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This program is sponsored by and the speaker is presenting on behalf of Lilly USA, LLC. It is being presented consistent with FDA guidelines and is not approved for continuing education credit. In the Participant Guide, please see Important Safety Information, including Boxed Warning about possible thyroid tumors incl uding thyroid cancer, the Full Prescribing Information, and Medication Guide. 1 The goal of this program is to review information pertinent to the topic and answer your questions. For questions that directly relate to this topic and/or are consistent with product labeling, I will respond during the program. For all other questions, I will be glad to talk with you individually at the conclusion of the program. In the Participant Guide, please see Important Safety Information, including Boxed Warning about possible thyroid tumors incl uding thyroid cancer, the Full Prescribing Information, and Medication Guide. 2 WELCOME Trulicity: A case study in treating adult patients with type 2 diabetes DG96638 06/2015 ©Lilly USA, LLC 2015. All rights reserved. In the Participant Guide, please see Important Safety Information, including Boxed Warning about possible thyroid tumors incl uding thyroid cancer, the Full Prescribing Information, and Medication Guide. 3 Indication Trulicity™ (dulaglutide) is a glucagon-like peptide-1 receptor agonist (GLP-1 RA) that is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Limitations of Use • Not recommended as first-line therapy for patients inadequately controlled on diet and exercise because of the uncertain relevance of rodent C-cell tumor findings to humans. Prescribe only if potential benefits outweigh potential risks. • Has not been studied in patients with a history of pancreatitis. Consider other antidiabetic therapy. • Not for the treatment of type 1 diabetes mellitus or diabetic ketoacidosis. Not a substitute for insulin. • Has not been studied in patients with severe gastrointestinal disease, including severe gastroparesis. Not for patients with pre‐existing severe gastrointestinal disease. • Has not been studied in combination with basal insulin. Trulicity [Prescribing Information]. Indianapolis, IN: Lilly USA, LLC; 2015. In the Participant Guide, please see Important Safety Information, including Boxed Warning about possible thyroid tumors incl uding thyroid cancer, the Full Prescribing Information, and Medication Guide. 4 Important Safety Information—Boxed Warning WARNING: RISK OF THYROID C-CELL TUMORS In male and female rats, dulaglutide causes a dose-related and treatment-durationdependent increase in the incidence of thyroid C-cell tumors (adenomas and carcinomas) after lifetime exposure. It is unknown whether Trulicity causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans as human relevance of dulaglutide-induced rodent thyroid C-cell tumors has not been determined. Trulicity is contraindicated in patients with a personal or family history of MTC and in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). Counsel patients regarding the potential risk of MTC with use of Trulicity and inform them of symptoms of thyroid tumors (eg, mass in the neck, dysphagia, dyspnea, persistent hoarseness). Routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for early detection of MTC in patients treated with Trulicity. Trulicity [Prescribing Information]. Indianapolis, IN: Lilly USA, LLC; 2015. In the Participant Guide, please see Important Safety Information, including Boxed Warning about possible thyroid tumors incl uding thyroid cancer, the Full Prescribing Information, and Medication Guide. 5 Important Safety Information (continued) Trulicity is contraindicated in patients with a personal or family history of MTC or in patients with MEN 2, and in patients with a prior serious hypersensitivity reaction to dulaglutide or any of the product components. Risk of Thyroid C-cell Tumors: Cases of MTC in patients treated with liraglutide, another GLP-1 receptor agonist, have been reported in the postmarketing period; the data in these reports are insufficient to establish or exclude a causal relationship between MTC and GLP-1 RA use in humans. If serum calcitonin is measured and found to be elevated or thyroid nodules are noted on physical examination or neck imaging, the patient should be further evaluated. Pancreatitis: