Frank Svec, MD, PhD Clinical Professor of Medicine Tulane University School of Medicine New Orleans, Louisiana Kevan Chambers Announcer Medscape Diabetes & Endocrinology Challenges in the Management of T2DM—Exploring the Role of GLP-1 Receptor Agonists: Southern Region
46
Embed
Frank Svec, MD, PhD Clinical Professor of Medicine Tulane University School of Medicine New Orleans, Louisiana Kevan Chambers Announcer Medscape Diabetes.
This document is posted to help you gain knowledge. Please leave a comment to let me know what you think about it! Share it to your friends and learn new things together.
Transcript
Frank Svec, MD, PhDClinical Professor of MedicineTulane University School of MedicineNew Orleans, Louisiana
Challenges in the Managementof T2DM—Exploring the Role of GLP-1 Receptor Agonists: Southern Region
Challenges in the Managementof T2DM—Exploring the Role of GLP-1 Receptor Agonists: Southern Region
• During today’s discussion, we will present 2 interactive questions
• You may also submit a question at any time during the program by using the “Ask a Question” box in the lower right-hand corner of your screen
• We hope to be able to answer at least some of your questions at the end of the program
• There will be a brief assessment at the end of the program asking about the changes that you might make in your practice, on the basis of your participation today. Your responses will help us to improve the content of this and future educational programs
Frank Svec, MD, PhDClinical Professor of MedicineTulane University School of MedicineNew Orleans, Louisiana
Ralph A. DeFronzo, MDProfessor of MedicineChief of Diabetes DivisionUniversity of Texas Health Science Center at San AntonioSan Antonio, Texas
Staff PhysicianDepartment of MedicineAudie L. Murphy DivisionSouth Texas Veterans Health Care SystemSan Antonio, Texas
Program Goal• Review the incidence and prevalence of type 2
diabetes mellitus (T2DM)
• Evaluate evidence-based guidelines for the management of diabetes
• Focus on the role of glucagon-like peptide (GLP)-1 receptor agonists to help you tailor therapies to your patients with T2DM
Age-Adjusted Percentage of US Adults With Diagnosed Diabetes
Centers for Disease Control and Prevention: National Diabetes Surveillance System. http://www.cdc.gov/diabetes/statistics.
1994 1999
2008
Missing Data <4.5%
4.5-5.9% 6.0-7.4%
7.5-8.9% ≥9.0%
aCenters for Disease Control and Prevention. 2008.bNational Institute of Diabetes and Digestive and Kidney Diseases. 2008.
Incidence of T2DM• Approximately 20 million individuals with T2DM in
the United Statesa
• Additional 4-5 million individuals with undiagnosed diabetesa
• 60 million individuals with prediabetes (ie, impaired glucose tolerance, impaired fasting glucose)b
Obesity Trends* Among US Adults
*BMI ≥ 30 kg/m2, or about 30 lb overweight for 5’4” person.Centers for Disease Control and Prevention. 2008.
1990 1999
2008
No Data
<10% 10–14% 15–19%
20–24% 25–29% ≥30%
In your region, what percentage of your patients are obese?
A. ≤ 25%
B. 26%-50%
C. 51%-75%
D. ≥ 76%
Initial Presentation
• 49-year-old man with a 1-year history of T2DM
• Waiter in the French Quarter; 2 meals/day; weight conscious
• Father died of coronary disease; older brother has coronary disease
Hospital before Hurricane Katrina; moved to Mississippi; back to New Orleans
• Old medical records lost• On insulin? • Lumbar disk disease and
hypertension
Polling Question #1 Results
Rodgers G. http://www.nih.gov/news/radio/nov2009/20091110NDEP.htm
T2DM Epidemic and Complications• 4000 new cases of diabetes are diagnosed daily
• 800 deaths from individuals with T2DM daily
• 200 individuals with T2DM experience an amputation daily
• 50 individuals with T2DM develop blindness daily
aLee ET, et al. Diabetes Care. 2002;25:49-54.bCDC. MMWR Morb Mortal Wkly Rep. 2004;53:941-944.cAHRQ. http://www.ahrq.gov/research/diabdisp.htm.
Ethnic Disparities • Highest incidence of diabetes among American Indiansa
• High incidence of diabetes among Hispanics, Mexican Americans, and African Americansb,c
• Lowest incidence of diabetes among whites
aLotufo PA, et al. Arch Intern Med. 2001;161:242-247.bNational Institute of Diabetes and Digestive and Kidney Diseases. 2008.
