1. CME Evaluation with Post-activity Survey
Prior to the start of the program, please check your syllabus to ensure you have the following printed program materials:
Baseline Survey
Located at the front of your syllabus
CME Evaluation with Post-activity Survey
Located at the back of your syllabus

3. Disclosures
The relevant financial relationships reported by faculty that they or their spouse/partner have with commercial interests are located on page 5 of your syllabus
The relevant financial relationships reported by the steering committee that they or their spouse/partner have with commercial interests are provided on page 5 of your syllabus
The relevant financial relationships reported by the non-faculty content contributors and/or reviewers that they or their spouse/partner have with commercial interests are located on page 5 of your syllabus

4. Off-label Discussion Disclosure
This educational activity may contain discussion of published and/or investigational uses of agents that are not indicated by the Food and Drug Administration. PCME does not recommend the use of any agent outside of the labeled indications. Please refer to the official prescribing information for each product for discussion of approved indications, contraindications and warnings. The opinions expressed are those of the presenters and are not to be construed as those of the publisher or grantors.
CAROL

5. Educational Objectives
At the conclusion of this activity, participants should be able to demonstrate the ability to:
Describe the relationships between glycemia and diabetes complications
Consider the HbA1C-lowering properties of GLP-1 agonists with their impacts on T2DM pathophysiology, CV risk factors, and hypoglycemic risk when individualizing treatment strategies for diabetic patients to reach target goals
Develop strategies to attain glycemic control throughout the life cycle of T2DM
Promote a collaborative approach to T2DM management, empowering the patient through individualized patient education to address and break down barriers for optimal outcomes, including adherence and injection-related barriers

6. Polling Question Baseline Survey
Please take out the Baseline Survey from your packet
Fill out the demographic information at the top of the form; as polling questions are asked throughout the program, please take a moment to select your answer to the corresponding question on this form
Your answers are important and will help us shape and improve future CME activities

7. Polling Question Baseline Survey
Please rate your confidence in managing T2DM in patients with prevalent macro- and/or microvascular comorbidities:
Expert
Very confident
Confident
Somewhat confident
Not confident

8. Polling Question Baseline Survey
Please rate your confidence in using GLP-1 receptor agonists to reduce HbA1C in your T2DM patients:
Expert
Very confident
Confident
Somewhat confident
Not confident

9. Polling Question Baseline Survey
How often do you incorporate a shared decision-making (SDM) approach to T2DM management?
Always
Frequently
Sometimes
Never
I do not know the definition of SDM

10. Polling Question Baseline Survey
A 42-year-old overweight man with a positive family history for MI presents with T2DM (A1C 8.5%). He also has uncontrolled hypertension and elevated cholesterol. He is being treated for his hypertension and cholesterol and receives metformin 1000 mg bid and glipizide 10 mg qd for his T2DM. He is tired of “taking so many pills.”
What do you consider?
Identify A1C target ~8% based on cardiovascular risk
Consider adding third oral agent
Recommend optimizing lifestyle interventions and re-evaluate therapy in 6 months if necessary
Consider adding or switching to injectable therapy, such as basal insulin and/or GLP-1 agonist

11. Polling Question Baseline Survey
A 42-year-old obese woman is receiving metformin, glimepiride, and sitagliptin. Her A1C is 8.1%. You recommend initiating a GLP-1 agonist, but the patient is afraid of needles.
What action do you take?
Avoid use of injectable agents in this patient
Tell the patient that taking shots is inevitable based on her history of type 2 diabetes
Tell the patient that she needs injectable therapy because her lifestyle interventions are insufficient
Show the patient needles used for GLP-1 injection and explain the difference between intramuscular and subcutaneous injections

12. Case 1: Introduction
Marcus is a 33-year-old overweight man with 4-year history of T2DM
Current medications: metformin 1000mg BID, glipizide 10mg QD
He has gained 15 lbs in 11 months; current BMI: 28.3 kg/m2
Lab evaluation
HbA1C: 8.2%
BP: 172/85 mm Hg
Total cholesterol: 242 mg/dL
Patient concerns
Robert reveals that he has not been adherent to his T2DM medications because he was “tired of taking so many pills every day”
He has experienced episodes of shakiness and extreme hunger before lunch and dinner
He is now worried about his health because his father recently suffered a fatal MI at age 57

