Keep Calm and Focus on the Evidence for the Management of Diabetes. Diabetes Update PDF Free Download

Keep Calm and Focus on the Evidence for the Management of Diabetes Diabetes Update 2018 Nicole C.Pezzino, PharmD, BCACP, CDE Assistant Professor, Wilkes University Pharmacist, Weis Markets Nicole.pezzino@wilkes.edu

Disclosures Nicole C. Pezzino declare no conflicts of interest, real or apparent, and no financial interests in any company, product, or service mentioned in this program, including grants, employment, gifts, stock holdings, and honoraria.

Objectives Describe the evidence from clinical trials and noteworthy changes to the diabetes guidelines Evaluate patient cases to determine appropriate treatment options that focus on evidence-based recommendations Develop a individualized plan for implementation and follow-up for the patient

Who s in the room? Community Pharmacists? Ambulatory Care Pharmacists? Technicians? Hospital Pharmacists? Managed Care Pharmacists? Other?

How often do you interact with patients who have diabetes? Never Infrequently (1-4 times/month) Sometimes (5-10 times/month) Often (at least daily) Always (multiple times/ day)

Patient Case A patient presents to your community pharmacy diabetes clinic (you have a CPA for diabetes medications) with prescriptions for: 1. Metformin 850 mg by mouth once daily (#30; 5 RF) 2. Glipizide 10 mg by mouth once daily (#30; 5 RF) 3. Lantus 10 units subcutaneously at bedtime (#QS; 5 RF) 4. Alendronate 70 mg by mouth once weekly (#4; 5 RF) 5. Amlodipine 10 mg by mouth once daily (#30; 5 RF) 6. Hydrochlorothiazide 25 mg by mouth once daily (#30; 5 RF) She is a new patient to your pharmacy!

DOB: 1/27/1950 (68-years-old) Allergies: Sulfa drugs (hives) PMH: diabetes (10 years), hypertension (6 years), osteoarthritis (2 years) SHx: former smoker (30 PY; quit 10 years ago), denies alcohol and illicit drug use Relevant Labs (obtained 1/20/18): Glu: 208 mg/dl A1c: 8.9% K+: 4.2 meq/l BUN: 18 mg/dl Creatinine: 0.9 mg/dl creatinine, random urine: 310 mg/ dl Total Cholesterol: 188 mg/dl HDL: 29 mg/dl LDL: 123 mg/dl TG: 182 mg/dl

Nonprescription drugs: Aspirin 81 mg by mouth twice daily Cinnamon 1000 mg by mouth twice daily Fish Oil 1200 mg by mouth twice daily Calcium D-Glucarate 500 mg by mouth twice daily Vitamin D 2,000 units by mouth once daily (with breakfast) Melatonin 10 mg by mouth if needed for sleep Blood pressure: 148/92 mmhg (R arm, resting x10 minutes) Never graduated High School; SAHM Insurance: Geisinger Gold Standard Rx (Part D)

2018 Updates: American Diabetes Association

2018 by American Diabetes Association American Diabetes Association Dia Care 2018;41:S28-S37

2018 by American Diabetes Association American Diabetes Association Dia Care 2018;41:S73-S85

Technology General Update Resources added to various sections regarding the use of technology BeatO Log BG readings Diabetes Education Diabetes in Check Log BG + Meds & reminders Nutrition resources CDE Coaching Glooko Syncs to glucose meters Create charts MyFitnessPal Lifestyle app Log food & track nutrition facts

Section 1 Improving Care and Promoting Health in Populations Food insecurity Social Determinants of Health Housing stability Financial barriers Apply information to treatment decisions & refer to local community resources when available

Section 2 Classification and Diagnosis of Diabetes A1C limitations: Hemoglobin variants Assay interference Conditions with RBC turnover Utilize A1C test certified by NGSP and standardized to the Diabetes Control and Complications Trial (DCCT) Community screenings?

