1. LecturePad Master Slide

2. Agents Available for Controlling Hyperglycemia
Class
A1C Reduction %
Fasting vs PPG
Hypoglycemia
Weight Change
Dosing (times/day)
Outcome Studies
Metformin
1.5 F No
Neutral 2
UKPDS
Insulin (Long Acting)
Yes
Gain 1
DIGAMI
(DCCT)
Insulin (Rapid Acting)
PPG
1-4
Sulfonylureas
TZDs
PROactive
RECORD
GLP-1 Agonists
Loss
None

3. LDL-P and LDL-C Discordance Multi-Ethnic Study of Atherosclerosis (MESA)
The clinical significance of LDL-P discordance in the setting of low LDL-C is shown in this graph. When LDL-C is low, CVD risk is a function of LDL-P. When LDL-P is low, CVD event rates are low. When LDL-P is not low, despite low LDL-C, CVD events are substantially higher.
Otvos JD et al. J Clin Lipidol Mar-Apr 5(2):

4. Collaborative Treatment Approach Empower Patient for Self-Care
Interventions that empower patients help them make informed, self-directed decisions and manage their diabetes in a way that works for their lives.
Assessment of
self-management
beliefs, behavior, and
knowledge
Individually tailored
strategies and
problem solving
Collaborative
goal setting
Personal
Action
Plan
Identification of
personal barriers
and supports
Funnell MM. Eur J Endocrinol Oct;151 Suppl2:T19-22.
Denver, EA et al. Diabetes Care Aug;26(8):

5. Work Together to Prioritize Treatment Goals and Establish Good Self-Care
Agree on an agenda by using communication strategies that avoid overwhelming newly diagnosed patients with “too much, too soon”
Exchange Information
Multiple
Behaviors
Explore
Importance
Establish
Rapport
Set
Agenda
Single
Behavior
Assess Importance
and Confidence
Readiness
Build
Confidence
Reduce Resistance
Rollnick S, Mason P, and Butler C. Health behavior change: a guide for practitioners. Edinburgh, Scotland: Churchill Livingstone, 2000. 5

6. Byetta (Exenatide)

7. Exenatide QW Reduced Systolic Blood Pressure (SBP)
Δ SBP (mm/Hg)
Exenatide QW
Metformin
Insulin Glargine
Exenatide BID
Sitagliptin
Liraglutide
Pioglitazone

8. Exenatide QW Reduced Diastolic Blood Pressure (DBP)
Δ DBP (mm/Hg)
Exenatide QW
Metformin
Insulin Glargine
Exenatide BID
Sitagliptin
Liraglutide
Pioglitazone

9. DURATION 1: Exenatide QW Resulted in Similar A1C Improvements Across Background Therapies
D/E MET Only MET+ SU MET All SU All TZD All N
BsLn % % % % % %
Δ A1c (%)
-1.6%
-1.9%
-1.9%
-1.9%
-1.9%
-2.0%

10. DURATION 1: Fasting Lipids Improved at 2 Years on Exenatide QW

11. DURATION 2: Exenatide QW Demonstrated Superior A1CReduction vs Sitagliptin and Pioglitazone

12. DURATION 2: Exenatide QW Demonstrated Superior Weight Reduction vs Sitagliptin and Pioglitazone
Δ Body Weight (kg)
Time (weeks)
Exenatide QW
Sitagliptin
Pioglitazone

13. Fasting Lipids

14. DURATION 2: Exenatide QW Improved CV Risk Markers
Δ BNP (%) (pg/mL)
Δ ACR (%) (mg/g)
Δ hsCRP (%) (mg/L)

15. Markers of CV Risk

16. EXSCEL: Pragmatic CV Outcomes Trial
EXenatide Study of Cardiovascular Event Lowering
Pragmatic, placebo-controlled, double-blinded trial evaluating CV outcomes in patients with type 2 diabetes
Hypothesis: EQW, when used as part of usual care, lowers the risk for major macrovascular events compared to usual care alone
Globe trial: 9,500 patients, ~4.5 years median exposure
Run jointly by Duke Clinical Research Institute and University of Oxford Diabetes Trial Unit
Clinicaltrials.gov ID:NCT

17. Summary Once-weekly exenatide elicited superior improvements in:
Glucose control
Body weight reduction
All treatments were associated with:
Low rates of hypoglycemia
Low rates of withdrawal due to GI AEs
Exenatide QW was the ONLY treatment that improved SBP
All treatments improved HDL, hsCRP, and adiponectin
Exenatide QW: Improved BNP and albumin/creatinine
Pioglitazone: Improved HDL (greatest), triglycerides and PAI-1 – but was associated with increased total cholesterol and BNP

18. AACE 2012 Guidelines Glucose Testing and Interpretation
Result
Diagnosis
Fasting Plasma Glucose (mg/dL)
≤ 99
Normal
Impaired Fasting Glucose
≥126
Diabetes (confirmed on repeat testing)
Glucose, mg/dL (oral glucose tolerance test, 2 hrs after ingestion of 75 g glucose load)
≤ 139
Impaired Glucose Tolerance
≥ 200
Hemoglobin A1c (%) (screening test)
≤ 5.4
High Risk/Prediabetes (requires screening by glucose criteria)
≥ 6.5
AACE Diabetes Care Plan Guidelines, Endocr Pract. 2011;17 (Suppl 2)