13. I. Burden of T2DM and Its Complications

14. Polling Question Baseline Survey
Follow-up from the UKPDS study demonstrated that each 1% reduction in A1C was significantly associated with all of the following, EXCEPT:
Reduced risk for myocardial infarction
Reduced risk for death due to diabetes
Reduced risk for microvascular complications
Reduced risk for microvascular complications, but not macrovascular outcomes

15. Statistics shown are for all ages
Diabetes Prevalence in the US, 2012 National Diabetes Statistics Report, 2014
Statistics shown are for all ages
CDC. National Diabetes Statistics Report: Estimates of Diabetes and Its Burden in the United States. Atlanta, GA: US Department of Health and Human Services, 2014.

16. Pathophysiologic Progression of T2DM and Its Vascular Complications
Relative function
Time (years)
β-cell failure
Insulin secretion
Insulin resistance 50
100
150
200
250
–10 –5 5 10 15 20 25 30
IFG
IGT
OBESITY
Glucose (mg/dL)
Fasting glucose
Postprandial glucose
DM diagnosis
300
350
MICROVASCULAR COMPLICATIONS
MACROVASCULAR COMPLICATIONS
UNCONTROLLED HYPERGLYCEMIA
T2DM
IFG = impaired fasting glucose
IGT = impaired glucose tolerance
T2DM = type 2 diabetes mellitus
Adapted from Ramlo-Halsted BA et al. Clin Diabetes. 2000;18:80-84.

17. Relationship of HbA1C to Risk of Microvascular Complications
Relative Risk
Retinopathy
Nephropathy
Neuropathy
Microalbumin 15 13 11 9 7 5 3 1 6 8 10 12
HbA1C (%)
Used with permission from Skyler JS. Endocrinol Metab Clin North Am. 1996;25:

18. 14%-16% reduction in cardiovascular events per 1% A1C reduction
UKPDS: Macrovascular Complications Increase as Glycemic Control Worsens
Fatal and nonfatal MI
Heart failure 10 10
P<0.0001
P=0.021
Hazard ratio
Hazard ratio 1 1
14% decrease per 1%
reduction in A1C
16% decrease per 1%
reduction in A1C
0.5
0.5 5 6 7 8 9 10 5 6 7 8 9 10
Updated mean A1C
concentration (%)
Updated mean A1C
concentration (%)
14%-16% reduction in cardiovascular events per 1% A1C reduction
Stratton IM et al. BMJ. 2000:321; 18

19. UKPDS Study-End and 10-year Follow-Up Results
2007
10-year post-trial follow-up
(non-interventional)
UKPDS original results:
intensive vs conventional treatment
1977–1991
Randomization
1997
9%*
12%*
15%*
16%
Any diabetes-related endpoint
Myocardial infarction
Microvascular disease
In type 2 diabetes, improvements in glycemic control reduce the risk of complications
24%*
25%*
*P<0.05; intensive vs conventional treatment
Adapted from Holman et al. N Engl J Med. 2008;359:
UKPDS Study Group. Lancet. 1998;352:

20. Implications of ACCORD, ADVANCE, and VADT for Microvascular Risk
Microvascular disease:
Lowering A1C to ≤7.0% reduces microvascular and neuropathic complications in type 2 diabetes
If achievable without causing significant hypoglycemia or other adverse events, even lower A1C goals may be suggested for selected individuals having:
Short duration of diabetes
Long life expectancy
No significant CVD
Inzucchi SE et al. Diabetes Care. 2012;35:
Garber AJ et al. Endocr Pract. 2013;19:1-48. 20 20

