Breaking the Cycle: Using Incretin-Based Therapies to Overcome Clinical Inertia in Type 2 Diabetes

Transcription

1 Breaking the Cycle: Using Incretin-Based Therapies to Overcome Clinical Inertia in Type 2 Diabetes Taking It to the Next Level: Pearls for Your Clinical Practice Thursday, April 23, :00 AM - 8:00 AM Philadelphia Marriott Downtown R. Daniel Pollom, MD Medical Director, Diabetes Care Center Community Health Network The Indiana Heart Hospital Indianapolis, Indiana 68-year-old white male Diagnosed with type 2 diabetes 15 years ago A1C = 7.8% Glycemic control relatively good (A1C 7.1) until last 3 years (corresponding with retirement) Overweight 220 lb BMI = 29.8 kg/m 2 Hypertension (144/85 mm Hg) Retinopathy (moderate nonproliferative) History of myocardial infarction Other considerations Wife died several months ago May make complicated therapy difficult History of symptomatic hypoglycemia with SU Irregular blood glucose monitoring What is your greatest concern for this patient? 1. Poor glycemic control 2. Uncontrolled blood pressure 3. Poor medication adherence 4. Suboptimal self-management 5. Depression 6. Other Physician Approaches to Overcoming Clinical Inertia Elicit feedback on patient s performance from specialist partners Implement patient-specific reminders Utilize standardized flow sheets Delegate responsibilities to other healthcare providers Joy SV. Diabetes Educ. 2008;34:54S-59S. Phillips LS, et al. Diabetes Care. 2005;28: Ziemer DC, et al. Arch Intern Med. 2006;166: Lin D, et al. Can Fam Phys. 2007;53:

2 Patient-Based Approaches to Overcoming Clinical Inertia Proactive contact, surveillance, and reminders Motivational techniques Improve communication Verify recall and comprehension regarding new information Clarify treatment benefits Minimize adverse effects Discuss adverse effects Adjust regimen Simplify regimen(s) Minimize cost Joy SV. Diabetes Educ. 2008;34:54S-59S. Rubin RR. Am J Med. 2005;118:27S-34S. Pathophysiology-Centered Approaches to Overcoming Clinical Inertia Initiate treatment early Combine agents to address multiple pathophysiologic defects Focus on pathogenic abnormalities, not just A1C DeFronzo R Banting Memorial Lecture. Available at: On proactive questioning, Jim admits that he often forgets to take his medications He s been very down and not himself since his wife died His wife used to remind him to take his medications His wife also used to get on [him] about exercising and eating right Now he doesn t exercise, even though his cardiologist has prescribed cardiac rehabilitation Which of the following referrals would you provide first for this patient? 1. Mental health specialist 2. Diabetes educator 3. Ophthalmologist 4. Cardiologist How would you adjust this patient s medication? 1. Intensify glycemic control 2. Intensify blood pressure medication 3. Prescribe antidepressant 4. Several of the above 5. No change Jim and his physician discuss current problems and ways to address them Depression Problem Poor self-management Poor medication adherence Steps to Address Problem Sessions with diabetes educator Attend cardiac rehabilitation sessions Set up reminders Implement pill organizers Referral to mental health specialist Consider antidepressant Jim and his physician agree to the following first steps: Sessions with diabetes educator Attend cardiac rehabilitation sessions Try pill organizer Prescription for antidepressant 2

