Therapy of Type 2 Diabetes Mellitus: UPDATE

Glycemic Goals in the Care of Patients with Type Glycemic Goals in the Care of Patients with Type 2 Diabetes- 2013 ADA and AACE Guidelines:2 Diabetes- 2013 ADA and AACE Guidelines:

Room For Improvement Room For Improvement

(Be HAPPY/ Avoid Burnout, While Caring for Patients with DM)(Be HAPPY/ Avoid Burnout, While Caring for Patients with DM)

Stan Schwartz MD, FACP, FACEAffiliate, Main Line Health System

Clinical Associate Professor of Medicine, Emeritus, U of Pa.

stschwar@gmail.comPart 2

Early Treatment Decreases Micro and Macro Vascular

RISK

Impact of Intensive Therapy in Type 2 Diabetes Summary of Major Clinical Trials:

BUT Subset Evaluations Show Reduced CV Outcomes if shorter duration of DM, without significant pre-existing complications

Study Microvascular Macrovascular Mortality

UGDP ↔ ↔ ↔UKPDS ↓ ↓ ↔ ↓ ↔ ↓

DCCT/EDIC* ↓ ↓ ↔ ↓ ↔ ↔ACCORD ↓ ↔ ↑(unadj.), ↔ (adj.)

ADVANCE ↓ ↔ ↔VADT ↔ ↔ ↔

Initial Trial Long Term Follow-up

Meinert CL. Diabetes. 1970;19(suppl):789-830.

Goldner MG. JAMA. 1971;218(9):1400-1410.UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998;352:854-865. Holman RR. N Engl J Med. 2008;359(15):1577-1589.DCCT Research Group. N Engl J Med. 1993;329;977-986.Nathan DM, et al. N Engl J Med. 2005;353:2643-2653.

Gerstein HC, et al. N Engl J Med. 2008;358:2545-2559.Patel A, et al. N Engl J Med. 2008;358:2560-2572.Duckworth W, et al. N Engl J Med. 2009;360.

*T1DM study.

↑↑- - likely due to likely due to hypoglycemia hypoglycemia and weight gainand weight gain

Intensive treatment/standard treatment

Weight ofstudy size

Odds ratio(95% CI)

Odds ratio(95% CI)

Participants Events

UKPDS 3071/1549 426/259 8.6% 0.75 (0.54–1.04)

PROactive* 2605/2633 164/202 20.2% 0.81 (0.65–1.00)

ADVANCE 5571/5569 310/337 36.5% 0.92 (0.78–1.07)

VADT 892/899 77/90 9.0% 0.85 (0.62–1.17)

ACCORD 5128/5123 205/248 25.7% 0.82 (0.68–0.99)

Overall 17267/15773 1182/1136 100% 0.85 (0.77–0.93)

0.4 0.6 0.8 1.0 1.2 1.4 1.6 1.8Intensive treatment better Standard treatment better

*Included on-fatal MI and death from all-cardiac mortality

Probability of events of CAD with intensive glucose-lowering vs. standard treatment

2.0

Intensive treatment/standard treatment

Weight ofstudy size

Odds ratio(95% CI)

Odds ratio(95% CI)

Participants Events

UKPDS 3071/1549 221/141 21.8% 0.78 (0.62–0.98)

PROactive* 2605/2633 119/144 18.0% 0.83 (0.64–1.06)

ADVANCE 5571/5569 153/156 21.9% 0.98 (0.78–1. 23)

VADT 892/899 64/78 9.4% 0.81 (0.58–1.15)

ACCORD 5128/5123 186/235 28.9% 0.78 (0.64–0.95)

Overall 17267/15773 743/754 100% 0.83 (0.75–0.93)

Intensive treatment better Standard treatment better

Probability of events of non-fatal MI with intensive glucose-lowering vs. standard treatment

www.thelancet.com. Vol 373 May 23, 2009.

Lancet Meta-analysis

0.4 0.6 0.8 1.0 1.2 1.4 1.61.8 2.0

0.9% Dec. HbA1c,17% Dec. non-fatal MI,

15% Dec. CV events of CAD

Hypoglycemia Outcomes VADT, ACCORD, ADVANCE

Consequences of Hypoglycemia• Prolonged QT- intervals- Diabetologia 52:42,2009

–Can be of pronged duration IJCP Sup 129, 7/02

–Greater with higher catecholamine levels Europace 10,860

• Associated with Angina Diabetes Care 26, 1485, 2003 / Ischemic EKG changes Porcellati, ADA2010

• Associated with Arrhythmias• Associated with Sudden Death Endocrine Practice 16,¾ 2010

• Increased Variabilty- explains highest mortality in intensive group had highest HgA1c in

ACCORD ( increases inflammation, ICU mortality Hirsch ADA2010)

RISK OF TOO TIGHT CONTROL OF HYPERGLYCEMIA IN HOSPITALS

VALUE OF CONTROLLING HYPERGLYCEMIA IN HOSPITAL

So given epidemiologic data, CV risk/glucose data and now ADVANCE, VADT, ACCORD, implications of weight gain and

hypogycemia, what are/ should be goals (SSS)1. ADA- stayed at <7.0 AACE – stayed at < 6.5

Lowest possible as long as no undue risk of hypoglycemia and visceral weight gain

2. ADA and AACE- a. Start early in DM -

implications for prevention- lifestyle and drug therapy of metabolic syndrome and IGT

b. do not aim for aggressive control in those with significant pre-existing CV disease

Disagree- lowest possible without hypoglycemia, weight gain3.Modify goals for ‘elderly’

Disagree- lowest possible without hypoglycemia, weight gain

Greater Survival in Elderly (>75yo) with lower HgA1c

EASD , 9/2010

So…WHY NOT BE AGGRESSIVE IN GLYCEMIC CONTROL

IF… NOT USING HYPOGLYCEMIC AGENTS