Presented By: Creative Educational Concepts, Inc. Lexington, KY

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2 Disclaimer This slide deck in its original and unaltered format is for educational purposes and is current as of April The content and views presented in this educational activity are those of the authors/presenters and do not necessarily reflect those of Creative Educational Concepts or the supporter. These materials may discuss therapeutic products that have not been approved by the US Food and Drug Administration and offlabel uses of approved products. A qualified healthcare professional should be consulted before using any therapeutic product discussed. Readers should verify all information and data before treating patients or employing any therapies or strategies described in this educational activity.

3 Usage Rights This slide deck is provided for educational purposes and slides may be used for personal, non-commercial presentations only as long as content and references remain the same. No part of this slide deck may be published or distributed in print or electronic format without prior written permission from Creative Educational Concepts.

4 Presented By: Creative Educational Concepts, Inc. Lexington, KY

5 Special Thanks! Supported through an independent educational grant from: AstraZeneca

6 Navigating the Guidelines: Updates in Antihyperglycemic Therapies and ADA/EASD and AACE Guidelines in 2015 Stuart T. Haines, PharmD, BCPS, BCACP, BC-ADM Professor and Vice Chair for Clinical Services University of Maryland School of Pharmacy Baltimore, MD

7 Case Study DR is a 62-year-old African American female presenting to the Medication Therapy Management Clinic for a medication review Chief Complaint: I have diabetes, and my blood glucose isn t doing so well Past Medical History: Type 2 Diabetes Mellitus (T2DM), Hypertension, Dyslipidemia, Obesity, Carpal Tunnel Syndrome

8 Case Study (cont.) Medications Aspirin 81 mg orally daily Amlodipine 5 mg orally daily Lisinopril 10 mg orally daily Atorvastatin 20 mg orally daily Calcium + Vitamin D supplement 1 tablet orally twice daily Ibuprofen as needed for headaches and joint pain

9 Case Study (cont.) Social History Comprehensive health plan through work Prescription drug plan 3 tiers ($10/$25/40%) High school teacher (hoping to retire soon) Drinks socially (2-3/month) Does use tobacco products/smoke Lives with husband; grown children and grandchild live nearby

10 Case Study (cont.) Subjective Data Nocturia 1-2 times per night; denies excessive thirst or weight loss Physical Exam BP=142/78 mmhg Pulse=88 bpm, regular Weight=230 lbs Height=65 BMI=38.3 kg/m 2

11 Case Study (cont.) Laboratory Tests (1 week ago) Na=141 meq/l K=4.6 meq/l BUN=14 mg/dl SCr=1.1 mg/dl Glucose=157 mg/dl A1C=8.7% AST=34 units/l ALT=26 units/l Total Cholesterol=151 mg/dl (LDL=87 mg/dl; HDL=34 mg/dl; TG=178 mg/dl)

12 Pathophysiology of Diabetes Impaired GI motility and incretin effect GI Tract Defective -cell function Pancreas Diminished or absent insulin and amylin release Brain Insulin resistance Reduced glucose uptake Muscle Liver Excess glucose production Scheen AJ. Acta Clin Belg. 2003; DeFronzo RA, et al. Diabetes Care

13 Treatment Approach to T2DM Dietary changes Reduce consumption of calories Reduce consumption of simple carbohydrates Increase physical activity Medications Improve insulin secretion Mitigate insulin resistance Reduce hepatic glucose production Increase urinary glucose excretion DeFronzo RA, et al. Diabetes Care

14 Treatment Options T2DM Medications Approved before 2000 Exogenous insulin (human and analogs) Sulfonylureas Biguanides (metformin) Alpha-glucosidase inhibitors (AGIs) Meglitinides Thiazolidinediones (TZDs) Stein SA, et al. Expert Opin Drug Saf. 2013; Fowler MJ. Clin Diabetes

15 Treatment Options T2DM Medications Approved since 2005! Amylin analogues (pramlintide) Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) Dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitors) Bile acid sequestrant (colesevelam) Dopamine agonist (bromocriptine) Sodium-glucose cotransporter 2 inhibitors (SGLT-2 inhibitors) Stein SA, et al. Expert Opin Drug Saf. 2013; Fowler MJ. Clin Diabetes