Section 9 Cardiovascular Disease and Risk Management Home BP monitoring Antihypertensive treatment approach Statin Use and Lipid management Agents that reduce cardiovascular events and/or mortality CVOT data on new diabetes agents + CVOT studies

Cardiovascular Outcomes Trials (CVOT)

DPP IV Inhibitor Cardiovascular Outcomes Trials SAVOR-TIMI 53 Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus (SAVOR) Thrombolysis in Myocardial Infarction (TIMI) EXAMINE The Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care in Patients with Diabetes TECOS Trial Evaluating Cardiovascular Outcomes with Sitagliptin

DPP IV Inhibitor Cardiovascular Outcomes Trials Trial Intervention; Number Diabetes duration; Median Follow-up Drug vs. Placebo (% Primary Endpoint) HR (95% CI) P value SAVOR- TIMI Saxagliptin/pl acebo N=16,492 10.3 yrs; 2.1 yrs 7.3 vs. 72 3-point MACE HR 1.00 (0.89-1.12); P<0.001 NI P=0.99 Not Superior EXAMINE Alogliptin/pla cebo N=5,380 7.1 yrs; 1.5 yrs 11.3 vs. 11.8 3- point MACE HR 0.96 (95% UL < CI 1.16); P<0.001 NI P=0.32 Not Superior TECOS Sitagliptin/pla cebo N=14,671 11.6 yrs; 3.0 yrs 11.4 vs. 11.6 4-point MACE HR 0.98 (0.89-1.08); P<0.001 NI P=0.65 Not Superior MACE: DPP-IV Inhibitors are noninferior to placebo; no superiority

GLP-1 RA Cardiovascular Outcomes Trials ELIXA Evaluation of Lixisenatide in Acute Coronary Syndrome LEADER Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcomes Results SUSTAIN-6 Trial to Evaluate Cardiovascular and Other Long-Term Outcomes with Semaglutide in Subjects with Type 2 Diabetes EXSCEL Exenatide Study of Cardiovascular Event Lowering

GLP-1 RA Cardiovascular Outcomes Trials Trial Intervention; Number Diabetes duration; Median F/U Drug vs. Placebo (% Primary Endpoint) HR (95% CI) P value ELIXA lixisenatide/plac ebo N=6,068 9.3 yrs; 2.1 yrs 13.4 vs. 13.2 4-point MACE ITT HR 1.02 (0.89-1.17) P<0.001 NI P=0.81 Not Superior LEADER liraglutide/place bo N=9,340 12.8 yrs; 3.8 yrs 13.0 vs. 14.9 ITT HR 0.87 (0.78-0.97) P<0.001 NI P=0.01 Superiority SUSTAIN-6 semaglutide/pla cebo N=3,297 13.9 yrs; 2.1 yrs 6.6 vs. 8.9 HR 0.74 (0.58-0.95) P<0.001 NI P=0.02 Superiority EXSCEL exenatide/place bo N=14,752 12 yrs; 3.2 yrs 11.4 vs. 12.2 ITT HR 0.91 (0.83-1.00) P<0.001 NI P=0.06 Not Superior

SGLT-2 Inhibitor Cardiovascular Outcomes Trials EMPA-REG: Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes CANVAS, CANVAS-R: Canagliflozin Cardiovascular Assessment Study, Canagliflozin and Renal Events in Type 2 Diabetes

SGLT-2 Inhibitor Cardiovascular Outcomes Trials Trial Intervention; Number Diabetes duration; Median Follow-up Drug vs. Placebo (% Primary Endpoint) HR (95% CI) P value EMPA-REG empagliflozin /placebo N=7,020 57% >10 yrs 3.1 yrs 10.5% vs. 12.1% 3-point MACE HR 0.86 (0.74-0.99) P<0.001 NI P=0.04 Superiority CANVAS/CA NVAS-R canagliflozin/ placebo N=4,330 N=5,812 13.5 yrs 5.7 yrs 2.1 yrs 9.8% vs. 10.1% 3- point MACE 89.4 vs. 128.7 (no. participants/1000 pt-yr) Progression to albuminuria HR 0.86 (0.75-0.97) P<0.001 NI P=0.02 Superiority HR 0.73 (0.47=0.77) P=not stated

DEVOTE Insulin Cardiovascular Outcomes Trials Trial Comparing Cardiovascular Safety of Insulin Degludec versus Insulin Glargine in Patients with Type 2 Diabetes at High Risk of Cardiovascular Events Trial Intervention; Number Diabetes duration; Median Follow-up Drug vs. Placebo (% Primary Endpoint) HR (95% CI) P value DEVOTE Degludec/gla rgine N=7,637 57% >10 yrs 3.1 yrs 8.5% vs. 9.3% (CV death, nonfatal MI/Stroke) HR 0.91 (0.78-1.06) P<0.0001 NI P=0.21 (Not Significant)

