Challenges in the Management of T2DM—Exploring the Role of GLP-1 Receptor Agonists: Southern Region Frank Svec, MD, PhD Cl...
Challenges in the Management of T2DM—Exploring the Role of GLP-1 Receptor Agonists: Southern Region <ul><li>During today’s...
Frank Svec, MD, PhD Clinical Professor of Medicine Tulane University School of Medicine New Orleans, Louisiana
Ralph A. DeFronzo, MD Professor of Medicine Chief of Diabetes Division University of Texas Health Science Center at San An...
Program Goal <ul><li>Review the incidence and prevalence of type 2  diabetes mellitus (T2DM) </li></ul><ul><li>Evaluate ev...
Age-Adjusted Percentage of US Adults With Diagnosed Diabetes  Centers for Disease Control  and Prevention: National Diabet...
Incidence of T2DM <ul><li>Approximately 20 million individuals with T2DM in the United States a   </li></ul><ul><li>Additi...
Obesity Trends* Among US Adults *BMI ≥ 30 kg/m 2 , or about 30 lb overweight for 5’4” person. Centers for Disease Control ...
In your region, what percentage of your patients are obese?  <ul><li>A.  ≤ 25%  </li></ul><ul><li>B.  26%-50%  </li></ul><...
Initial Presentation <ul><li>49-year-old man with a 1-year history of T2DM </li></ul><ul><li>Waiter in the French Quarter;...
Case Presentations, Continued <ul><li>Cannot exercise </li></ul><ul><li>2 meals/day; snacks; drinks on the weekend </li></...
Polling Question #1 Results
T2DM Epidemic and Complications <ul><li>4000 new cases of diabetes are diagnosed daily </li></ul><ul><li>800 deaths from i...
Ethnic Disparities  <ul><li>Highest incidence of diabetes among American Indians a   </li></ul><ul><li>High incidence of d...
Diabetes and Cardiovascular Disease <ul><li>Increased incidence of atherosclerotic  cardiovascular complications a   </li>...
Challenges to Diabetes Care <ul><li>Complications among undiagnosed individuals  with diabetes  </li></ul><ul><li>Cost of ...
What is your greatest obstacle  to initiating therapy with GLP-1 receptor agonists? <ul><li>A.  Not being up-to-date on cu...
Next Steps <ul><li>Reinforce positive results; his BMI went down </li></ul><ul><li>Continue to reinforce the importance of...
Exenatide Sustained A1c Reductions  Over 82 Weeks 82-wk completer, N = 314; 82-wk ITT, N = 551; Mean ±SE. Time (week) Plac...
Durability of Exenatide: Weight Blonde L, et al.  Diabetes Obes Metab.  2006;8:436-447.
Effects of GLP-1 Agonists on Cardiovascular Risk Factors <ul><li>A subset achieved 3.5 years of exenatide exposure and had...
Follow-up <ul><li>Warn him about the potential gastrointestinal side effects of GLP-1 agonists (nausea, vomiting) and that...
Diabetes Algorithms and A1c Goal A1c Goal  American Diabetes Association ≤  7% American Association of Clinical Endocrinol...
American Diabetes Association <ul><li>Lowering A1c to below or around 7% has been  shown to reduce microvascular and macro...
Lifestyle + MET + PIO + SFU STEP 1 At diagnosis:  Lifestyle + MET STEP 2 STEP 3 OR If A1c ≥7% MET = metformin; PIO = piogl...
American Association of Clinical Endocrinologists/American College of Endocrinology Rodbard HW, et al.  Endocr Pract.  200...
Increased Hepatic Glucose  Production Impaired Insulin Secretion Hyperglycemia Decreased  Glucose Uptake TZDs GLP-1 analog...
Consensus Statements for T2DM Nathan DM, et al.  Diabetes Care . 2006;29:1963-1972. Nathan DM, et al.  Diabetes Care . 200...
Polling Question #2 Results
GLP-1 Receptor Agonists <ul><li>First-in-class exenatide approved in 2005 </li></ul><ul><li>Augment insulin secretion </li...
Insulin secretion β -cell neogenesis β -cell apoptosis Glucagon secretion Glucose  production Heart GI Tract Liver Muscle ...