3 1 Month Later Blood pressure: 140/80 mm Hg Previous A1C = 7.8% Jim has measured his blood glucose a few times in the past month In the morning, before breakfast FPG seems to be in control Lowest he remembers: 95 mg/dl Highest he remembers: 105 mg/dl Fluoxetine: 20 mg, by mouth, once daily (filled but not started) 1 Month Later Cardiac rehabilitation was a good choice for him Finds the exercise bike relaxing and enjoys the people at the facility Diabetes educator Showed him how to measure his blood glucose Understands that staying on top of things really can help, even if he doesn t feel a big difference from day to day Reports better medication adherence due to Pill organizer Diabetes education Filled fluoxetine prescription but has not started it Would like to try a grief counseling group recommended by friends Summary of Guideline Recommendations for the Use of Incretin-Based Therapies ACE/AACE ADA/EASD Please see guideline pull-outs in program book for more details. GLP-1 Agonists* Therapeutic intensification for patients with A1C 6.5% Combination therapy (with metformin) when hypoglycemia or weight loss are concerns *Exenatide is currently the only approved GLP-1 analog. Sitagliptin is currently the only approved DPP-4 inhibitor. DPP-4 Inhibitors Monotherapy for patients with A1C = 6%-7% Combination therapy for patients with A1C 7% Not included in algorithm May be appropriate in some patients ACE/AACE Diabetes Road Map Task Force. Road maps to achieve glycemic control in type 2 diabetes mellitus. Available at: Nathan DM, et al. Diabetes Care. 2009;32: Case Study: Guidelines and ACE/AACE Recommendations Patient currently receiving combination therapy Intensification options Add insulin Near-normal FPG and elevated A1C suggest elevated postprandial glucose Addition of prandial insulin would be appropriate Combine with approved oral agents Add GLP-1 agonist for patients on SU, TZD, and/or metformin ACE/AACE Roadmap. Available at: Case Study: Guidelines and ADA/EASD Recommendations Patient currently on lifestyle + MET + PIO Alternative option: lifestyle + MET + GLP-1 agonist Intensification options MET + PIO + SU MET + basal insulin How would you intensify Jim s glycemic control therapy? 1. Add insulin 2. Add SU 3. Add DPP-4 inhibitor 4. Add GLP-1 agonist Nathan DM, et al. Diabetes Care. 2009;32:

4 DPP-4 Inhibitors vs GLP-1 Agonists Characteristic GLP-1 activity enhanced GIP activity enhanced Fluctuations in physiologic range Effect limited by endogenous secretion Low risk of hypoglycemia Sustained effect Durable* Superior tolerability vs oral agents Nausea Weight loss Oral Injectable Once daily DPP-4 Inhibitors GLP-1 Agonists? What characteristic would make a DPP-4 inhibitor a particularly good option for Jim? 1. Weight neutral 2. Dosing (oral, once daily) 3. Favorable tolerability profile 4. Low risk of hypoglycemia *Efficacy maintained over extended periods of time based on results of animal studies.?, long-acting agents in late clinical development. What therapeutic characteristic would make a GLP-1 agonist a particularly good option for Jim? 1. Level of anticipated glycemic control 2. Potential for weight loss 3. Low risk of hypoglycemia 4. Good postprandial glucose control 3 Months Later Action following previous appointment A GLP-1 agonist was prescribed at Jim s previous appointment Glycemic and blood pressure control are still not optimal A1C = 7.5% Blood pressure = 140/82 mm Hg Exenatide: 10 mcg, injected, twice daily Fluoxetine: 20 mg, by mouth, once daily 3 Months Later Cardiac rehabilitation Jim has continued attending sessions Is attending grief counseling group Began fluoxetine because some people in his group told him it was helpful Nausea Management GLP-1 Agonists Gastrointestinal adverse effects are common Frequency and severity of nausea decrease over time in most patients Medication adherence Has not taken the GLP-1 agonist regularly because it makes him nauseous 4

5 Nausea Management Exenatide-Specific Recommendations Dose 5 mcg or 10 mcg? Inject within 1 minute to 1 hour before eating Exenatide not recommended in patients with severe gastrointestinal disease due to gastrointestinal adverse effects Nausea Management General Recommendations for GLP-1 Agonists Keep track of foods that cause nausea Eat smaller portions Nausea remedies Foods ginger, sugar-free mints, saltines, rice crackers, hot water sipped slowly Other deep breaths, long walks, anti-motion sickness wristbands Drugs Last resort? Over-the-counter antacids, nausea-relief liquid (glucose, fructose, and phosphoric acid), omeprazole Prescription promethazine, ondansetron, metoclopramide, prochlorperazine, etc How would you proceed? 1. Discuss ways to minimize adverse effects, particularly nausea 2. Discontinue GLP-1 agonist 3. Adjust GLP-1 agonist dose from 10 mcg to 5 mcg 4. Stress importance of medication adherence and reschedule appointment for next month Summary Clinical inertia Consider and address patient-related issues Intensify therapy promptly Use multiple interventions to address progressive, multifactorial pathophysiology DPP-4 inhibitors Oral Expected A1C decrease of approximately 0.5% to 1.0% Weight neutral Good side-effect profile Low risk of hypoglycemia GLP-1 agonists Injected Expected A1C decrease of approximately 1.0% Weight loss Low risk of hypoglycemia Question and Answer Session Incretin-Based Therapies in Practice 5