Which class would you recommend to be added to metformin? A. DPP-IV Inhibitor B. GLP-1 Analog C. SGLT-2 Inhibitor

Which of the following received the FDA expanded indication for CV safety in T2DM? A. Lixisenatide and linagliptin B. Exenatide and semaglutide C. Dapagliflozin and canagliflozin D. Liraglutide and empagliflozin

Summary Decrease CVD Risk No effect on CVD Risk

Individualized Diabetes Plans

Type 2 Diabetes Mellitus Secretagogues Sulfonylureas Acetohexamide Chlorpropamide Glimepiride* Glipizide* Glyburide* Tolazamide Tolbutamide Meglitinides Nateglinide Repaglinide Pharmacologic Treatment Oral Agents Antihyperglycemics Biguanides Metformin Thiazolidinediones Pioglitazone Roziglitazone α-glucosidase inhibitors Acarbose Miglitol DPP-4 inhibitors Sitagliptin Linagliptin Saxagliptin Alogliptin Injectable Agents Amylinomimetics Amylin analog Pramlintide Incretin Mimetics GLP-1 receptor agonist Exenatide (Immediate & Extended-Release) Liraglutide Albiglutide Dulaglutide Lixisenatide Semaglutide (approved Dec. 2017) Insulin Human Analog

Type 2 Diabetes Mellitus Pharmacologic Treatment Oral Agents Secretagogues Antihyperglycemics Bile Acid Sequestrants Colesevelam Dopamine Agonist Bromocriptine SGLT-2 Inhibitors Canagliflozin Dapagliflozin Empagliflozin Ertugliflozin* (coming January 2018)

Current Insulin Therapy Options Typ e Basal Insulin Prandial Insulin Premixed Insulin Human NPH U100 Regular human insulin U100 Regular human insulin U500 Insulin inhalation powder Analog Glargine U100 follow-on glargine U100 Glargine U300 Detemir U100 Degludec U100 Degludec U200 Lispro U100 Lispro U200 Aspart U100 Glulisine U100 Ultra rapid acting aspart (FIAsp) Regular human insulin 70/30 Lispro protamine + lispro 75/25 Lispro protamine + lispro 50/50 Aspart protamine + aspart 70/30 Insulin degludec + insulin aspart 70/30 Updated January 2018

Diabetes Medications and Their Effect on Blood Glucose Medication Alpha-glucosidase inhibitors Amylinomimetic (pramlintide) Biguanides (metformin) Bile Acid Sequestrants Dopamine agonists DPP-4 inhibitors GLP-1 agonists Meglitinides SGLT -2 Inhibitors Sulfonylureas TZDs Insulin (Basal) Insulin (Bolus) Effect on blood glucose Postprandial Postprandial Fasting Postprandial Postprandial Postprandial Short acting Postprandial Long acting Fasting and Postprandial Postprandial Fasting and Postprandial Fasting and Postprandial Fasting and Postprandial Fasting Postprandial Burke S, et al. Clinician Reviews. 2008;18:28-34.

Pharmacotherapy Options Islet b-cell Impaired Insulin Secretion Islet a-cell DPP4 Inhibitors GLP-1 Agonists Insulin Meglitinides Sulfonylureas Amylinomimetics DPP4 Inhibitors GLP-1 Agonists AGI Amylinomimetics Bile Acid Sequestrants GLP-1 Agonists Dietary Decreased Incretin Effect Increased Glucagon Secretion Increased HGP Neurotransmitter Dysfunction Amylinomimetics Biguanides DPP4 Inhibitors GLP-1 Agonists TZD s Amylinomimetics Dopamine Agonists GLP-1 Agonists Biguanide Insulin TZD s Biguanide Insulin TZD s SGLT-2 Inh Increased Lipolysis Decreased Glucose Uptake Increased Glucose Reabsorption

Patient Case 1

What are you taking your medications for? My physician prescribes the prescription ones for my diabetes, high blood pressure and arthritis. I don t have any complaints about them.. I ve been taking them for a while now. I take my aspirin because I had a heart attack 5 years ago and I think the calcium goes with my arthritis medicines. I also see a chiropractor for my back pain and to help my joints, and he recommended most of my supplements I am taking.