21. Implications of ACCORD, ADVANCE, and VADT for Macrovascular Risk
Macrovascular disease:
Controversies regarding the impact of intensive glycemic control that exceeds an A1C goal of <7.0% on CVD outcomes compared to standard glycemic control
Lowering A1C to a goal of ≤7.0% is a reasonable glycemic goal until more evidence becomes available
Long-term follow-up of the DCCT and UKPDS cohorts suggests that treating to an A1C goal below or near 7.0% yields long-term reductions in the risk of macrovascular disease, if instituted in the years soon after diagnosis of diabetes
Inzucchi SE et al. Diabetes Care. 2012;35:
Garber AJ et al. Endocr Pract. 2013;19:1-48. 21 21

22. Obesity and T2D: A Common Burden
County-level Estimates of Diagnosed T2D Among US Adults, 2011
Obesity Prevalence Among US Adults, 2013
Obesity = BMI ≥30 kg/m2 or ~30 lbs. overweight for 5’4” person
CDC Behavioral Risk Factor Surveillance Systems; CDC Diabetes Public Health Resource Center.

23. II. How Well Are We Controlling T2DM?

24. Progress in Achieving A1C Goals: 2007-2012
National Committee for Quality Assurance, 2013.

25. Lessons from the DCCT and UKPDS Sustained Intensification of Therapy is Difficult
9.0
8.1
7.3
7.9 4 6 8 10
HbA1C (%)
6.5
+ 4
+ 6 yrs
DCCT
EDIC
DCCT EDIC
(Type 1) 7 2
10 yrs
UKPDS (Type 2), Insulin Group
Normal
Baseline
DCCT/EDIC Research Group. N Engl J Med. 2000;342:
Steffes et al. Diabetes (suppl. 2) 50:A63.
UK Prospective Diabetes Study Group (UKPDS) 33. Lancet. 1998;352:

26. Adherence to Prescribed Drugs in Patients with Type 2 Diabetes
Drug class n
% Adherent
95% CI
Oral antidiabetic drugs 66
50.0
Antihypertensive drugs 62
Lipid-lowering drugs 33
69.7
Antiplatelet drugs 40
77.5
All drugs 82
35.4
Mateo JF et al. Int J Clin Pract. 2006;60:

27. Clinical Inertia Failure to Advance Therapy When Required
Percentage of Subjects advancing when HbA1C >8%
100
At Insulin Initiation, the average patient had:
5 years with HbA1C >8%
10 years with HbA1C >7% 80
66.6% 60
% Age of Subjects
44.6% 40
35.3% 20
18.6%
Diet
Sulfonylurea
Metformin
Combination
Brown JB et al. Diabetes Care. 2004;27:

28. Barriers to Glycemic Control Hypoglycemia
Risk Factors
Outcomes
Use of insulin or secretagogues [e.g. sulfonylureas (SUs)]
Drugs that affect SU levels*
Advanced age
Duration of diabetes
Renal failure
Liver failure
Hypothyroidism, hypoadrenalism
Missed/irregular meals
Advanced cancer, malnutrition
Hypoglycemia unawareness
Increase glucose variability
Decreased intensiveness of glucose control
Employment challenges
Loss of confidence
Loss of independence
Personal and family stress
Increased CV events
Increased rates of dementia
* aspirin, allopurinol, trimethoprim, warfarin

29. Barriers to Glycemic Control Weight Gain is a Common Side Effect of Many Oral Agents for T2DM
Oral antidiabetic agent*
Weight change (kg)
Metformin1-3
SUs1-4
TZDs4-6
Meglitinides4,7,8
Metformin + SU1-3
Metformin + TZD5,6,9
*Data are not from head-to-head studies
1. Bristol-Myers Squibb. Glucophage® full prescribing Information
6. GlaxoSmithKline. Avandia® full Prescribing Information
2. Bristol-Myers Squibb. Glucovance® full prescribing Information
7. Novartis. Starlix® full Prescribing Information
3. Bristol-Myers Squibb. Metaglip® full Prescribing Information
8. Novo Nordisk. Prandin® full Prescribing Information
4. Malone M. Ann Pharmacother. 2005;39:
9. GlaxoSmithKline. Avandamet® full Prescribing Information
5. Eli Lilly. Actos® full Prescribing Information