16 ADA Standards of Medical Care in Diabetes (2015) METFORMIN American Diabetes Association. Diabetes Care

17 ADA Standards of Medical Care in Diabetes (2015) Dual and Triple Therapy METFORMIN Sulfonylurea Thiazolidinedione DPP-4 Inhibitor SGLT2 Inhibitor GLP-1 RA Basal Insulin In 2 or 3 drug combinations American Diabetes Association. Diabetes Care

18 ADA Standards of Medical Care in Diabetes (2015) Injectable Therapy METFORMIN Basal Insulin Prandial Insulin OR GLP-1 RA American Diabetes Association. Diabetes Care

19 AACE Glycemic Control Algorithm (2013) Garber AJ, et al. Endocr Pract

20 AACE Glycemic Control Algorithm (2013) Preferred 1 st line agents Metformin (use unless contraindicated) DPP-4 Inhibitors GLP-1 RAs AGIs Preferred add-on agents Colesevelam Bromocriptine Garber AJ, et al. Endocr Pract

21 Metformin Cornerstone of Therapy Affordable Positive/neutral impact on weight Low risk of hypoglycemia GI side effects can be managed Risk of lactic acidosis far less than feared Effectively lowers blood glucose and A1C alone or in combination with other treatments Reduces risk of diabetes complications Inzucchi SE, et al. JAMA. 2014; UK Prospective Diabetes Study (UKPDS) Group. Lancet

22 My Ideal Add-On Agent Effective gets to goal BG and A1C Well tolerated and safe Addresses multiple metabolic abnormalities Promotes weight loss Durable glycemic effect Reduces risk of diabetes-related complications and death Oral, once daily, and inexpensive

23 Practical Applications for the Appropriate Use of GLP-1 Receptor Agonists to Optimize Glycemic Control Dawn Fuke, PharmD, BCPS Primary Care Clinical Pharmacy Specialist Clinical Pharmacy Providence Medical Group Portland, OR

24 Notes

25 GLP-1 Receptor Agonists GLP-1: incretin secreted by intestinal L cells GLP-1 receptors Satiety Appetite Slows gastric emptying Insulin release Glucagon release Donnelly D. Br J Pharmacol

26 GLP-1 Receptor Agonists (cont.) Exenatide 5-10 mcg twice daily (Byetta 2005) 2 mg once weekly (Bydureon 2012) Liraglutide mg daily (Victoza 2010) 3 mg daily (weight loss indication, Saxenda 2014) Albiglutide mg once weekly (Tanzeum 2014) Dulaglutide mg once weekly (Trulicity 2014) Lixisenatide (anticipated FDA submission 2015)

27 GLP-1 RAs: Exenatide: 2 trials (N=1,156) Liraglutide: 1 trial (N=746) Dulaglutide: 1 trial (N=807) Albiglutide: no monotherapy trials Monotherapy 4 studies: GLP-1 RAs vs. placebo or active control Active control: Glimepiride 8 mg/day Metformin 1,500-2,000 mg/day Pioglitazone 45 mg/day Sitagliptin 100 mg/day weeks Moretto TJ, et al. Clin Ther. 2008; Russell-Jones D, et al. Diabetes Care. 2012; Garber A, et al. Lancet. 2009; Umpierrez G, et al. Diabetes Care

28 Exenatide Monotherapy: Results Dose A1C (%) 5-10 mcg twice daily to -0.9 FPG (mg/dl) to PPG (mg/dl) to Weight (kg) -2.8 to Placebo Exenatide 2 mg/week N/A -2.0 Metformin 2,000 mg/day N/A -2.0 Pioglitazone 45 mg/day N/A 1.5 Sitagliptin 100 mg/day N/A -0.8 Exenatide twice daily: more effective in glycemic control and weight loss compared to placebo Exenatide once weekly Glycemic control: as effective as metformin; more effective than sitagliptin; not noninferior to pioglitazone Weight loss: more effective than sitagliptin and pioglitazone; similar to metformin FPG=Fasting Plasma Glucose; PPG=Postprandial Glucose Moretto TJ, et al. Clin Ther. 2008; Russell-Jones D, et al. Diabetes Care

29 Monotherapy: Results Dose A1C (%) FPG (mg/dl) Liraglutide mg/day -1.0 to to -26 PPG (mg/dl) to Weight (kg) -2.1 to -2.8 Glimepiride 8 mg/day Dulaglutide Metformin mg/week 1,500-2,000 mg/day to to to to to Liraglutide: more effective in glycemic control and weight loss compared to glimepiride Dulaglutide: as effective in glycemic control and weight loss as metformin Garber A, et al. Lancet. 2009; Umpierrez G, et al. Diabetes Care

