Targets for Glycemic Control

Targets for Glycemic Control

Y L N 2018 Clinical Practice Guidelines O E S U L A Targets for Glycemic Control N O S R E P Chapter 8 S. Ali Imran MBBS FRCP (Edin) FRCPC, Gina Agarwal MBBS PhD MRCGP CCFP FCFP, Harpreet S. Bajaj MD MPH ECNU FACE, Stuart Ross MB ChB FRACP FRCPC Disclaimer All Content contained on this slide deck is the property of Diabetes Canada, its content suppliers or its licensors as the case may be, and is protected by Canadian and international copyright, trademark, and other applicable laws. Diabetes Canada grants personal, limited, revocable, non-transferable and non-exclusive license to access and read content in this slide deck for personal, non-commercial and not-for-profit use only. The slide deck is made available for lawful, personal use only and not for commercial use.

S R PE S U L A ON Y L N O E The unauthorized reproduction, distribution of this copyrighted work is not permitted. For permission to use this slide deck for commercial or any use other than personal, please contact [email protected] 2018 Diabetes Canada CPG Chapter 8. Targets for Glycemic Control 2018 Key Changes Addition of target category of Functionally dependent 7.1%-8.0% Y L N EO Lower FPG and PPG targetsSin individuals not

U L meeting an A1C targetA of <7.0% N O S R the recommendation for Strengthening Eof P targeting an A1C 6.5% in people with type 2 diabetes to further lower the risk of chronic kidney disease and retinopathy if they are at low risk of hypoglycemia based on class of antihyperglycemic agent(s) taken and patient characteristics A1C, glycated hemoglobin; FPG, fasting plasma glucose; PPG, postprandial glucose PERSONAL USE ONLY 2018 Diabetes Canada CPG Chapter 8. Targets for Glycemic Control Targets Checklist A1C 7.0% for MOST people with Y L diabetes N O E S U

L A1C 6.5% for SOME A people with type N O 2 diabetes RS PE A1C 7.1%-8.5% in people with specific features PERSONAL USE ONLY 2018 Diabetes Canada CPG Chapter 8. Targets for Glycemic Control A1C Targets 6. 5 7. 0 7.1 8.5 2018 Adults with type 2 diabetes to reduce the risk of CKD and retinopathy if at low risk of hypoglycemia Y TYPE 2 MOST ADULTS WITH TYPE 1LOR DIABETES ON E

Sdependent* 7.1-8.0%: Functionally U L 7.1-8.5%: A N hypoglycemia and/or Recurrent severe O S unawareness hypoglycemia R Limited PE life expectancy Frail elderly and/or with dementia** Avoid higher A1C to minimize risk of symptomatic hyperglycemia and acute and chronic complications A1C measurement not recommended. Avoid symptomatic End of life hyperglycemia and any hypoglycemia * Based on class of antihyperglycemic medication(s) utilized and persons characteristics ** see Diabetes in Older People chapter CKD; chronic kidney disease PERSONAL USE ONLY 2018 Diabetes Canada CPG Chapter 8. Targets for Glycemic Control To achieve A1C 7.0% A1C (%) For most patients Y

L N O E S4.0-7.0 U L A ON 7.0 If A1C 7.0% not ERS achieved despiteP the above PG targets Preprandial PG (mmol/L) 4.0-5.5 2 hour Postprandial PG (mmol/L) 5.0-10.0 5.0-8.0 PG, plasma glucose PERSONAL USE ONLY 2018 Diabetes Canada CPG Chapter 8. Targets for Glycemic Control Correlation between A1C and

estimated mean glucose values A1C values (%) 5.56.5 6.56.9 7.57.9 Y L N EO 7.07.4 8.08.5 S U L 8.69.3 9.410.1 10.210.9 Estimated 6.27.7 7.88.5 A N mean glucose O S R (mmol/L) PE A1C, glycated hemoglobin PERSONAL USE ONLY 2018 Diabetes Canada CPG Chapter 8. Targets for Glycemic Control

Y L N O < 7.0% E S U L A N O S R E P PERSONAL USE ONLY DCCT N = 1441 T1DM Intensive ( 3 injections/day or CSII) S R PE S U L A ON

Y L N O E vs. Conventional (1-2 injections per day) PERSONAL USE ONLY 2018 Diabetes Canada CPG Chapter 8. Targets for Glycemic Control DCCT: Reduction in Retinopathy Primary Prevention Secondary Intervention 54% LYRRR 76% RRR (95% CI 62-85%) S R PE S U L A ON