30. III. Current T2DM Treatment Options and Their Places in Guideline-based Care

31. ADA/ACC/AHA Position Statement on HbA1C Goals Individualized for Your Patient
Most non-pregnant adults <7%
For selected individuals, might reasonably suggest even lower if this can be achieved without significant hypoglycemia
Short duration of diabetes
Long life expectancy
No significant CVD
Less stringent goal for patients with:
History of severe hypoglycemia
Limited life expectancy
Advanced micro- or macrovascular complications, extensive comorbid conditions
Longstanding diabetes in which the general goal is difficult to attain despite diabetes self-management, etc.
American Diabetes Association. Diabetes Care. 2012;35(Suppl 1):S11-S63.

32. Medications for Hyperglycemia in Type 2 Diabetes: ADA 2014 Guidelines
GLP = glucagon-like peptide
American Diabetes Association. Diabetes Care. 2014;37(suppl 1):S14-S80.

33. The Pathophysiology of Type 2 Diabetes Involves Multiple Dysfunctions
Insulin secretion β
Glucose production
Glucose uptake
Glucagon secretion α
Hyperglycemia
Incretin effect
Lipolysis
Neurotransmitter function
Glucose reabsorption
Glucose reabsorption
DeFronzo RA. Diabetes. 2009;58:
DeFronzo RA. From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus. Diabetes. 2009;58(4):
Aronoff SL, Berkowitz K, Shreiner B, Want L. Glucose metabolism and regulation: beyond insulin and glucagon. Diabetes Spectrum. 2004;17(3):
Gerich JE. Role of the kidney in normal glucose homeostasis and in the hyperglycaemia of diabetes mellitus: therapeutic implications. Diabet Med. 2010;27(2): 33

34. Incretins
Gut-derived hormones, secreted in response to nutrients, that potentiate insulin secretion and suppress glucagon secretion in a glucose dependent fashion
Many other tissue effects
Two predominant incretins
Glucagon-like peptide-1 (GLP-1)
Glucose-dependent insulinotropic peptide (GIP)
Rapidly inactivated by dipeptidyl peptidase-4
Incretin effect is impaired in type 2 diabetes
1. Holst JJ et al. Diabetes. 2004;53(suppl 3):s197-s204.
2. Meier JJ et al. Diabetes Metab Res Rev. 2005;21:

35. Oral glucose (50 g) or isoglycemic infusion
Incretin Effect
Difference in the Insulin Response to Oral vs IV Glucose
2.0
1.5
1.0
0.5
0.0
IV glucose
Oral glucose
Oral glucose (50 g) or isoglycemic infusion *
200
100
C-Peptide (nmol/L)
Plasma Glucose (mg/dL) 60
120
180 60
120
180
Time (min)
Time (min)
Reprinted with permission from Nauck MA et al. J Clin Endocrinol Metab. 1986;63: © 1986 The Endocrine Society.

36. Type 2 Diabetes Patients
Reduced Incretin Effect in Type 2 Diabetes Patients 80 60 40 20
Insulin (mU/L)
Time (min)
Type 2 Diabetes Patients *
Control Subjects
Intravenous Glucose
Oral Glucose
Reprinted with permission from Nauck M et al. Diabetologia. 1996;29:46-52. 36