Diabetes and Cardiovascular Disease• Increased incidence of atherosclerotic
cardiovascular complicationsa
• Incidence of myocardial infarction and stroke increaseda
• High cost of managing micro- and macrovascular complicationsb
Challenges to Diabetes Care• Complications among undiagnosed individuals
with diabetes
• Cost of medication
• Patient propensity to lose weight
What is your greatest obstacle to initiating therapy with GLP-1 receptor agonists?
A. Not being up-to-date on current safety and efficacy evidence supporting use of these agents in T2DM
B. Cost of medication/insurance/managed care issues
C. They offer no advantages over current antidiabetic agents
D. Unfamiliarity with placement of this class within treatment guidelines
E. Patients’ fear of injections or other patient-related factors
Next Steps
• Reinforce positive results; his BMI went down
• Continue to reinforce the importance of diet and exercise
• GLP-1 agonist should be considered, given that his A1c is not at goal on metformin; he is worried about his heart, and wants to lose weight
• Need to check serum creatinine level and liver function
• Ask about history of pancreatitis
Case 149-year-old man with 1-year history of T2DM; on metformin; A1c, 8.1%; scared of insulin, worried about heart disease, and wants to lose more weight
Exenatide Sustained A1c Reductions Over 82 Weeks
82-wk completer, N = 314; 82-wk ITT, N = 551; Mean ±SE.
Time (week)
Placebo-controlled Open-label extension
0 10 20 30 40 50 60 70 80 90-1.5
-1.0
-0.5
0.0
-1.1% ± 0.1%
-0.8% ± 0.1%
Chan
ge in
A1c
(%)
(All patients 10 mg BID)
8.3%8.4%
Mean Baseline A1c
82-Week ITT82-Week Completer
Blonde L, et al. Diabetes Obes Metab. 2006;8:436-447.Blonde L, et al. Diabetes Obes Metab. 2006;8:436-447.
Blonde L, et al. Diabetes Obes Metab. 2006;8:436-447.
Durability of Exenatide: Weight
Effects of GLP-1 Agonists on Cardiovascular Risk Factors
• A subset achieved 3.5 years of exenatide exposure and had serum lipids available for analysis (n = 151)
Klonoff DC, et al. Curr Med Res Opin. 2008;24:275-286.
Follow-up
• Warn him about the potential gastrointestinal side effects of GLP-1 agonists (nausea, vomiting) and that they generally abate over time
• Educate on the need to control glucose and weight
• Review cardiovascular risk parameters
• Test blood glucose twice daily – before breakfast, before dinner
• DPP-4 inhibitors are a possibility, but they offer modest glucose lowering and are weight neutral
Case 1
Diabetes Algorithms and A1c Goal
A1c Goal
American Diabetes Association
≤ 7%
American Association of Clinical Endocrinologists
≤ 6.5%
European Association for the Study of Diabetes
≤ 6.5%
Emerging Evidence/Expert Opinion ≤ 6%
American Diabetes Association
American Diabetes Association. Diabetes Care. 2009;32(suppl1):S13-S61.Nathan DM, et al. Diabetes Care. 2006;29:1963-1972.
• Lowering A1c to below or around 7% has been shown to reduce microvascular and macrovascular complications of T2DM
Lifestyle + MET + PIO + SFU
Lifestyle + MET + PIO + SFU
STEP 1 At diagnosis: Lifestyle + MET
STEP 2
STEP 3 Lifestyle + MET + Intensive Insulin
OR
If A1c ≥7%
MET = metformin; PIO = pioglitazone; SFU = sulfonylurea*Validation based on clinical trials and clinical judgment Adapted from: Nathan DM, et al. Diabetes Care. 2009;32:193-203.
Lifestyle + MET + Basal Insulin
Lifestyle + MET + Basal Insulin
Lifestyle + MET + SFU
Lifestyle + MET + SFU
Lifestyle + MET + Basal Insulin
Lifestyle + MET + Basal Insulin
Tier 2: Less-well-validated therapies*
Lifestyle + MET + PIO
Lifestyle + MET + PIO
Lifestyle + MET + GLP-1 Agonist
Lifestyle + MET + GLP-1 Agonist
American Diabetes Association/European Association for the Study of Diabetes
Tier 1: Well-validated core therapies*
American Association of Clinical Endocrinologists/American College of Endocrinology