N O E (95% CI 3966%) RRR = relative risk reduction CI = confidence interval The Diabetes Control and Complications Trial Research Group. N Engl J Med 1993;329:977-986. PERSONAL USE ONLY 2018 Diabetes Canada CPG Chapter 8. Targets for Glycemic Control DCCT: Reduction in Albuminuria Primary Prevention 34% RRR (p<0.04) PE RS S U L A ON Secondary Intervention Y L N

O E 43% RRR (p=0.001) 56% RRR (p=0.01) RRR = relative risk Solid line = risk of developing microalbuminuria reduction Dashed line = risk of developing macroalbuminuria CI = confidence interval The Diabetes Control and Complications Trial Research Group. N Engl J Med 1993;329:977-986. PERSONAL USE ONLY 2018 Diabetes Canada CPG Chapter 8. Targets for Glycemic Control DCCT: Reduction in Neuropathy S R PE S U L A ON Y L N

O E The Diabetes Control and Complications Trial Research Group. N Engl J Med 1993;329:977-986. PERSONAL USE ONLY 2018 Diabetes Canada CPG Chapter 8. Targets for Glycemic Control DCCT/EDIC: Early intensive glucose control leads to long-term reduction nonfatal MI, stroke or CVD death MI, stroke or CV death 0.12 0.10 Y L N O 57% risk reduction E S (P=0.02; 95% U CI: 12 L A79%) N O S R E P 0.08

0.06 0.04 0.02 Conventiona l treatment Intensive treatmen t 0.00 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 Years since entry DCCT/EDIC Study Research Group. N Engl J Med 2005;353:26432653. 19

20 21 PERSONAL USE ONLY DCCT/EDIC: Early intensive glucose control leads to long-term reduction in mortality 2018 Diabetes Canada CPG Chapter 8. Targets for Glycemic Control HR 0.67 S U L A ON (95% CI, 0.46-0.99) P=0.045 S R PE Y L N O E DCCT/EDIC Research Group. JAMA 2015;313:45-53. PERSONAL USE ONLY

A1C (%) UKPDS 33: Intensive glucose control with sulfonylureas or insulin in type 2 diabetes N = 3867 Recent Onset T2DM Y L N 9 O ConventionalSE U 7.9%L A N O 8 S R E P Intensive 7.0% 7 6 0 0 3 UKPDS Study Group. Lancet 1998:352:837-53.

6 9 12 15 PERSONAL USE ONLY 2018 Diabetes Canada CPG Chapter 8. Targets for Glycemic Control UKPDS: Legacy Effect of Early Intensive Glucose Control 2007: After total of 20 years follow-up Aggregate Endpoint 1997 2007 Y L N Any diabetes related endpoint RRR: 12% 9% O E P: 0.029 0.040 S U L A Microvascular disease N O S R E P

RRR: P: 25% 24% 0.0099 0.001 Myocardial infarction RRR: P: 16% 15% 0.052 0.014 All-cause mortality RRR: P: 6% 0.44 13% 0.007 Holman R, et al. N Engl J Med 2008;359. PERSONAL USE ONLY 2018 Diabetes Canada CPG Chapter 8. Targets for Glycemic Control Y L N

O < 6.5% E S U L A N O S R E P PERSONAL USE ONLY S U L A ON Y L N O E S R PE ADVANCE N = 11,140 T2DM Intensive (A1C 6.5% with gliclazide MR) vs. Standard glycemic control PERSONAL USE ONLY

2018 Diabetes Canada CPG Chapter 8. Targets for Glycemic Control ADVANCE: Glucose Control 10.0 Y L N Standard O E 9.0 8.0 Mean A1C (%) 7.0 S R PE 6.0 S control 7.3% U L A ON 5.0 0.0

0 6 p< 0.001 Intensive control 6.5% 12 18 24 30 36 42 48 54 60 66 Follow-up (months) ADVANCE Collaborative Group. N Engl J Med 2008;358:24. PERSONAL USE ONLY 2018 Diabetes Canada CPG Chapter 8. Targets for Glycemic Control ADVANCE: Treatment Effect on the Primary Microvascular Outcomes New/worsening nephropathy, retinopathy 25 20 Cumulative incidence (%) 15 10

5 P0 E 0 RS 6 Y L HR 0.86 (0.77- N Standard 0.97) E O control S p = 0.01 U L A ON Intensive control 12 18 24 30 36 42 48 54 60 66 Follow-up (months) 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. PERSONAL USE ONLY 2018 Diabetes Canada CPG Chapter 8. Targets for Glycemic Control RS