Side Effects: GLP-1 Receptor Agonists  and DPP-4 Inhibitors Davidson JA.  Cleve Clin J Med . 2009;76(suppl5):S28-S38. GLP-...
Side Effects: Metformin and Thiazolidinediones  Seufert J, et al.  Clin Ther . 2004;26:805-818. Metformin Thiazolidinedion...
Next Steps Case 2 67-year-old woman with a long history of T2DM; babysits grandchildren; on sulfonylurea; A1c, 7.9% <ul><l...
Exenatide vs Insulin Glargine as  Add-on Therapy in T2DM A1c Level (%) * * * * * * 0 2 4 8 12 18 26 Change in Body Weight ...
Mean (SE): * P  < .005 SFU b MET + SFU c MET a * - 0.8 Change in  A1c (%) 247  245  241 8.5  8.5  8.5 Baseline n 113  110 ...
Buse JB, et al.  Diabetes Care . 2004;27:2628-2635. Effects of Exenatide in Sulfonylurea-Treated Patients: Weight
Follow-up <ul><li>Illustrate the effects of binge alcohol consumption (hypoglycemia, pancreatitis risk) </li></ul><ul><li>...
Questions & Answers
Medullary Thyroid Cancer and Pancreatitis <ul><li>Liraglutide-induced medullary carcinoma is rare, but need to evaluate th...
Differences in Glycemic Control <ul><li>Genetic variation on response to treatment commonly seen </li></ul><ul><li>Further...
Challenges in the Management of T2DM—Exploring the Role of GLP-1 Receptor Agonists: Southern Region
Concluding Remarks <ul><li>Treatment of diabetes requires consideration of multiple risk factors </li></ul><ul><li>Obesity...
Summary: T2DM Is 2 Diseases <ul><li>Microvascular complications </li></ul><ul><li>Macrovascular complications </li></ul><u...
Thank you for participating in this Regional CME activity. Please take a few moments to read the brief assessment to help ...
Thank you for participating in this Regional CME activity. To proceed to the online CME test,  click on the   Earn CME Cre...
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Frank Svec, MD, PhD Clinical Professor of Medicine

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  • DISCUSSION Exenatide treatment resulted in sustained mean A1C reductions from baseline for both the 82-week completer cohort and 82-week ITT population BACKGROUND Patients in this analysis received either 5 or 10  g exenatide BID in the 30-week placebo-controlled trials, followed by 5  g BID for 4 weeks and 10  g BID thereafter All patients continued any preexisting treatment regimens of MET and/or SFU throughout the trials The 82-week ITT population (N = 551) consisted of those patients who had the opportunity to achieve 82 weeks of exenatide treatment The 82-week completer cohort (N = 314) consisted of those patients who were treated with exenatide for 82 weeks by the time of this analysis
  • Blonde et al. Diabetes, Obesity and Metabolism, 8, 2006, 436–447 Extension of open-label 30 wk trial to 82 wk.
  • DISCUSSION: Highlight the updated American Diabetes Association (ADA) consensus treatment algorithm for the treatment of type 2 diabetes (T2D) and exenatide’s place before basal insulin as a tier 2 approach. 1 An ADA consensus statement represents the authors&apos; collective analysis, evaluation, and opinion at the time of publication and does not represent official association opinion. CLICK #1: At diagnosis, recommend lifestyle interventions and check A1C every 3 months until A1C is &lt;7% and then at least every 6 months. CLICK #2: Course of therapy should be augmented if A1C ≥7%. Consider a Tier 1 or Tier 2 approach, with special consideration to lifestyle+MET+GLP-1 agonist (such as BYETTA ® ) to avoid greater risk of hypoglycemia and if patient is a good candidate for weight loss. When deciding between a Tier 1 or Tier 2 approach, lifestyle+MET+basal insulin should be your last treatment before moving to intensive insulin therapy (Build 3). REFERENCE: Nathan DM, et al. Diabetes Care. 2008;31(1):173-175. Q: How might the new ADA Consensus Treatment Algorithm affect your prescribing habits?
