9/2/2016. Faculty. Utilizing Standards vs Innovations in Reaching Diabetes Goals: Point/Counterpoint. Disclosures. Learning Objectives.

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1 Faculty Utilizing Standards vs Innovations in Reaching Diabetes Goals: Point/ Daniel Einhn, MD, FACP, FACE Clinical Profess of Medicine University of Califnia, San Diego Medical Direct, Scripps Whittier Diabetes Institute Associate Edit, Journal of Diabetes President, Diabetes and Endocrine Associates La Jolla, Califnia Edward J. Shahady MD, FAAFP, ABCL Clinical Profess Family Medicine University of Flida Editial Board Member, Consultant President and Medical Direct Diabetes Master Clinician Program Inc. Fernandina Beach, Flida Disclosures Learning Objectives Dr. Einhn: Consultant/Research AstraZeneca, Halozyme, Janssen, Lilly, Novo Ndisk, Sanofi-aventis, Takeda, Adocia; Consultant: Glysens, Freedom- Meditech, Epitracker Speakers Bureau none; Shareholder Halozyme Dr. Shahady: Advisy Board Amgen, Janssen, Sanofi; Speakers Bureau Amgen Utilize registries to provide patient specific and population based repts as the foundation of team care and to help define planned visits, with the goal of reducing complications through goal achievement Recognize the alternative approach of innovation medication rather than lifestyle alone as the cnerstone of therapy in diabetes, by empowering the patient to engage less, not me Apply the point/counterpoint approach to show how two humanistic physicians perfm care from very different perspectives and strategies Goals Define planned visits Understand ientation and values of primary care clinicians compared to endocrinologist, cardiologist, and lipidologist Use registries to provide patient specific and population based repts as the foundation of team based care Reduce complications through goal achievement Diabetes Mellitus Most Difficult of All Chronic Diseases f Patient and Clinician! Patient Multiple medications, finger sticks, injections, frequent visits to your physician, exercise is no longer optional, food is now a potential enemy, counting carbs, fear of heart attacks, strokes, and premature death, adherence, fear of the unknown, Diabetes Distress and/ depression Clinicians Trying to please multiple masters, multiple responsibilities, conflicting guidelines, new medications, metabolic defects, pathophysiology, not enough time, confusing goals, various levels of literacy, limited compensation Shahady E, O Grady E. Consultant. 2015; 55(6):

2 Strategies f Improving Diabetes Care 2016 ADA Recommendations A patient-centered communication style that incpates patient preferences, literacy, numeracy, and cultural barriers Care should be aligned with components of the CCM to ensure productive interactions between a prepared, proactive practice team and an infmed, activated patient When feasible, care systems should suppt team-based care, community involvement, patient registries, and decision suppt tools to meet patient needs ADA = American Diabetes Association; CCM = chronic care model. American Diabetes Association. Diabetes Care. 2016;39(Suppl 1):S1-S112. Strategies f Improving Care Planned visits go from reactive to proactive Patient centered eliminate the wd non-compliant Understand ientation and values of primary care clinicians compared with endocrinologists, cardiologists, and lipidologists (A1c, LDL, BP) Use registries to provide patient specific and population based repts the framewk of the future Use registries as the foundation of team-based care to create a quality-iented culture Reduce complications through goal achievement A1c = hemoglobin A1C; LDL = -density lipoprotein; BP = blood pressure. American Diabetes Association. Diabetes Care. 2016;39(Suppl. 1):S1 S112. Planned Visit vs Reactive Care Planned Visit Develop a diabetes plan (list) with your team and seek patient agreement al patient to change goals to what he she thinks can be achieved Set goals f A1c, LDL, BP, and all other quality indicats Place all goals in writing and give patient a copy tell patient all future visits will be to review goals, achievements, and changes MA first one to see patients and review the goals at each visit protocol developed f MA to initiate some of the plans f goal achievement MA = medical assistant. Shahady E. Practical Diabetology. 2010;29: Planned Visit (cont) Planned Visit (cont) Shahady E. Practical Diabetology. 2010;29: Shahady E. Practical Diabetology. 2010;29:

3 Planned Visit (cont) Shahady E. Practical Diabetology. 2010;29: Is Non-Compliant a Useful Term? Patient Centered Eliminate the wd non-compliant Non-Compliant Use of the term gives us someone to blame f po control Who is non-compliant? The clinician, the patient, both, no one? Suggest the term non-compliant be eliminated from our vocabulary as it does little to help us fmulate solutions; it just places blame Suggest we substitute wds like barriers and system failure that impact effective quality care Seek patient and staff solutions Shahady E, O Grady E. Consultant. 2015; 55(6): Using Innovations to Simplify Living with Diabetes Mellitus Make it Easy on Your Patients and They ll Make it Easy on You 3

4 Patient Perspective Doct, I didn t come to you to be told to stop burning the candle at both ends. I came to you f me candles. Innovation f Success Accept the patients as they are, assuming they are already doing their best. Invite them to learn to improve diet, fitness, sleep, etc, but to avoid having their lack of success be an obstacle - Acknowledge that most people do not succeed with lifestyle modifications alone - Celebrate whatever lifestyle successes do happen Create a treatment regimen that minimally imposes on their usual daily routine, such as self-moniting, timing of food medications, etc As the prescriber, our overall role is to refer and empower lifestyle optimization, but our unique role is prescribing the most effective, safest, easiest medication regimen The Innovation-Focused Doct-Patient Relationship Free you up live a fullest life vs a burden of illness Do only the best you can perfection is not expected Diabetes is not your fault Diabetes is not shameful Together we will succeed We are partners, player/coach, etc I am not here to judge you even to grade you. We are in this together Medications in combinations will help you If lifestyle succeeds me than expected, we can always er medication Impact on Patient and Family Relief is palpable a cloud is lifted Roles in family and with the physician change deeply Now start from a position of positive psychology Surprise with simplicity, especially at first Creative ideas f lifestyle become generated by patient; you will be pleasantly surprised Me receptive to whatever medications may be required Adherence to everything greatly improves You are the first one who actually listened to me Impact on Patient and Family: Exceptions Need f regimented, judgmental, ly defined structure Need to do frequent self-moniting Need f aspirational targets: weight, exercise, etc Some eschew medications altogether Many eschew injectables at all costs Many will take a naturopathic approach (either instead in tandem, either telling you not) 4

5 Guide f Determining HbA1c Goal f Individual Patients Most Intensive Less Intensive Least Intensive HbA1c What Parameters Are Used to Individualize A1c Goals? Primary Care Clinicians vs Endocrinologists Psychosocial Less depression and distress, Depression, distress, few good suppt, motivated, resources, me resources, self-confident not confident, po suppt Hypoglycemia Risk Low High Frail/Life Expectancy Longer life expectance/active Less active/frail/needs help with ADL Combidities/CV Complications None Multiple/severe ADL = activities of daily living; CV = cardiovascular. American Diabetes Association. Clin Diabetes. 2015;33(2): Individualized Glycemic Goals Type 2 Diabetes Mellitus: Relative Weight Endocrinologists (250) vs Primary Care Clinicians (30) Individual Parameters Endocrinologists Primary Care Clinicians Rank Order Risk of Hypoglycemia 1 7 with Rx Life Expectancy 2 5 Combidities 3 4 Macrovascular and Advanced Microvascular Complications 4 6 Adherence and 5 2 Motivation Disease Duration 6 1 Resources and Suppt System 7 3 Cahn A, et al. Diabetes Care. 2015;38(12): Shahady E. Individual research communication, Changing the Diabetes Treatment Paradigm: Aggressive Treatment Late in the Course Is Too Late Lessons from ACCORD, ADVANCE, VADT, and NICE-GAR Glycemic control has less impact Hypoglycemia me common Hypoglycemia me dangerous Many me agents required Frequency of moniting must be intense Risk-benefit and cost-benefit unclear Primary Care Treatment Behavi Influenced by Timing of Disease Process Where in the Continuum of the Disease Does the Patient Present f Care? ACCORD = Action to Control Cardiovascular Risk in Diabetes; ADVANCE = Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation; VADT = Veterans Affairs Diabetes Trial; NICE-GAR = Nmoglycaemia in Intensive Care Evaluation Survival Using Glucose Algithm Regulation. 5

