013


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].


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].


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


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


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 4.0-7.0 mmol/L and a 2-hr

postprandial PG target of 5.0-10.0 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 5.0-8.0 mmol/L should be

achieved [Grade D, Consensus, for type 1 diabetes; Grade D, Level 4 for

type 2 diabetes].


CDA Clinical Practice Guidelines

http://guidelines.diabetes.ca – for professionals

1-800-BANTING (226-8464)

http://diabetes.ca – for patients

http://guidelines.diabetes.ca/

http://diabetes.ca/

canadian diabetes association 2013 clinical practice guidelines targets for glycemic control chapter...

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