1. Barriers to Diabetes Control Mark E. Molitch, MD

2. NHANES: Achieving ADA Recommendations, 2003-2006 Individuals reaching glycemic control targets: HbA1c <7%57.1% Individuals achieving other ADA goals of therapy: BP <130/80 mm Hg45.5% LDL <100 mg/dL46.5% Only 12.2% of individuals met all 3 goals Abbreviations: BP, blood pressure; HbA1c, glycosylated hemoglobin; LDL, low-density lipoprotein; NHANES, National Health and Nutrition Examination Survey Cheung BM, et al. Am J Med. 2009;122:443-453. 2

3. Treatment Algorithm for Type 2 Diabetes NOT glyburide, chlorpropamide NOT rosiglitazone Intensive insulin At diagnosis: Lifestyle + Metformin At diagnosis: Lifestyle + Metformin STEP 1 STEP 2 STEP 3 Add basal insulin Add sulfonylurea Add GLP-1 agonist Add pioglitazone HbA1c >7.0% Add DPP-4 inhibitor Abbreviations: DPP-4, dipeptidyl peptidase-4; GLP-1, glucagon-like peptide Nathan DM, et al. Diabetes Care. 2009;32:193-203. 4

4. Combination Therapy in Type 2 Diabetes: Decision Considerations HbA 1c efficacy  Reductions from baseline  Reaching target Synergy of mechanisms of action Side effects and toxicity profile Frequency and severity of hypoglycemia Effect on weight gain Avoiding polypharmacy and complex regimens Compliance and convenience Cost 5

5. Barriers to Diabetes Control Clinical inertia Financial Adverse effects of oral agents Insulin Fear of injections Fear of hypoglycemia Complexity of management Targets of treatment Need to adjust to individual patient Cultural 6

6. 6 Earlier and More Aggressive Intervention May Improve Treating to Target Compared With Conventional Therapy Monotherapy Uptitrate dose of monotherapy Add 2 nd and then 3 rd drug Add basal insulin then multiple insulin injections per day  Typical progression is to wait for HbA1c to reach 8–9% before moving to next step Moving more aggressively to more potent treatment can achieve goal of HbA1c of < 7% more quickly

7. 7 Advantages & Disadvantages of Type 2 Diabetes Medications Class (examples)PotencyRisk of hypoglycemiaWeightOther Sulfonylureas (glipizide, glyburide, glimepiride) +++ Greatest increase Less likely to maintain control as monotherapy Meglitinides (nateglinide, rapaglinide) +++ IncreaseShort acting Metformin++++ NeutralGI intolerance, rare lactic acidosis Thiazolidinediones (Rosiglitazone, Pioglitazone) +++ Greatest increase Fluid retention, worsen CHF, fractures. Risk of cardiac events. α-Glucosidase inhibitors (acarbose, miglitol) ++ DecreaseIntestinal gas, poor tolerance DPP-4 inhibitors ( sitagliptin, saxagliptin, linagliptin) ++ NeutralHeadache, risk of infection GLP-1 analogs (exenatide, liraglutide) ++ DecreaseInjection, GI effects Insulin+++ Greatest increase Injection AACE/ACE Diabetes Algorithm for Glycemic Control. Endrocr Pract. 2009;15:540-559.

8. Barriers to Insulin Therapy: Common Concerns Insulin therapy might cause: Worsening insulin resistance –But reduction of glucose toxicity improves resistance More cardiovascular risk –But reduction in glucose improves cardiovascular risk Weight gain –Yes, it does occur with improved metabolic efficiency Hypoglycemia –Very rare with type 2 diabetes –Common with type 1 diabetes as approaching optimum glycemic control 9

9. Rapidly growing populations High rates of type 2 diabetes and its complications Groups with unique culture, health beliefs, myths, and food preferences Diverse level of education and socio-economic status Insufficient culturally oriented diabetes care, education, and research programs Health care system and health professional barriers Cultural competency is key to approaching patients in a beneficial way Challenges and Opportunities in Minority Populations 10

10. Why We Cannot Always Extrapolate to Older Adults with Diabetes Heterogeneity Comorbid conditions –Functional limitations –Cognitive decline Polypharmacy Life expectancy versus –Time to incidence or progression of microvascular or macrovascular complications –Time to expected benefit of intervention 11