  • The question “What’s the next best therapy for a patient who is not achieving their glycemic goals on oral therapies?” is addressed by this study. It was published in The Annals of Internal Medicine this past November. In this particular trial, patients had A1Cs that averaged about 8.2--not extremely high--but not at goal. As you can see, either insulin glargine and exenatide resulted in improvements in glycemic control that were similar. The majority of patients were able to achieve an A1C of 7 or less. The answer to “What’s the next best drug to add?” is suggested by the difference between the two therapies with respect to patient weight. With exenatide, which again is in blue, you can see a substantial weight loss over the 26 weeks. However, in the insulin glargine group, as you would expect, there is a substantial weight gain. Obviously, if you are going to achieve the same glycemic control with weight loss rather than weight gain, most patients and clinicians would favor the agent that offers weight loss.
  • What’s the effect of exenatide on A1C? In phase III clinical trials--and these were the trials upon which the FDA based its approval— the results were compelling when exenatide was added to existing therapies. This was add-on therapy to metformin or to a sulfonylurea, or to metformin and sulfonylurea. And as you can see in each of the three trials, exenatide given in a 5mcg dose or 10mcg dose twice a day had a dose-dependent, beneficial effect on A1C. This benefit was independent of co-administration of either metformin or a sulfonylurea or a combination of both.
  • Diabetes Care 27:2628–2635, 2004 Less weight loss on SU, other results similar
  • Frank Svec, MD, PhD Clinical Professor of Medicine

    1. 1. Challenges in the Management of T2DM—Exploring the Role of GLP-1 Receptor Agonists: Southern Region Frank Svec, MD, PhD Clinical Professor of Medicine Tulane University School of Medicine New Orleans, Louisiana Kevan Chambers Announcer Medscape Diabetes & Endocrinology
    2. 2. Challenges in the Management of T2DM—Exploring the Role of GLP-1 Receptor Agonists: Southern Region <ul><li>During today’s discussion, we will present 2 interactive questions </li></ul><ul><li>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 </li></ul><ul><li>We hope to be able to answer at least some of your questions at the end of the program </li></ul><ul><li>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 </li></ul>
    3. 3. Frank Svec, MD, PhD Clinical Professor of Medicine Tulane University School of Medicine New Orleans, Louisiana
    4. 4. Ralph A. DeFronzo, MD Professor of Medicine Chief of Diabetes Division University of Texas Health Science Center at San Antonio San Antonio, Texas Staff Physician Department of Medicine Audie L. Murphy Division South Texas Veterans Health Care System San Antonio, Texas
    5. 5. Program Goal <ul><li>Review the incidence and prevalence of type 2 diabetes mellitus (T2DM) </li></ul><ul><li>Evaluate evidence-based guidelines for the management of diabetes </li></ul><ul><li>Focus on the role of glucagon-like peptide (GLP)-1 receptor agonists to help you tailor therapies to your patients with T2DM </li></ul>
    6. 6. 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%
    7. 7. Incidence of T2DM <ul><li>Approximately 20 million individuals with T2DM in the United States a </li></ul><ul><li>Additional 4-5 million individuals with undiagnosed diabetes a </li></ul><ul><li>60 million individuals with prediabetes (ie, impaired glucose tolerance, impaired fasting glucose) b </li></ul>a Centers for Disease Control and Prevention . 2008. b National Institute of Diabetes and Digestive and Kidney Diseases. 2008.