37. Role of Incretins in Glucose Homeostasis
4/21/2017 1:09 AM
Role of Incretins in Glucose Homeostasis
Ingestion of food
Beta cells
Alpha cells
Release of gut hormones — Incretins1,2
Pancreas2,3
Glucose-dependent  Insulin from beta cells
(GLP-1 and GIP)
Glucose uptake by muscles2,4
Glucose production by liver
Blood glucose
Glucose dependent
 Glucagon from alpha cells
(GLP-1)
GI tract
Active
GLP-1 & GIP
DPP-4 enzyme
Inactive GIP
Inactive GLP-1
Purpose:
To demonstrate how the incretin pathway is part of the normal
physiology of glucose homeostasis.
Takeaway:
After food ingestion, incretins stimulate insulin release from beta cells and suppress glucagon release from alpha cells in a glucose-dependent manner, resulting in downstream effects that regulate glucose homeostasis.
DPP-4 = dipeptidyl-peptidase 4
Kieffer TJ, Habener JF. Endocr Rev. 1999;20:
Drucker DJ. Diabetes Care. 2003;26:
Ahrén B. Curr Diab Rep. 2003;2:
Holst JJ. Diabetes Metab Res Rev. 2002;18:
References
1. Kieffer TJ, Habener JF. The glucagon-like peptides. Endocr Rev. 1999;20:876–913.
2. Ahrén B. Gut peptides and type 2 diabetes mellitus treatment. Curr Diab Rep. 2003;3:365–372.
3. Drucker DJ. Enhancing incretin action for the treatment of type 2 diabetes. Diabetes Care. 2003;26:2929–2940.
4. Holst JJ. Therapy of type 2 diabetes mellitus based on the actions of glucagon-like peptide-1. Diabetes Metab Res Rev. 2002;18:430–441.
5. Nauck MA, Kleine N, Ørskov C, Holst JJ, Wilms B, Creutzfeldt W. Normalization of fasting hyperglycaemia by exogenous glucagon-like peptide 1 (7-36 amide) in type 2 (non-insulin-dependent) diabetic patients. Diabetologia. 1993;36:741–744.

38. Treatment Strategies Involving the Incretin System
GLP-1 receptor agonists
Exenatide, liraglutide
Long-acting exenatide QW, albiglutide, dulaglutide
Subcutaneous injection
DPP-4 enzyme inhibitors
Molecule selectivity inhibits activity of DPP-4
Sitagliptin, saxagliptin, linagliptin, alogliptin
Oral
Incretin enhancers
Lack “high” GLP-1 effects
Physician’s Desk Reference. Montvale, NJ. Thomson PDR; 2013.

39. GLP-1 Receptor Agonists
Injectable
Efficacy
Primary effect is on post-meal glucose levels
Longer duration of action, better FPG and A1C lowering
HbA1C lowering: 0.5%-2.0%
Potential for weight loss
Safety
Major side effect: nausea/vomiting
No added hypoglycemia unless used with secretagogue or insulin
C-cell hyperplasia and medullary cancer in rodents
Pancreatitis – not seen in large database analyses
Physician’s Desk Reference. Montvale, NJ. Thomson PDR; 2013.

40. DPP-4 Inhibitors Efficacy: HbA1C reduction: ~0.5-0.9% Weight neutral
Renal dosing adjustment – not for linagliptin
Safety:
No added hypoglycemia unless used with sulfonylurea
Rare instance of Stevens-Johnson
Evidence for no increased CV risk (saxagliptin and alogliptin)1,2
No increased risk of pancreatitis or pancreatic cancer3
Scirica BM et al. New Engl J Med. 2014;369:
White WB et al. New Engl J Med. 2013;369:
Egan AG et al. New Engl J Med. 2014;370:

41. Short, Long, and Very Long-acting GLP-1 RA
Parameters
Short-acting
Long-acting
Very Long-acting
Compounds
Exenatide
Liraglutide
Albiglutide, Dulaglutide,
Exenatide QW
Half-life
2-5 hours
12-14 hours
>1 week
Frequency of administration
Twice daily
Once daily
Once weekly
HbA1C reduction
0.7–1.7%
0.8–1.8%
% albiglutide
0.7–1.6% dulaglutide
1.3%-1.9% exenatide QW
FBG levels reduction
Modest
Strong
PP hyperglycemia
Glucagon secretion
Reduction
Gastric emptying rate
Deceleration
No effect
Blood pressure
Body weight reduction
1-5 kg
2-4 kg kg
FBG = fasting blood glucose; PP = postprandial; QW = once weekly
Meier JJ. Nat Rev Endocrinol. 2012;8: Physician’s Desk Reference. Montvale, NJ. Thomson PDR; 2013.