Assessment 68 year-old female with uncontrolled Type 2 Diabetes Mellitus using metformin 850 mg, glipizide 10 mg and basal insulin to manage her diabetes Requires medication optimization and lifestyle modifications Financial considerations with her Medicare Plan

Assessment Does she require other medication interventions to meet the ADA 2018 Standards of Care? If she does, what other medication interventions is she a candidate for? ACEi/ARB microalbuminuria + BP Metformin dose Statin therapy clinical ASCVD Aspirin dose https://www.aafp.org/afp/2014/0215/p256.html

Assessment Does she require any other non-medication related interventions to meet the ADA 2018 Standards of Care? If she does, what? Immunizations PCV13 PPSV23 (at least 5 years after previous PPSV23 dose) Annual influenza Hepatitis B 3 dose series (?) Medical Nutrition Therapy Referrals? Lab work?

Assessment What social determinants of health should we take into consideration with this patient case? Food insecurity Transportation Health Literacy Housing? Finances

Plan (Drug Therapy) Diabetes Nonprescription: Decrease Aspirin to once daily D/C Cinnamon and Fish Oil? Prescription: Metformin: increase dose to 2,000 mg daily D/C Glipizide (?) Plan to increase Lantus (insulin glargine) dose OR consider Xultophy (insulin degludec and liraglutide) Add empagliflozin vs. liraglutide?

Plan (Standards of Care) Optimize: Lifestyle: exercise + diet Candidate for high-intensity statin Albuminuria: initiate ACEi/ARB Vaccinations: PCV13 + PPSV23, Influenza, Hepatitis B(?) Confirm Appointments: Lab work? Follow-up appointments

Patient s Plan Goals of Therapy: Reduce the risk of cardiovascular events and keep blood glucose at/near normal levels Manage drug therapy to reduce the risk of adverse events Goals: A1C Goal: ADA 2018 - <7% BG Goals: FBG 80-130 mg/dl; PPG <180 mg/dl BP Goal: <140/90 mmhg Cholesterol Goal: appropriate statin therapy

Patient s Plan Drug Therapy: Could consider: Initiate Xultophy 100/3.6 (insulin degludec and liraglutide) titrated to 50 units Discontinue lantus + glipizide Increase metformin to 1,000 mg twice daily D/C Hydrochlorothiazide 25 mg and initiate Lisinopril 10 mg/hydrochorothiazide 25 mg Initiate atorvastatin 40-80 mg Vaccines: Obtain patient s charts

Implementing the Plan (Education) Diet Reduce: saturated fat, trans fat and cholesterol intake Increase: dietary n-3 fatty acids, viscous fiber, plant stanols/sterols Physical Activity Low-impact, weight bearing exercise 150 minutes of aerobic activity Diabetes (in general) SMBG home monitoring Technology use??

Monitoring Xultophy Counseling on nausea & how to reduce Pen and needle use (rotate injection site no sharing, disposal) Hypoglycemia counseling Educate on goals and titrating dose Lisinopril/Hydrocholorthiazide: Home blood pressure monitoring Educate on goals Atorvastatin: Timing, side effect potential Follow-up lab work?

Evaluate & Monitor Short-term (1 to 3 months) Adverse events Adherence Follow-up appointment with physician (3 months) + a1c Confirm referrals Intermediate-term (3 to 12 months) Adherence to medication therapy Weight loss goals? Determine follow-up plan Long-term (12+ months) Follow-up lab work Confirm all interdisciplinary appointments

Key Points ADA 2018 Guidelines focus on individualization and evidencedbased recommendations including incorporation of medications with known cardiovascular benefit and the use of technology in diabetes management Empagliflozin and liraglutide received FDA approval for reduction of cardiovascular risk in patients with type 2 diabetes and preexisting heart disease Heart failure with DPP-IV inhibitors doesn t appear to be a class effect

Keep Calm and Focus on the Evidence for the Management of Diabetes. Diabetes Update 2018