30 GLP-1 Receptor Agonist Monotherapy Glycemic control: More effective than placebo, DPP-4 inhibitors and sulfonylureas As effective as metformin Not noninferior to TZD Weight loss: More effective than placebo, DPP-4 inhibitors, TZD and sulfonylureas As effective as metformin

31 Combination with Metformin 7 studies: metformin + GLP-1 RAs vs. metformin + placebo or active control GLP-1 RA: Exenatide: 2 trials (N=850) Liraglutide: 3 trials (N=2,351) Dulaglutide: 2 trials (N=1,697) Albiglutide: 1 trial (N=1,012) Active control: Glimepiride 2-4 mg/day Pioglitazone 45 mg/day Sitagliptin 100 mg/day weeks DeFronzo RA, et al. Diabetes Care. 2005; Bergenstal RM, et al. Lancet. 2010; Nauck M, et al. Diabetes Care. 2009; Pratley R. Int J Clin Pract. 2011; Nauck M, et al. Diabetes Care. 2014; Dungan KM, et al. Lancet. 2014; Ahrén B, et al. Diabetes Care

32 Exenatide Exenatide + Metformin Dose A1C (%) 5-10 mcg twice daily -0.4 to -0.8 FPG (mg/dl) -7.2 to PPG (mg/dl) Weight (kg) ~ to -2.8 Placebo ~ Exenatide 2 mg/week N/A -2.3 Pioglitazone 45 mg/day N/A 2.8 Sitagliptin 100 mg/day N/A -0.8 Metformin + Exenatide twice daily: more effective in glycemic control and weight loss compared to placebo Metformin + Exenatide once weekly: Glycemic control: More effective than pioglitazone (A1C) and sitagliptin (A1C and FPG) Weight loss: More effective than pioglitazone and sitagliptin DeFronzo RA, et al. Diabetes Care. 2005; Bergenstal RM, et al. Lancet

33 Liraglutide Liraglutide + Metformin Dose A1C (%) mg/day FPG (mg/dl) -1 to PPG (mg/dl) to Weight (kg) -2.6 to -3.6 Placebo Glimepiride 4 mg/day -0.4 to Liraglutide mg/day to to -37 N/A -2.8 to -3.6 Sitagliptin 100 mg/day N/A Metformin + Liraglutide Glycemic control: More effective than placebo and sitagliptin As effective as glimepiride Weight loss: More effective than placebo, glimepiride and sitagliptin Nauck M, et al. Diabetes Care. 2009; Pratley R, et al. Int J Clin Pract

34 Dulaglutide + Metformin Dose A1C (%) FPG (mg/dl) PPG (mg/dl) Dulaglutide mg/week to to -43 N/A Weight (kg) -2.6 to Placebo N/A -1.5 Sitagliptin 100 mg/day N/A Dulaglutide mg/week Liraglutide mg/day Metformin + Dulaglutide: Glycemic control: More effective than placebo and sitagliptin As effective as liraglutide Weight loss: More effective than placebo and sitagliptin Less effective than liraglutide Nauck M, et al. Diabetes Care. 2014; Dungan KM, et al. Lancet

35 Albiglutide + Metformin Dose A1C (%) FPG (mg/dl) PPG (mg/dl) Weight (kg) Albiglutide mg/week N/A Placebo N/A -1.0 Glimepiride 2-4 mg/day N/A 1.17 Sitagliptin 100 mg/day N/A Metformin + Albiglutide: Glycemic control: More effective than placebo, glimepiride and sitagliptin Weight loss: More effective than glimepiride Not significant compared to placebo or sitagliptin Nauck M, et al. Diabetes Care. 2014; Dungan KM, et al. Lancet

36 GLP-1 RAs with Metformin Glycemic control: More effective than placebo, TZD, and DPP-4 inhibitors As effective as sulfonylureas Liraglutide similar to dulaglutide Weight loss: More effective than placebo, sulfonylureas, TZD, and DPP-4 inhibitors Liraglutide more effective than dulaglutide

37 Triple Therapy 7 studies added GLP-1 RAs to metformin + an additional oral antidiabetic agent (N=4,369) Glycemic control: A1C reductions (-0.8 to -1.3%) More effective than placebo As effective as TZD and insulin Weight loss: -0.4 to -2.3 kg More effective than TZD or insulin Kendall DM, et al. Diabetes Care. 2005; Home PD, et al. Diabetes Obes Metab. 2015; Heine RJ, et al. Ann Intern Med. 2005; Russell-Jones D, et al. Diabetologia. 2009; Wysham C, et al. Diabetes Care. 2014; Zinman B, et al. Diabetes Care. 2009; Reusch J, et al. Diabetes Obes Metab