6 Diagnosis -cell function Incretin function Insulin resistance Insulin secretion Blood pressure and lipids Post-meal glucose Fasting glucose Natural Histy of Type 2 Diabetes Mellitus Glucagon Pre-diabetes Microvascular complications Macrovascular complications Type 2 diabetes mellitus Years from Diagnosis Nathan DM. N Engl J Med. 2002;347(17): Unger RH, Cherrington AD. J Clin Invest. 2012;122(1):4-12. Screening f Diabetes Mellitus Testing f all patients beginning at age 45 years If nmal results, repeat every 3 years Test at any age if patient has a BMI >25 >23 in Asian American patients A1c, FBS, 2 hours after a 75-g al glucose load Screen patients who are hypertensive Screen patients who have lipid abnmalities especially triglycerides and HDL BMI = body mass index; FBS = fasting blood sugar; HDL = -density lipoprotein. American Diabetes Association. Diabetes Care. 2016;39(Suppl 1):S13-S22. -Cell Failure in Type 2 Diabetes Mellitus: Prevention and Treatment Diagnosis Pre-diabetes Type 2 diabetes mellitus -cell function Incretin function Other metabolic defects -cell function decreased by lipotoxicity, glucotoxicity and inflammation stunned -α cells? Rx with lifestyle and some medications? Years from Diagnosis Halban PA, et al. Diabetes Care. 2014;37(6): A Clinically Relevant Composite Efficacy Endpoint Has Been Proposed Hypoglycemia No severe No symptomatic Glycemic control A1c <7% A1c 6.5% Weight No weight <1 kg weight Other Desirable Attributes Simplicity of daily living - Once daily, not timed, minimal set-up steps, etc. Lack of side effects Minimal self-moniting Minimal instruction Minimal titration Minimal office visits Minimal labaty testing Original criteria proposed by Zinman B, et al are shown in italics. Zinman B, et al. Diabetes Obes Metab. 2012;14:

7 Other Desirable Attributes (cont) Least number of pills (combinations desirable) Take advantage of rebate/coupon programs Patient family preference (f whatever reason) Affdability Accessibility in fmularies Minimal adverse media Registry Data Utilize Registries to Provide Patient Specific and Population Based Repts as the Foundation of Team Care ADA = American Diabetes Association. Shahady E. Personal Experience Diabetes Master Clinician Program. Registry Data (cont) Registry Data (cont) Staff and clinicians meet to review repts Have population repts f all parameters Review and create solutions f gaps in care ASA = aspirin. Shahady E. Personal Experience Diabetes Master Clinician Program. Shahady E. Personal Experience Diabetes Master Clinician Program. 7