    8. 8. Obesity Trends* Among US Adults *BMI ≥ 30 kg/m 2 , 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%
    9. 9. In your region, what percentage of your patients are obese? <ul><li>A. ≤ 25% </li></ul><ul><li>B. 26%-50% </li></ul><ul><li>C. 51%-75% </li></ul><ul><li>D. ≥ 76% </li></ul>
    10. 10. Initial Presentation <ul><li>49-year-old man with a 1-year history of T2DM </li></ul><ul><li>Waiter in the French Quarter; 2 meals/day; weight conscious </li></ul><ul><li>Father died of coronary disease; older brother has coronary disease </li></ul><ul><li>Initial glycated hemoglobin (A1c) 9.1%; BMI = 29.5 kg/m 2 </li></ul>Case 1 <ul><li>A1c today 8.1%; BMI = 28.8 kg/m 2 ; LDL = 87 mg/dL; HDL = 33 mg/dL </li></ul><ul><li>Metformin 1000 mg twice daily and statin </li></ul><ul><li>Is concerned about heart disease; wants to lose weight; nervous about insulin </li></ul>
    11. 11. Case Presentations, Continued <ul><li>Cannot exercise </li></ul><ul><li>2 meals/day; snacks; drinks on the weekend </li></ul><ul><li>Does not check blood glucose values at home </li></ul><ul><li>BMI = 33.2 kg/m 2 ; A1c 7.9%; LDL = 138 mg/dL; SCr = 1.6 mg/dL; blood pressure = 137/88 mm Hg </li></ul><ul><li>ACE inhibitor/thiazide, sulfonylurea </li></ul>Case 2 <ul><li>67-year-old woman with a long history of T2DM </li></ul><ul><li>Cared for at Charity Hospital before Hurricane Katrina; moved to Mississippi; back to New Orleans </li></ul><ul><li>Old medical records lost </li></ul><ul><li>On insulin? </li></ul><ul><li>Lumbar disk disease and hypertension </li></ul>
    12. 12. Polling Question #1 Results
    13. 13. T2DM Epidemic and Complications <ul><li>4000 new cases of diabetes are diagnosed daily </li></ul><ul><li>800 deaths from individuals with T2DM daily </li></ul><ul><li>200 individuals with T2DM experience an amputation daily </li></ul><ul><li>50 individuals with T2DM develop blindness daily </li></ul>Rodgers G. http://www.nih.gov/news/radio/nov2009/20091110NDEP.htm
    14. 14. Ethnic Disparities <ul><li>Highest incidence of diabetes among American Indians a </li></ul><ul><li>High incidence of diabetes among Hispanics, Mexican Americans, and African Americans b,c </li></ul><ul><li>Lowest incidence of diabetes among whites </li></ul>a Lee ET, et al. Diabetes Care . 2002;25:49-54. b CDC. MMWR Morb Mortal Wkly Rep . 2004;53:941-944. c AHRQ. http://www.ahrq.gov/research/diabdisp.htm.
    15. 15. Diabetes and Cardiovascular Disease <ul><li>Increased incidence of atherosclerotic cardiovascular complications a </li></ul><ul><li>Incidence of myocardial infarction and stroke increased a </li></ul><ul><li>High cost of managing micro- and macrovascular complications b </li></ul>a Lotufo PA, et al. Arch Intern Med . 2001;161:242-247. b National Institute of Diabetes and Digestive and Kidney Diseases. 2008.
    16. 16. Challenges to Diabetes Care <ul><li>Complications among undiagnosed individuals with diabetes </li></ul><ul><li>Cost of medication </li></ul><ul><li>Patient propensity to lose weight </li></ul>
    17. 17. What is your greatest obstacle to initiating therapy with GLP-1 receptor agonists? <ul><li>A. Not being up-to-date on current safety and efficacy evidence supporting use of these agents in T2DM </li></ul><ul><li>B. Cost of medication/insurance/managed care issues </li></ul><ul><li>C. They offer no advantages over current antidiabetic agents </li></ul><ul><li>D. Unfamiliarity with placement of this class within treatment guidelines </li></ul><ul><li>E. Patients’ fear of injections or other patient-related factors </li></ul>
    18. 18. Next Steps <ul><li>Reinforce positive results; his BMI went down </li></ul><ul><li>Continue to reinforce the importance of diet and exercise </li></ul><ul><li>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 </li></ul><ul><li>Need to check serum creatinine level and liver function </li></ul><ul><li>Ask about history of pancreatitis </li></ul>Case 1 49-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
    19. 19. 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 (All patients 10 mg BID) Blonde L, et al. Diabetes Obes Metab . 2006;8:436-447. Blonde L, et al. Diabetes Obes Metab . 2006;8:436-447. 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% Change in A1c (%) 8.3% 8.4% Mean Baseline A1c 82-Week ITT 82-Week Completer
    20. 20. Durability of Exenatide: Weight Blonde L, et al. Diabetes Obes Metab. 2006;8:436-447.