38 GLP-1 RAs vs. Insulin Glargine 4 randomized open-label trials (N=2,333) Exenatide twice daily, exenatide weekly, liraglutide or albiglutide No studies comparing dulaglutide Stable on oral diabetes medications Insulin glargine titrated to FPG <100 mg/dl HARMONY 4 (albiglutide): glargine 10 units/day weeks Heine RJ, et al. Ann Intern Med. 2005; Diamant M, et al. Lancet. 2010; Russell-Jones D, et al. Diabetologia. 2009; Weissman PN, et al. Diabetologia

39 GLP-1 RAs vs. Insulin Glargine Dose A1C (%) Glycemic control: Similar A1C reductions FPG reduction greater with insulin glargine PPG reduction greater with GLP-1 RAs Weight: GLP-1 RAs more effective FPG (mg/dl) PPG (mg/dl) Weight (kg) Exenatide 10 mcg twice daily Exenatide 2 mg/week Liraglutide 1.8 mg/day Albiglutide 30 mg/week N/A Insulin Glargine to to to to 1.8 Heine RJ, et al. Ann Intern Med. 2005; Diamant M, et al. Lancet. 2010; Russell-Jones D, et al. Diabetologia. 2009; Weissman PN, et al. Diabetologia

40 GLP-1 RA vs. Prandial Insulin HARMONY 6: albiglutide vs. insulin lispro Randomized, open-label trial (N=563) Insulin glargine + oral diabetes agents Metformin, pioglitazone, and/or AGIs Sulfonylureas, glinides, and DPP-4 inhibitors d/c 1 week prior to start Dose A1C (%) FPG (mg/dl) Glycemic control noninferior to lispro Weight change significant vs. lispro PPG (mg/dl) Weight (kg) Albiglutide 30 mg/week N/A -0.7 Insulin Lispro Prandial N/A 0.8 Rosenstock J, et al. Diabetes Care

41 Head to Head Comparisons 7 direct comparison trials (N=4,311) Randomized, open-label Noninferiority design Some superiority analyses in specific trials Various oral glucose lowering agent combinations weeks Buse JB, et al. Lancet. 2009; Buse J, et al. Lancet. 2013; Dungan KM, et al. Lancet. 2014; Pratley RA, et al. Lancet Diabetes Endocrinol. 2014; Drucker DJ, et al. Lancet. 2008; Blevins T, et al. J Clin Endocrinol Metab. 2011; Wysham C, et al. Diabetes Care

42 Exenatide Twice Daily: Head to Head 4 studies: exenatide twice daily (N=2,444) Dose A1C (%) FPG (mg/dl) PPG (mg/dl) Glycemic control: Less effective: exenatide weekly, liraglutide, dulaglutide Weight: Less effective: liraglutide, dulaglutide 1.5 mg dose Similar efficacy: exenatide weekly Weight (kg) Exenatide 10 mcg twice daily -0.8 to to to -3.6 Exenatide 2 mg/week -1.6 to to -41 N/A -2.3 to -3.7 Liraglutide 1.8 mg/day N/A Dulaglutide mg/week to to to to 0.2 Drucker DJ, et al. Lancet. 2008; Blevins T, et al. J Clin Endocrinol Metab. 2011; Buse J, et al. Lancet. 2013; Wysham C, et al. Diabetes Care

43 Liraglutide: Head to Head 4 studies: liraglutide (N=2,786) Dose A1C (%) FPG (mg/dl) Glycemic control: More effective: exenatide twice daily and weekly, albiglutide Noninferior: dulaglutide Weight: More effective: exenatide weekly, dulaglutide, albiglutide PPG (mg/dl) Weight (kg) Liraglutide 1.8 mg/day to to to to Exenatide 10 mcg twice daily Exenatide 2 mg/week N/A Dulaglutide 1.5 mg/week Albiglutide mg/week N/A Buse JB, et al. Lancet. 2009; Buse J, et al. Lancet. 2013; Dungan KM, et al. Lancet. 2014; Pratley RA, et al. Lancet Diabetes Endocrinol

44 Overall Efficacy Glycemic control: Monotherapy, combination with oral antidiabetic agents and basal insulin % reduction in baseline A1C Up to ~60 mg/dl decrease in FPG and PPG Weight: Up to 3.6 kg weight loss

45 Side Effects and Safety Side effects Nausea and gastrointestinal symptoms most common (up to 30%) Headache (up to 13%) Hypoglycemia (more common in combination therapy) Injection site reactions (more common with exenatide once weekly and albiglutide) Safety Acute pancreatitis/pancreatic cancer Medullary thyroid carcinoma FDA Prescribing Information.