BENEFIT PE S U L A ON Y L N O E HYPOGLYCEMIA PERSONAL USE ONLY 2018 Diabetes Canada CPG Chapter 8. Targets for Glycemic Control Y L N O 7.1 8.5% E S U L A N O S R E

P PERSONAL USE ONLY S R PE S U L A ON Moorhouse P, Rockwood K. J R Coll Physicians Edinb 2012;42:333-340. Y L N O E PERSONAL USE ONLY 2018 Diabetes Canada CPG Chapter 8. Targets for Glycemic Control Recommendations 1-3 1. Glycemic targets should be individualized [Grade D, Consensus] 2. In most people with type 1 or type Y 2 diabetes, an L Nto reduce the risk A1C 7.0% should be targeted O

E 1A] and, if of microvascular [Grade A, Level S U L implemented early inAthe course of disease, CV complications [Grade ONB, Level 3] 3. S R In people with PE type 2 diabetes, an A1C 6.5% may be targeted to reduce the risk of CKD [Grade A, Level 1A] and retinopathy [Grade A, Level 1A], if they are assessed to be at low risk of hypoglycemia based on class of antihyperglycemic medication(s) utilized and the persons characteristics [Grade D, Consensus] CKD, chronic kidney disease; CV, cardiovascular PERSONAL USE ONLY 2018 Diabetes Canada CPG Chapter 8. Targets for Glycemic Control 2018 Recommendation 4 4. A higher A1C target may be considered in people with diabetes with the goals of avoiding Y hypoglycemia and over-treatment L related

to N antihyperglycemic therapy, with any of the O following: [Grade D, Consensus]USE L 7.1-8.0% Functionally dependent: A Nsevere hypoglycemia, O History of recurrent S R especially if E accompanied by hypoglycemia P unawareness: 7.1-8.5% Limited life expectancy: 7.1-8.5% Frail elderly and/or with dementia: 7.1-8.5% End of life: A1C measurement not recommended. Avoid symptomatic hyperglycemia and any hypoglycemia PERSONAL USE ONLY 2018 Diabetes Canada CPG Chapter 8. Targets for Glycemic Control Recommendation 5

2018 5. In order to achieve an A1C 7.0%, people with diabetes should aim for: Fasting plasma glucose (FPG) orLY preprandial PG N target of 4.07.0 mmol/L and aO2h PPG target of E S 5.010.0 mmol/L [Grade B,ULevel 2 for type 1; Grade B, Level 2 L A N O If an A1C target 7.0% cannot be achieved with a S R FPG target ofE4.0-7.0 mmol/L and PPG target of 5.0 P for type 2 diabetes] 10.0 mmol/L, further FPG lowering to 4.0 to 5.5 mmol/L and/or PPG lowering to 5.08.0 mmol/L may be considered, but must be balanced against the risk of hypoglycemia [Grade D, Level 4 for FPG target for type 2 diabetes; Grade D, Consensus for FPG target for type 1 diabetes; Grade D, Level 4 for PPG target for type 2 diabetes; Grade D, Consensus for PPG target for type 1 diabetes]

PERSONAL USE ONLY 2018 Diabetes Canada CPG Chapter 8. Targets for Glycemic Control Key Messages Optimal glycemic control is fundamental to the management of diabetes Y L N plasma Both fasting and postprandial O glucose levels correlate U with SE the risk of L complications and contribute to the measured A N A1C value O S R Glycemic targets should be individualized PE based on the individuals age, duration of diabetes, risk of severe hypoglycemia, presence or absence of hypoglycemia unawareness, frailty or functional dependence and life expectancy PERSONAL USE ONLY

2018 Diabetes Canada CPG Chapter 8. Targets for Glycemic Control Key Messages for People with Diabetes Try to keep your blood glucose as close to your Y to delay or target range as possible. This willLhelp ON prevent complications of diabetes E S U Lglucose and A1C can vary Target ranges for blood A N O and depend on a Spersons age, medical R E conditions and other risk factors. Work with your P diabetes healthcare team to determine what your target A1C, and blood glucose target range (fasting and after meals) should be PERSONAL USE ONLY Visit guidelines.diabetes.ca S

R PE S U L A ON Y L N O E PERSONAL USE ONLY Or download the App S R PE S U L A ON Y L N O E PERSONAL USE ONLY

Diabetes Canada Clinical Practice Guidelines Y L http://guidelines.diab N O etes.ca E health-care S for U L A providers R E P N O S 1-800-BANTING (2268464) http://diabetes.ca for people with diabetes PERSONAL USE ONLY

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