8 Impact of Team Care 8-Month Period in 140 Patients Sat down as a team and discussed gap repts; created team decisions s, telephone calls (4 per day) Improved use of patient rept cards Protocols developed f MA to use f foot examination, microalbumin, and immunizations Shahady E. Personal Experience Diabetes Master Clinician Program. Innovation: When Cost Is the Driver Monotherapy Efficacy * Hypo risk Weight Side effects Costs Dual therapy Triple therapy Efficacy * Hypo risk Weight Side effects Costs Healthy eating, weight control, increased physical activity & diabetes education Metfmin neutral/loss GI / lactic acidosis If HbA1c target not achieved after ~3 months of monotherapy, proceed to 2-drug combination (der not meant to denote any specific preference - choice dependent on a variety of patient- & disease-specific facts): Metfmin Metfmin Metfmin Metfmin Metfmin Metfmin Sulfonylurea Thiazolidine- DPP-4 SGLT2 GLP-1 recept Insulin (basal) dione inhibit inhibit agonist intermediate intermediate est moderate risk risk neutral loss loss edema, HF, fxs rare GU, dehydration GI variable Metfmin Sulfonylurea If HbA1c target not achieved after ~3 months of dual therapy, proceed to 3-drug combination (der not meant to denote any specific preference - choice dependent on a variety of patient- & disease-specific facts): Metfmin Thiazolidinedione Metfmin DPP-4 Inhibit SGLT-2 Inhibit Metfmin Metfmin GLP-1 recept agonist Metfmin Insulin (basal) GLP-1-RA GLP-1-RA GLP-1-RA If HbA1c target not achieved after ~3 months of triple therapy and patient (1) on al combination, move to injectables, (2) on GLP-1 RA, add basal insulin, (3) on optimally titrated basal insulin, add GLP-1-RA mealtime insulin. In refracty patients consider adding SGL T2-i: Metfmin Figure 2C. An hyperglycemic Combination therapy injectable in T2DM: Basal Insulin Mealtime Insulin GLP-1-RA Minimiza therapy on of costs Inzucchi SE, et al. Diabetes Care. 2015;38: ;38: ; Qiu Diabetologia F, al. Eye 2015; /s (Lond). 2014;28(4): Using Medications to Minimize Cost Metfmin Extended release, combinations better tolerated Multiple additional benefits help adherence Pioglitazone (/- rosiglitazone) mg max minimizes edema and weight Reputation cleared: no cancer, heart, etc Glimepiride (/- glipizide ER up to 10 mg) 1-2 mg (4 max) minimizes Basal insulin vial and syringe NPH f fasting glucose - generic Biosimilar glargine now FDA approved NPH = neutral protamine Hagedn; FDA = Food and Drug Administration. Updated Metfmin: CKD Prescribing Guidelines (April 2016) Obtain egfr befe starting metfmin and annually, me frequently in those at risk of renal impairment (eg, elderly) Metfmin contraindicated in patients with an egfr <30 Starting metfmin in patients with an egfr between not recommended If egfr falls <45, assess the benefits and risks of continuing treatment D/C if egfr falls <30 Hold metfmin at the time of/befe iodinated contrast procedure if egfr 30-60; if h/o liver disease, alcoholism, heart failure; if intraarterial contrast. Recheck egfr 48 hours after procedure and restart if renal function stable FDA. Accessed April 8,

9 What the New Labeling Means Avoiding Cost f SGLT2 Inhibits 800,000 me people with egfr are eligible f prescriptions FDA did not include suggestion to er metfmin dose by 50% f EGFR <45, but that is a reasonable (if not evidence-based) suggestion F non-medicare patients $0-5 monthly co-pay renewable annually! Different plans cover different agents Applies to combinations with metfmin to er number of pills Applies to a combination with DPP4i (empagliflozin linagliptin) SGLT2 = sodium glucose cotranspter-2; DPP4i = dipeptidyl peptidase 4 inhibit. A Least-Expensive Regimen Alogliptin pioglitazone $4/month coupon plus metfmin $0 (non-medicare) Plus SGLT2i - $0-5/month coupon (non-medicare) No need f self-blood glucose moniting strips No need f titrations, frequent office visits, labaty testing, staff time f training, telephone calls, etc Innovation When Avoidance of Hypoglycemia Is the Priity Monotherapy Efficacy * Hypo risk Weight Side effects Costs Dual therapy Efficacy * Hypo risk Weight Side effects Costs Healthy eating, weight control, increased physical activity & diabetes education Metfmin neutral/loss GI / lactic acidosis If HbA1c target not achieved after ~3 months of monotherapy, proceed to 2-drug combination (der not meant to denote any specific preference - choice dependent on a variety of patient- & disease-specific facts): Metfmin Sulfonylurea moderate risk Metfmin Thiazolidinedione edema, HF, fxs Metfmin DPP-4 inhibit intermediate neutral rare Metfmin SGLT2 inhibit intermediate loss GU, dehydration Metfmin GLP-1 recept agonist loss GI Metfmin Insulin (basal) est risk variable Glycemic Control Algithm Triple therapy Metfmin Sulfonylurea If HbA1c target not achieved after ~3 months of dual therapy, proceed to 3-drug combination (der not meant to denote any specific preference - choice dependent on a variety of patient- & disease-specific facts): Metfmin Thiazolidinedione Metfmin DPP-4 Inhibit SGLT-2 Inhibit Metfmin Metfmin GLP-1 recept agonist Metfmin Insulin (basal) GLP-1-RA GLP-1-RA GLP-1-RA If HbA1c target not achieved after ~3 months of triple therapy and patient (1) on al combination, move to injectables, (2) on GLP-1 RA, add basal insulin, (3) on optimally titrated basal insulin, add GLP-1-RA mealtime insulin. In refracty patients consider adding SGL T2-i: Metfmin Figure 2A. An hyperglycemic Combination therapy injectable in T2DM: Basal Insulin Mealtime Insulin GLP-1-RA Avoidance therapy of Inzucchi SE, et al. Diabetes Care. 2015;38: ; 2015;38: Qiu Diabetologia F, al. Eye 2015; /s (Lond). 2014;28(4): AGi = alpha-glucosidase inhibit; /GLN = sulfonylurea/meglitinide. Garber AJ, et al. Endocr Pract. 2016;22(1):