46 Steering Patients through Medication Therapy Management: Case-Based Strategies to Improve Medication Use in Your Patients Nicholas Leon, PharmD, BCPS, BCACP Assistant Professor, Department of Pharmacy Practice Thomas Jefferson University Philadelphia, PA

47 Practical Considerations Is this the best type of medication for this patient? Is this an appropriate therapy for this patient? Is this the right therapy for this patient? Potential additional benefits Mitigating adverse effects Potential long term risks Will the patient have access to this medication? Cost issues Formulary considerations Will the patient be able to use this medication appropriately? Drug administration technique Initiating and titrating these drugs Monitoring therapy

48 Primary Benefits of GLP-1 Receptor Agonists Monotherapy or add on therapy for type 2 diabetes A1C by 1-1.7% Avoidance of hypoglycemia insulin secretion in a glucosedependent manner glucagon secretion similarly May need to dose of insulin or insulin secretagogue to reduce the risk of hypoglycemia Can be used with elevated PPG and FPG Mechanism really focuses in on PPG Avoidance of weight gain/ promotion of weight loss Promote a 1-4 kg weight loss in most Promotion of satiety appetite and food intake Pts appear to maintain weight loss while on therapy Nauck MA. Diabetes Care

49 Potential Additional Benefits Decrease in systolic blood pressure of 2-7 mmhg Improved endothelial function Enhanced natriuresis and fluid excretion Vasodilation Effect on triglycerides -12 to -40 mg/dl Nauck MA. Diabetes Care

50 GI Adverse Effects: Head to Head LEAD 6 N Mean Exposure Nausea % Diarrhea % Vomiting % # of pt withdrawals due to nausea Liraglutide 1.8 mg 235 Exenatide 10 mcg twice daily 26 weeks patients patients DURATION 6 N Mean Exposure Nausea % Diarrhea % Vomiting % # of pt withdrawals due to GI ADEs Liraglutide 1.8 mg 450 Exenatide 2 mg once weekly 26 weeks patients patients ADE=Adverse Drug Event Buse JB, et al. Lancet. 2009; Buse J, et al. Lancet

51 GI Adverse Effects: Head to Head AWARD 6 N Mean Exposure Nausea % Diarrhea % Vomiting % # of pt withdrawals due to GI ADEs Liraglutide 1.8 mg patients 26 weeks Dulaglutide 1.5 mg patients HARMONY 7 N Mean Exposure Nausea % Diarrhea % Vomiting % # of pt withdrawals due to GI ADEs Liraglutide 1.8 mg patients 32 weeks Albiglutide 50 mg patients Dungan KM, et al. Lancet. 2014; Pratley RA, et al. Lancet Diabetes Endocrinol

52 Mitigation of Common Adverse Effects Nausea Usually mild moderate Peaks within 4-10 weeks Resolves in all but ~10% of cases in a similar time frame Within 28 weeks with exenatide twice daily Hypoglycemia Depends on background therapy Mostly in combination with insulin and insulin secretagogues May need to decrease the dose of insulin or insulin secretagogue to reduce the risk of hypoglycemia Nauck MA. Diabetes Care

53 Injection Site Reactions LEAD 6 Skin and Subcutaneous Tissue Disorders General Disorders and Administration Site Conditions Liraglutide 1.8 mg 3.4% 8.9% Exenatide 10 mcg twice daily 6.9% 9.1% DURATION 6 Subcutaneous Nodule Injection Site Erythema Injection Site Pruritus Liraglutide 1.8 mg 0% <1% <1% Exenatide 2 mg once weekly 4% 2% 3% Buse JB, et al. Lancet. 2009; Buse J, et al. Lancet

54 Injection Site Reactions Liraglutide 1.8 mg Dulaglutide 1.5 mg AWARD 6 Injection-site reactions were uncommon in both groups. HARMONY 6 Injection Site Reaction Liraglutide 1.8 mg 5.4% Albiglutide 50 mg 12.9% Dungan KM, et al. Lancet. 2014; Rosenstock J, et al. Diabetes Care