42. Polling Question Baseline Survey
The DURATION 3 trial, which compared exenatide once weekly to insulin glargine in patients with type 2 diabetes who were failing oral antidiabetic therapy, reported all of the following outcomes, EXCEPT:
Significantly greater A1C reduction with exenatide
Higher rate of discontinuations due to adverse events with exenatide
Similar rates of hypoglycemia in the insulin glargine and exenatide groups
Weight loss with exenatide and weight gain with insulin glargine, a significant difference

43. Effects of Second-Line T2D Therapies as Add-on to Metformin
Meta-analysis of 39 RCTs (n=17,860)
Comparative A1C results:
GLP1-RA achieved greater reduction vs AGIs (-0.36%), DPP-4 inhibitors (-0.32%), glinides (-0.31%), SUs (-0.20%), and TZDs (-0.20%)
Reduction with GLP1-RA was comparable to basal and biphasic insulin
Other endpoints:
Hypoglycemia was more likely associated with SUs, glinides, basal insulin, and biphasic insulin; not with GLP1-RA
Weight increased with SUs, glinides, TZDs, basal insulin, and biphasic insulin
Weight reduced with AGIs and GLP-1 analogues
Liu SC et al. Diabetes Obes Metab. 2012;14:

44. DURATION-5: Mean A1C Reduction and Percent at A1C Targets
Randomized trial of once-weekly vs twice-daily exenatide in 252 patients on metformin (71%-80%), SU (28%-31%), and/or TZD (10%-17%)
Baseline HbA1C ExBID ExQW
<9.0% 72% 70%
≥9.0% 28% 30%
Blevins T et al. J Clin Endocrinol Metab. 2011;96:

45. DURATION-5: Adverse Events
Exenatide BID (n=123)
Exenatide QW (n=129)
Nausea
35%
14%
Diarrhea
4.1%
9.3%
Upper respiratory infections
7.0%
Injection-site erythema
2.4%
5.4%
Vomiting
8.9%
4.7%
Headache
8.1%
Dizziness
6.5%
2.3%
Blevins T et al. J Clin Endocrinol Metab. 2011;96:

46. HARMONY 7: Change in A1C Over 32 Weeks
Randomized trial of once-weekly albiglutide vs once-daily liraglutide in 422 patients inadequately controlled on oral anti-diabetes drugs
-0.98%
-0.79%
P=0.08 for non-inferiority
Baseline HbA1C
Albiglutide – 8.1%
Liraglutide – 8.1%
Pratley RE et al. Lancet Diabetes Endocrinol. 2014;2:

47. HARMONY 7: Adverse Events
Albiglutide (n=404)
Liraglutide (n=408)
P Value
Diarrhea
14.9%
13.5%
0.57
Upper respiratory infection
10.4%
11.0%
0.77
Nausea
9.9%
29.2%
<0.0001
Injection-site reaction
6.9%
1.2%
Urinary tract infection
6.2%
5.6%
0.74
Headache
5.4%
0.97
Vomiting
5.0%
9.3%
0.0154
Withdrawal for AEs
2.7%
0.2% NR
-0.79%
Pratley RE et al. Lancet Diabetes Endocrinol. 2014;2:

48. DURATION-3: Effects on A1C After 3 Years
Randomized trial of once-weekly exenatide vs insulin glargine in 456 patients inadequately controlled on glucose-lowering drugs
-1.01%
-0.81%
P=0.03
Baseline HbA1C
Exenatide 8.3%
Glargine 8.3%
Diamant M et al. Lancet. 2014;2:

49. DURATION-3: Other Endpoints
-2.49 kg
+2.01 kg
Overall hypoglycemia rate:
Insulin glargine: 0.9 events/pt year
Exenatide: 0.3 events/pt year
More GI events with exenatide vs glargine: nausea (15% vs 2%), diarrhea (14% vs 7%), vomiting (6% vs 3%), constipation (5% vs 3%)
More discontinuations due to AEs with exenatide vs glargine: 9% vs 2%
Diamant M et al. Lancet. 2014;2:

50. Odds ratio (95% confidence interval)
Other Adverse Effects with GLP-1 RAs Data from Exenatide and Liraglutide Studies*
Event
Odds ratio (95% confidence interval)
P value
Hypoglycemia
2.92 ( )
0.002
With SUs
4.62 ( )
0.001
Without SUs
1.37 ( )
0.34
Cardiovascular events
0.99 ( )
0.98
*Meta-analysis of predominantly exenatide and liraglutide studies
n=5429 receiving GLP-1 receptor agonists, n=3053 active comparators or placebo
Monami M et al. Eur J Endocrinol. 2009;160:

51. Incretin-related Drugs and Pancreatitis Risk
There has been much discussion regarding the safety of incretin agents (e.g. regarding exenatide, liraglutide, sitagliptin)
Recent published and unpublished data report an increased risk of pancreatitis and pancreatic duct metaplasia in T2DM patients receiving incretins
FDA investigated potential pancreatic toxicity associated with incretins
FDA stated that available data do not confirm recent concerns over an increased risk for pancreatic side effects with GLP-1 therapies
NIDDK experts also concluded that there is little evidence of increased risk for pancreatic cancer with GLP-1 agents
FDA study regarding pancreatitis and pancreatic cancer with incretins is ongoing
FDA. FDA Drug Safety Communication: FDA investigating reports of possible increased risk of pancreatitis and pre-cancerous findings of the pancreas from incretin mimetic drugs for type 2 diabetes Available at:
Brooks M. FDA sides with EMA on incretin diabetes drugs Available at:

52. Pancreatitis Recommendations for Health Care Professionals
Pancreatitis is more common in patients with diabetes1
Recommendations for monitoring and management2-4
Observe patients for symptoms of acute pancreatitis (persistent severe abdominal pain that may be accompanied by vomiting)
Discontinue drug if pancreatitis is suspected  
Do not restart drug if pancreatitis is confirmed
Consider other anti-hyperglycemic therapies in patients with a history of pancreatitis
Yadav D et al. Gastroenterology. 2013;144:
Byetta® fact sheet. Available at:
US FDA Web site; Exenatide (marketed as Byetta) – Healthcare Professional Sheet text version (8/2008). Available at:
Victoza [package insert]. Princeton, NJ: Novo Nordisk Inc.; 2011.

53. Summary of GLP-1 Receptor Agonist Therapy in T2D
Incretin system is a powerful physiologic system impacting post-meal BG control
Defective in T2D
Intriguing constellation of clinical effects
Postprandial glucose control
Weight loss
Low risk of hypoglycemia
Potential for weekly dosing

54. IV. Practical Considerations

55. Polling Question Baseline Survey
A recently reported analysis of compliance data from the HARMONY trials, which evaluated the once-weekly GLP-1 inhibitor albiglutide, reported what finding?
Greater compliance with placebo injection than albiglutide injection
Greater compliance with oral antidiabetic drugs compared to albiglutide injection
Lower compliance with oral antidiabetic drugs compared to placebo injection or albiglutide injection
No differences in compliance across all groups, including active and placebo and oral and injectable agents

56. Correlation Coefficient
Psychosocial Predictors of Poor Adherence to Insulin Therapy in Patients with T2D
Survey of 1,530 adults with T2D treated with insulin
35% reported ≥1 days of insulin omission per month (mean: 3 days)
Insulin omission more common in patients who were male (P<0.001), younger (P<0.0001), and had more frequent hypoglycemia (P<0.05)
Psychosocial/Behavioral Correlates of Insulin Omission
Prevalence or Mean
Correlation Coefficient
P Value
Adherence to non-medication regimens (number of succesful behaviors; range, 0-4)
2.4*
-0.12
<0.001
Insulin regimen adherence perceived as “important”
99.0%
-0.05
<0.05
Injections perceived to affect lifestyle
43.3%
+0.06
Injection difficulty (from 1 “very easy” to 4 “very difficult”)
1.8
+0.07
Satisfaction with ability to choose when to take injections (from 1 “very dissatisfied” to 4 “very satisfied”)
3.3
-0.07
<0.01
Peyrot M et al. Diabetes Obes Metab. 2012;14:

57. Strategies to Improve Patient Acceptance and Self-management with GLP-1 Agonist Therapy
Patient Barrier
Recommendations
Needle phobia
Familiarize patients with pen devices or delivery kits
Avoid using the word “shot”
Differentiate between SC and IM injections
Have patients self-inject the first dose in the office; alternatively, just use the needle
Poor motivation
Discuss benefits such as weight loss and low hypoglycemia risk
Encourage patients to perform SMBG for 1-2 weeks after initiating to see reductions in FBG and PPG levels
Involve a dietitian to help patients identify strategies to maximize the potential for weight loss
Nausea
Before initiation, educate patients that transient nausea is possible
Dose-escalate exenatide BID or liraglutide, but not exenatide QW, as described in prescribing information
Consider lengthening the time over which the dose is escalated
Administer exenatide BID <60 minutes before the meal
Temporarily reduce the dose
Counsel patients to stop eating when they feel full
Avoid administering the medication close to a large or high-fat meal
FBG = fasting blood glucose; PPG = postprandial glucose; SMBG = self-monitoring of blood glucose.
Reid T. Clin Diabetes. 2013;31:

58. Compliance with T2D Medications: Injection vs Oral Therapy % of Patients with <80% Compliance
HARMONY 3 Trial (Week 156)
HARMONY 5 Trial (Week 156)
HARMONY 8 Trial (Week 52)
Leiter LA et al. ADA 2014 Annual Meeting. Abstract 994-P.

59. New Delivery Options: Exenatide Suspension QW with Single-use Auto-injector Pen
28-week open-label study of exenatide twice daily (ExBID) vs exenatide suspension given once-weekly via single-use auto-injector pen (ExSQW) in patients with inadequately controlled T2D
ExBID (n=148)
ExSQW (n=229)
Change in A1C
-1.02%
-1.39%*
Change in body weight
-1.89 kg
-1.48 kg
Adverse events
Nausea
21.2%
9.6%
Diarrhea
11.6%
5.2%
Vomiting
6.2%
3.5%
Injection-site nodules
0.7%
12.7%
*P = vs ExBID
Wysham CH et al. EASD 2014 Annual Meeting. Abstract 244.

60. Case 1: Revisited
Marcus is a 33-year-old overweight man with 4-year history of T2DM
Current medications: metformin 1000mg BID, glipizide 10mg QD
He has gained 15 lbs in 11 months; current BMI: 28.3 kg/m2
Lab evaluation
HbA1C: 8.2%
BP: 172/85 mm Hg
Total cholesterol: 242 mg/dL
Patient concerns
Robert reveals that he has not been adherent to his T2DM medications because he was “tired of taking so many pills every day”
He has experienced episodes of shakiness and extreme hunger before lunch and dinner
He is now worried about his health because his father recently suffered a fatal MI at age 57

61. Case Discussion Individual HbA1C goal? Treatment priorities
Improved glycemic control
Weight neutral or associated with weight loss
Low risk of hypoglycemia
Improved cardiovascular risk profile

62. Summary
Poorly controlled hyperglycemia significantly increases the risk of microvascular and macrovascular complications
Despite effective therapies, <30% of patients with T2DM meet the treatment goal of A1C <7.0%
Patients require individualized therapy for effective glycemic control
Consider the effects of medications on T2DM pathophysiology, body weight, hypoglycemic risk, and other endpoints
Utilize a collaborative approach to T2DM management
Empower the patient through patient education on self-management strategies
Address barriers for optimal outcomes, including poor medication adherence and injection-related barriers

63. Participant CME Evaluation
Please take out the Participant CME Post-survey and Evaluation Form from the back of your packet.
If you are not seeking credit, we ask that you fill out the information pertaining to your degree and specialty, as well as the few post-activity survey questions measuring the knowledge and competence you have garnered from this program. The post-survey begins on page 1 of the evaluation form.
Your participation will help shape future CME activities.
Thank you for joining us today!