    21. 21. Effects of GLP-1 Agonists on Cardiovascular Risk Factors <ul><li>A subset achieved 3.5 years of exenatide exposure and had serum lipids available for analysis (n = 151) </li></ul><ul><li>Triglycerides decreased 12% ( P = .0003) </li></ul><ul><li>Total cholesterol decreased 5% ( P = .0007) </li></ul><ul><li>LDL-C decreased 6% ( P < .0001) </li></ul><ul><li>HDL-C increased 24% ( P < .0001) </li></ul>Klonoff DC, et al. Curr Med Res Opin . 2008;24:275-286.
    22. 22. Follow-up <ul><li>Warn him about the potential gastrointestinal side effects of GLP-1 agonists (nausea, vomiting) and that they generally abate over time </li></ul><ul><li>Educate on the need to control glucose and weight </li></ul><ul><li>Review cardiovascular risk parameters </li></ul><ul><li>Test blood glucose twice daily – before breakfast, before dinner </li></ul><ul><li>DPP-4 inhibitors are a possibility, but they offer modest glucose lowering and are weight neutral </li></ul>Case 1
    23. 23. 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%
    24. 24. American Diabetes Association <ul><li>Lowering A1c to below or around 7% has been shown to reduce microvascular and macrovascular complications of T2DM </li></ul>American Diabetes Association. Diabetes Care . 2009;32(suppl1):S13-S61. Nathan DM, et al. Diabetes Care . 2006;29:1963-1972.
    25. 25. Lifestyle + MET + PIO + SFU STEP 1 At diagnosis: Lifestyle + MET STEP 2 STEP 3 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 + SFU Lifestyle + MET + Basal Insulin Tier 2: Less-well-validated therapies* Lifestyle + MET + PIO Lifestyle + MET + GLP-1 Agonist American Diabetes Association/European Association for the Study of Diabetes Tier 1: Well-validated core therapies* Lifestyle + MET + Intensive Insulin
    26. 26. American Association of Clinical Endocrinologists/American College of Endocrinology Rodbard HW, et al. Endocr Pract. 2009;15:540-559.
    27. 27. Increased Hepatic Glucose Production Impaired Insulin Secretion Hyperglycemia Decreased Glucose Uptake TZDs GLP-1 analogues DPP-4 inhibitors Sulfonylureas Thiazolidinediones Metformin  Metformin Thiazolidinediones _  Pathophysiologic Approach to Treatment of T2DM DeFronzo RA. Diabetes. 2009;58:773-795.
    28. 28. Consensus Statements for T2DM Nathan DM, et al. Diabetes Care . 2006;29:1963-1972. Nathan DM, et al. Diabetes Care . 2009;32:193-203. <ul><li>Consensus group of leading international endocrinologists and diabetologists with extensive clinical experience </li></ul><ul><li>Recent medical literature and all currently approved classes of medications should be considered </li></ul><ul><li>Common goal is to improve glucose control through individualization of therapy </li></ul>
    29. 29. Polling Question #2 Results
    30. 30. GLP-1 Receptor Agonists <ul><li>First-in-class exenatide approved in 2005 </li></ul><ul><li>Augment insulin secretion </li></ul><ul><li>Inhibit glucagon secretion </li></ul><ul><li>Lower fasting glucose and improve postprandial glucose profile </li></ul>Schnabel CA, et al. Vasc Health Risk Manag . 2006;2:69-77.