55 Acute Pancreatitis Meta-analysis: BMJ RCTs; 14,562 patients Median 26 weeks Range total events in experimental group 0.11% event rate OR 1.05; 95% CI Li L, et al. BMJ

56 Medullary Thyroid Carcinoma (MTC): Black Box Warning Rodents C-cell lines are equipped with 22 to 45 fold more GLP-1 receptors than humans Pre-clinical studies showed proliferative changes in thyroid C cells Dose dependent increases of calcitonin in rodents given liraglutide Diabetes and Cancer an AACE/ACE Consensus Statement 2013 Exenatide twice daily 0.3 cases per 100 patient-years vs. zero cases per 100 patient-years for comparators Exenatide once weekly No cases of MTC were reported in Europe Liraglutide Calcitonin did not increase in liraglutide treated patients 1.3 cases per 1,000 patient-years vs. 1.0 cases per 1,000 patient-years Handelsman Y, et al. Endocr Pract

57 Risk Evaluation and Mitigation Strategies (REMS) For acute pancreatitis and the potential risk of medullary thyroid carcinoma Communication plan only Exenatide once weekly, liraglutide, dulaglutide, albiglutide No REMS Exenatide twice daily released from requirement 8/5/ PatientsandProviders/ucm htm.

58 Exenatide twice daily Exenatide once weekly Initiation and Titration Initial Dose 5 mcg for 1 month Treatment Dose Maximum Dose 10 mcg 10 mcg 2 mg Dose Adjustments CrCl <30 ml/min: Not recommended Comments Within 60 minutes prior to a meal Liraglutide daily Albiglutide once weekly Dulaglutide once weekly 0.6 mg for 1 week 30 mg 0.75 mg 1.2 mg 1.8 mg* 30 or 50 mg 0.75 or 1.5 mg 50 mg None None; Limited experience with renal impairment Missed dose, administer as soon as possible if within 3 days 1.5 mg None recommended *May need to decrease dose of insulin or insulin secretagogue to reduce the risk of hypoglycemia FDA Prescribing Information.

59 Exenatide Twice Daily and Liraglutide Administration Actual administration of dose is much like an insulin pen Available in prefilled syringes Store unused pens in refrigerator Store used pens at room temperature (up to 30 days after 1 st use) Need to attach 4, 5, or 6 mm pen needle Inject in subcutaneous tissue in abdomen, thigh or arm FDA Prescribing Information.

60 Exenatide Once Weekly Administration (Pen) Hold pen upright Assure liquid in inspection window is clear Attach needle Twist knob on bottom until you hear a click Green label should disappear Tap pen against palm of hand firmly Rotate every 10 taps May need to tap more than 80 times Look through inspection window to assure thoroughly mixed Should be uniformly cloudy Once mixed, twist knob again until you hear a click Orange label should disappear Injection button will appear from bottom Push injection button to administer dose FDA Prescribing Information.

61 Albiglutide Administration Viewing window should display the # 1 Twist until you hear a click see # 2 in viewing window Rock pen side to side gently 5 times do not shake Wait 30 minutes for medication to dissolve Rock pen side to side gently 5 times Viewing window should be clear Attach needle by pushing down hear click and feel snap Tap for air bubbles 2-3 times Twist pen to prime device see # 3 in viewing window Push injection button to administer FDA Prescribing Information.

62 Dulaglutide Administration (Pen) Needle comes already attached Remove base cap, hold to skin Turn indicator to the right unlocks pen Press green button hear click Hold pen in place for 5-10 seconds until second click is heard Throw device in sharps container FDA Prescribing Information.

63 Formulary Considerations Safety GI ADEs Injection site reactions are more common than with insulin Efficacy Lack of comparative trials with patient-important long-term outcomes Microvascular or macrovascular complications Health-related quality of life Mortality

64 Formulary Considerations Cost What the health plan assumes What the patient assumes Used before other oral therapies? Cost of other oral agents Cost of potential increased self-monitoring of blood glucose (SMBG) with insulin secretagogues Cost of hypoglycemia Used instead of insulin? Consider total cost Cost of insulin(s) Insulin pen needles Cost of increased SMBG with use of intermediate or rapid acting insulin Cost of hypoglycemia Ease of Use What about our patient DR???

65 Importance of Education

66