10 Monotherapy Efficacy * Hypo risk Weight Side effects Costs Healthy eating, weight control, increased physical activity & diabetes education Metfmin neutral/loss GI / lactic acidosis Innovation When Weight Loss Is the Priity Dual therapy Triple therapy Efficacy * Hypo risk Weight Side effects Costs If HbA1c target not achieved after ~3 months of monotherapy, proceed to 2-drug combination (der not meant to denote any specific preference - choice dependent on a variety of patient- & disease-specific facts): Metfmin Sulfonylurea moderate risk Metfmin Sulfonylurea Metfmin Thiazolidinedione edema, HF, fxs Metfmin Thiazolidinedione Metfmin DPP-4 inhibit intermediate neutral rare Metfmin DPP-4 Inhibit Metfmin SGLT2 inhibit intermediate loss GU, dehydration SGLT-2 Inhibit Metfmin Metfmin GLP-1 recept agonist loss GI If HbA1c target not achieved after ~3 months of dual therapy, proceed to 3-drug combination (der not meant to denote any specific preference - choice dependent on a variety of patient- & disease-specific facts): Metfmin GLP-1 recept agonist Metfmin Insulin (basal) est risk variable Metfmin Insulin (basal) GLP-1-RA GLP-1-RA GLP-1-RA If HbA1c target not achieved after ~3 months of triple therapy and patient (1) on al combination, move to injectables, (2) on GLP-1 RA, add basal insulin, (3) on optimally titrated basal insulin, add GLP-1-RA mealtime insulin. In refracty patients consider adding SGL T2-i: Metfmin Figure 2B. An hyperglycemic Combination therapy injectable in T2DM: Basal Insulin Mealtime Insulin GLP-1-RA Avoidance therapy of weight Inzucchi SE, et al. Diabetes Care. 2015;38: ;38: ; Qiu Diabetologia F, al. Eye 2015; /s (Lond). 2014;28(4): Reduce Complications through Goal Achievement A Controversial and Confusing Subject Reach LDL Goals to Reduce Complications American Heart Association Guideline suggests 50% reduction with no goal American Diabetes Association agrees National Lipid Association has goals and American Association of Clinical Endocrinologists agrees IMPROVE-IT study demonstrated a reduction in CV outcomes adding ezetimibe to a statin (LDL ) Trials with PCSK9 inhibits added to a statin producing trends toward a decrease in events (LDL ) Cholesterol Treatment Trialists Collabation metaanalysis suggests that LDL <50 mg/dl leads to regression in plaque IMPROVE IT = Improved Reduction of Outcomes: Vytin Efficacy International Trial; PCSK9 = proprotein convertase subtilisin-kexin type 9. Cannon CT, et al. N Engl J Med. 2015;372: Sabatine M, et al. N Engl J Med. 2015;372: Baigent C. Lancet. 2010;376: Reach BP Goals to Reduce Complications American Diabetes Association goal of <140/90 but in some cases 130/80 American Association of Clinical Endocrinologists goal approximately 130/80 Systolic Blood Pressure Intervention Trial (SPRINT) (large multicenter trial) demonstrated 33% reduction in cardiovascular events at a target systolic BP of 120 but no patients with diabetes mellitus were included in the trial So where does that lead us? My opinion is American Diabetes Association. Diabetes Care. 2016;39(Suppl 1) S60-S71. Garber AJ, et al. Endocr Pract. 2016;22(1): SPRINT Research Group, et al. N Engl J Med. 2015;373:

11 Innovation f Cardiovascular Outcome Improvement: A New Era The Cardiovascular Outcome Improvement Era Last year, we had no drugs f diabetes mellitus with a proven cardiovascular disease outcome benefit Now we have three: EMPA-REG outcomes trial: Empagliflozin LEADER trial: Liraglutide IRIS trial: Pioglitazone Empagliflozin vs Placebo: All-Cause Mtality HR 0.68 (95% CI 0.57, 0.82) p< HR = hazard ratio. Zinman B et al. N Engl J Med. 2015;373(22): Empagliflozin Modulates Several Facts Related to CV Risk BP Arterial stiffness Other Albuminuria Number Needed to Treat to Prevent 1 Death across Landmark Trials in Patients with High CV Risk Simvastatin f 5.4 years Ramipril f 5 years Empagliflozin f 3 years Sympathetic nervous system activity Weight Visceral adiposity Glucose Insulin Oxidative stress Uric acid LDL-C HDL-C Triglycerides High CV risk 5% diabetes, 26% hypertension Pre-statin era High CV risk 38% diabetes, 46% hypertension Pre-ACEi/ARB era <29% statin T2DM with CV risk 92% hypertension >80% ACEi/ARB >75% statin Adapted from Inzucchi SE, et al. Diab Vasc Dis Res. 2015;12: S investigat. Lancet. 1994;344: HOPE investigat. N Engl J Med. 2000;342:

12 What Effect Will These Results Have on Clinical Practice Guidelines? The Wave of Innovation Is to Continue to Simplify Life with Diabetes Mellitus 67 GLP-1s Ready-to-Use Pen Characteristics Current Exenatide twice daily with meals Liraglutide once daily anytime Exenatide once weekly Dulaglutide once weekly Albiglutide once weekly Future Once monthly Once yearly Oral Steps f use: uncap, place, and unlock, inject Small, hidden needle Automatically retracts needle foling injection Provides dose confirmation delivery (5-10 seconds) GLP-1 = glucagon-like peptide 1. Ultra-Fine Needles and Syringes Pens Convenient Discreet Protect insulin from light/heat 12

13 Hol microneedles Needles Perpendicular 1-mm injection into the intradermal space (as opposed to subcutaneous) Me rapid uptake Reduce pain, anxiety, and fear of injections Ultra-fine and ultra-beveled needles - 33-gauge - Steeper angle in bevel to minimize pain at injection site Nman J, et al. Pediatr Diabetes. 2013;14(6): ; McVey E. J Diabetes Sci Technol. 2012;6(4); Novel Delivery Technologies Osmotic mini-pump: Size of small matchstick - Mini-pump provides continuous smooth zero der delivery of drugs Peptide stabilizing suspension als f robust stability at body temps and delivery of peptides f 12 months from just a single device Mini-pump is placed subdermally once/twice yearly in a sht in-office sterile procedure Procedures are done by specialists, primary care physicians, and nurse/physician assistants; there are already approved reimbursement codes Actual Size: 4 mm x 44 mm Semipermeable Osmotic Membrane Osmotic Engine Piston Drug Reservoir with Novel High Temp Peptide Stabilizing Suspension Diffusion Moderat Immediate-Release Exenatide What s the Take Home? Create planned visits f your patients with diabetes mellitus Eliminate the wd non-compliant Understand ientation and values of primary care clinicians Use registries to provide patient specific and population based repts as the foundation of team based care Reduce complications through goal achievement Take-Home Messages: Relationship with Your Patient Transfm your relationship with your patients and their families by recognizing you are a team, suppting lifestyle optimization, but focus on prescribing the best Rx regimen when appropriate Expect to devise an individualized Rx regimen: simple, affdable, safe, effective, easy to adhere to, minimal intrusion in daily life based on individual needs (eg, cost, hypos, weight) Individualize care by using a consistent, positive psychology, empowering patients to achieve control Eliminate the wd non-compliant Setbacks are never failures; they are problem-solving opptunities, but know that some patients need guilt, structure, etc Take-Home Messages: The Innovation Focus Assume multiple medications are required not a barrier failure Choose regimen based on individual patient needs Avoid diabeticizing : moniting, carb counting, visits, etc Basal insulin is a good option cost-effective Prandial insulin is the toughest option last rest Get control ASAP this helps treatment wk better with fewer agents Avoid overtreating the elderly and the sick The future of diabetes innovation is all about making it easier Questions? 13