19. Comprehensive Diabetes Care Treatment Goals
AACE 2012 Guidelines Comprehensive Diabetes Care Treatment Goals Glucose
Comprehensive Diabetes Care Treatment Goals
Parameter
Treatment Goal
Reference
Hemoglobin A1c (%)
Individualize on the basis of age, comorbidities, duration of disease. In general, ≤ 6.5 for most. Closer to normal for healthy and less stringent for less healthy.
Statement by an American Association of Clinical Endocrinologists / American College of Endocrinology consensus panel on type 2 diabetes mellitus: An algorithm for glycemic control Endocr Pract. 2009;15:
Fasting Plasma Glucose (mg/dL)
< 110
2-Hour Postprandial Glucose (mg/dL)
< 140
Inpatient Hyperglycemia, Glucose (mg/dL)
American Association of Clinical Endocrinologists; American Diabetes Association. American Association of Clinical Endocrinologists and American Diabetes Association consensus statement on inpatient glycemic control. Endocr Pract. 2009;15:
AACE Diabetes Care Plan Guidelines, Endocr Pract. 2011;17 (Suppl 2)

20. Comprehensive Diabetes Care Treatment Goals
AACE 2012 Guidelines Comprehensive Diabetes Care Treatment Goals Lipids
Comprehensive Diabetes Care Treatment Goals
Parameter
Treatment Goal
Reference
LDL-C (mg/dL)
≤ 70 highest risk; <100 high risk
Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation. 2004;110:
Non-HDL-C (mg/dL)
<100 highest risk; <130 high risk
Apo B (mg/dL)
<80 highest risk; <90 high risk
HDL-C (mg/dL)
>40 Men; >50 Women
Triglycerides (mg/dL)
<150
Highest Risk: DM and CVD; High Risk: DM without CVD
AACE Diabetes Care Plan Guidelines, Endocr Pract. 2011;17 (Suppl 2)

21. AACE 2012 Guidelines Comprehensive Diabetes Care Treatment Goals Other
Parameter
Treatment Goal
Reference
Systolic Blood Pressure (mm Hg)
<130
National Heart, Lung, and Blood Institute Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure; National High Blood Pressure Education Program Coordinating Committee. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: The JNC 7 report. JAMA. 2003;289:
Diastolic Blood Pressure (mm Hg)
<80
Weight Loss
Reduce weight by at least 5-10%. Avoid weight gain.
Statement by an American Association of Clinical Endocrinologists / American College of Endocrinology consensus panel on type 2 diabetes mellitus: An algorithm for glycemic control Endocr Pract. 2009;15:
Aspirin Therapy
For secondary CVD prevention or primary prevention for patients at very high risk (DM without CVD)
Younis et al. Expert Opin Pharmacother. 2010;11: ATT Collaboration, Lancet. 2009;373: Zhang et al. Diabetes Res Clin Pract. 2010;87: Ong et al. Diabetes Care. 2010;33:
AACE Diabetes Care Plan Guidelines, Endocr Pract. 2011;17 (Suppl 2)

22. ADA / EASD 2012 Position Statement Key Points
Glycemic targets and glucose-lowering therapies must be individualized.
Diet, exercise, and education remain the foundation of any type 2 diabetes treatment program.
Unless there are prevalent contraindications, metformin is the optimal first-line drug.
After metformin, there are limited data to guide us. Combination therapy with an additional 1–2 oral or injectable agents is reasonable, aiming to minimize side effects where possible.
Ultimately, many patients will require insulin therapy alone or in combination with other agents to maintain glucose control.
All treatment decisions, where possible, should be made in conjunction with the patient, focusing on his/her preferences, needs, and values.
Comprehensive cardiovascular risk reduction must be a major focus of therapy.
Management of Hyperglycemia in Type 2 Diabetes: A Patient-Centered Approach.
Diabetes Care Apr 19.

23. ADA / EASD 2012 Position Statement Initial Drug Monotherapy
Healthy Eating, Weight Control, Increased Physical Activity
Metformin
Decrease HbA1c
High
Hypoglycemia Risk
Low
Weight
Neutral/Loss
Side Effects
GI/Lactic Acidosis
Cost
If needed to reach individualized HbA1c target after ~3 months, proceed to two-drug combination
Management of Hyperglycemia in Type 2 Diabetes: A Patient-Centered Approach.
Diabetes Care Apr 19.

24. ADA / EASD 2012 Position Statement Two Drug Combination Therapy
Metformin
AND SU
TZDs
DPP-4 I
GLP-1 RA
Insulin
Decrease HbA1c
High
Intermediate
Highest
Hypoglycemia Risk
Moderate
Low
Weight
Gain
Neutral
Loss
Side Effects
Hypoglycemia
Edema, HF, Fx’s
Rare GI
Cost
Variable
If needed to reach individualized HbA1c target after ~3 months, proceed to three-drug combination
Management of Hyperglycemia in Type 2 Diabetes: A Patient-Centered Approach.
Diabetes Care Apr 19.

25. ADA / EASD 2012 Position Statement Three Drug Combination Therapy
Metformin
AND SU
TZDs
DPP-4 I
GLP-1 RA
Insulin
TZD
OR DPP-4 I
OR DDP-4 I
OR TZD
OR GLP-1 RA
OR Insulin
If combination therapy that includes insulin has failed to achieve HbA1c target after 3-6 months, proceed to more complex insulin strategy, usually in combination with one or two non-insulin agents.
(Multiple Daily Doses)
Management of Hyperglycemia in Type 2 Diabetes: A Patient-Centered Approach.
Diabetes Care Apr 19.