    31. 31. Insulin secretion β -cell neogenesis β -cell apoptosis Glucagon secretion Glucose production Heart GI Tract Liver Muscle Drucker DJ. Cell Metab . 2006;3:153-165. Brain Appetite Cardioprotection Cardiac output Stomach Gastric emptying Neuroprotection Glucose Uptake _ + Stomach GLP-1 GLP-1 Actions in Peripheral Tissue
    32. 32. Side Effects: GLP-1 Receptor Agonists and DPP-4 Inhibitors Davidson JA. Cleve Clin J Med . 2009;76(suppl5):S28-S38. GLP-1 Receptor Agonists DPP-4 Inhibitors Side effects Gastrointestinal Well tolerated Weight > 85% patients lose weight Weight neutral Administration Twice-daily injection Oral, once daily Other cardiac risk factors ↓ Triglycerides ↑ HDL ↓ Blood pressure Unknown
    33. 33. Side Effects: Metformin and Thiazolidinediones Seufert J, et al. Clin Ther . 2004;26:805-818. Metformin Thiazolidinediones Side effects Gastrointestinal Fluid retention, congestive heart failure, bone fractures Weight Weight neutral Weight gain Renal impairment Restricted > 1.4 mg/dL
    34. 34. Next Steps Case 2 67-year-old woman with a long history of T2DM; babysits grandchildren; on sulfonylurea; A1c, 7.9% <ul><li>Emphasize the importance of exercise and diet </li></ul><ul><li>Serum creatinine is high, so cannot use metformin </li></ul><ul><li>Insulin is a common next step and may be considered, but associated with weight gain and hypoglycemia </li></ul><ul><li>GLP-1 agonists should be considered to help lower glucose levels and may be associated with mild improvements in blood pressure and lipid profile </li></ul>
    35. 35. Exenatide vs Insulin Glargine as Add-on Therapy in T2DM A1c Level (%) * * * * * * 0 2 4 8 12 18 26 Change in Body Weight (kg) Heine RJ, et al. Ann Intern Med. 2005;143:559-569. Exenatide group (n = 275) Insulin glargine group (n = 260)
    36. 36. Mean (SE): * P < .005 SFU b MET + SFU c MET a * - 0.8 Change in A1c (%) 247 245 241 8.5 8.5 8.5 Baseline n 113 110 113 8.2 8.3 8.2 123 125 129 8.7 8.5 8.6 0.1 - 0.4 * - 0.8 * -0.5* - 0.9 * 0.1 0.2 - 0.6 * - 0.8 * MET = metformin; SFU = sulfonylurea a DeFronzo R, et al. Diabetes Care . 2005;28:1092-1100. b Buse JB, et al. Diabetes Care . 2004;27:2628-2635. c Kendall D, et al. Diabetes Care . 2005;28:1083-1091. Change in A1c Seen With Exenatide in Phase 3 Clinical Trials Placebo BID Exenatide 5 μg BID Exenatide 10 μg BID
    37. 37. Buse JB, et al. Diabetes Care . 2004;27:2628-2635. Effects of Exenatide in Sulfonylurea-Treated Patients: Weight
    38. 38. Follow-up <ul><li>Illustrate the effects of binge alcohol consumption (hypoglycemia, pancreatitis risk) </li></ul><ul><li>Another agent may help control hypertension </li></ul><ul><li>A statin may help lower LDL </li></ul><ul><li>Encourage home blood glucose monitoring </li></ul><ul><li>DPP-4 inhibitors can be considered, but insulin may cause unwanted weight gain </li></ul>Case 2
    39. 39. Questions & Answers
    40. 40. Medullary Thyroid Cancer and Pancreatitis <ul><li>Liraglutide-induced medullary carcinoma is rare, but need to evaluate the patient’s risk </li></ul><ul><li>Increase in incidence of pancreatitis in patients with T2DM, but unclear whether it is associated with use of exenatide </li></ul>Parks M, et al. N Engl J Med . 2010;362:774-777.
    41. 41. Differences in Glycemic Control <ul><li>Genetic variation on response to treatment commonly seen </li></ul><ul><li>Further studies are needed </li></ul>
    42. 42. Challenges in the Management of T2DM—Exploring the Role of GLP-1 Receptor Agonists: Southern Region
    43. 43. Concluding Remarks <ul><li>Treatment of diabetes requires consideration of multiple risk factors </li></ul><ul><li>Obesity/overweight is a prime factor in the development diabetes </li></ul><ul><li>Glucose control is important and can be accomplished without worsening adiposity </li></ul><ul><li>Discussion of side-effect profile of any medication ahead of time will enhance patient acceptance </li></ul>
    44. 44. Summary: T2DM Is 2 Diseases <ul><li>Microvascular complications </li></ul><ul><li>Macrovascular complications </li></ul><ul><li>Two distinct pathogenic sequences </li></ul><ul><li>Two distinct clinical presentations </li></ul>
    45. 45. Thank you for participating in this Regional CME activity. Please take a few moments to read the brief assessment to help us assess the effectiveness of this medical education activity.
    46. 46. Thank you for participating in this Regional CME activity. To proceed to the online CME test, click on the Earn CME Credit link on this page.

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