Has been reported in clinical trials. Observe patients for signs and symptoms including persistent severe abdominal pain. If pancreatitis is suspected, discontinue Trulicity promptly. Do not restart if pancreatitis is confirmed. Consider other antidiabetic therapies in patients with a history of pancreatitis. Hypoglycemia: The risk of hypoglycemia is increased when Trulicity is used in combination with insulin secretagogues (eg, sulfonylureas) or insulin. Patients may require a lower dose of the sulfonylurea or insulin to reduce the risk of hypoglycemia. Trulicity [Prescribing Information]. Indianapolis, IN: Lilly USA, LLC; 2015. In the Participant Guide, please see Important Safety Information, including Boxed Warning about possible thyroid tumors incl uding thyroid cancer, the Full Prescribing Information, and Medication Guide. 6 Pathogenesis of type 2 diabetes • The pathogenesis of diabetes is multifactorial • Insulin resistance in muscle and liver and β-cell failure represent the core pathophysiologic defects in type 2 diabetes • In addition to the fat cell, the GI tract, the α-cell, kidneys, and brain all play important roles in developing glucose intolerance Decreased insulin secretion Decreased incretin effect Increased lipolysis Hyperglycemia Islet α-cell Increased glucose reabsorption Increased glucagon secretion GI = gastrointestinal. Increased hepatic glucose production Neurotransmitter dysfunction Decreased glucose uptake Defronzo RA. Diabetes. 2009;58(4):773-795. In the Participant Guide, please see Important Safety Information, including Boxed Warning about possible thyroid tumors incl uding thyroid cancer, the Full Prescribing Information, and Medication Guide. 7 American Diabetes Association/EASD and AACE: Recommend reviewing treatment ~3 months Treatment guidelines recommend assessing patient progress in reaching goal approximately every 3 months and then1-3: Modify Maintain treatment when A1C goal not reached treatment when A1C goal is reached AACE = American Association of Clinical Endocrinologists. 1. Inzucchi SE, et al. Diabetes Care. 2012;35(6):1364-1379. 2. AACE/ACE Diabetes Guidelines, Endocr Pract. 2015;21(Suppl 1):1-87. 3. Inzucchi SE, et al. Diabetes Care. 2015;38(1):140-149. In the Participant Guide, please see Important Safety Information, including Boxed Warning about possible thyroid tumors incl uding thyroid cancer, the Full Prescribing Information, and Medication Guide. 8 Patients are reluctant to initiate injectable therapies1-3 Lifestyle burdens4,5 Patient beliefs surrounding injectable therapies Indication of disease progression1,4 Feelings of failure and guilt for not adhering to previous treatment1,4 Fearful and anxious about injections1,3 • Fear of needles3 • Fear of painful injections3,5 1. Joy SV. Diabetes Educ. 2008;34(suppl 3):54S-59S. 2. Öst LG. Behav Res Ther. 1991;29(4):323-332. 3. Rubin RR, et al. Diabetes Educ. 2009;35(6):1014-1022. 4. Korytkowski M. Int J Obesity. 2002;26(suppl 3):S18-S24. 5. Karter AJ, et al. Diabetes Care. 2010;33(4):733-735. In the Participant Guide, please see Important Safety Information, including Boxed Warning about possible thyroid tumors incl uding thyroid cancer, the Full Prescribing Information, and Medication Guide. 9 Once-weekly Trulicity™: the molecule • A recombinant GLP-1 Fc fusion protein linking a human GLP-1 peptide analog and a variant of a human IgG4-Fc fragment result in a 63-kDa molecule1 that met the following development goals2,3 – Once-weekly dosing1 GLP-1 analog • Extended plasma half-life (~5 days) • Minimal renal clearance1 Linker – Does not require reconstitution4 – Low immunogenicity1,2 • Percentage of patients who developed Trulicity antidrug antibodies in clinical studies was 1.6%1 Modified IgG4-Fc domain Fc = fragment crystallization; IgG = immunoglobulin G. 1. Trulicity [Prescribing Information]. Indianapolis, IN: Lilly USA, LLC; 2015. 2. Data on File. Eli Lilly and Company; 2014, TRU20140919A. 3. Umpierrez G, et al. Diabetes Obes Metab. 2011;13(5):418-425. 4. Trulicity [Instructions for Use]. Indianapolis, IN: Lilly USA, LLC; 2014. In the Participant Guide, please see Important Safety Information, including Boxed Warning about possible thyroid tumors incl uding thyroid cancer, the Full Prescribing Information, and Medication Guide. 10 Important Safety Information (continued) Hypersensitivity Reactions: Systemic reactions were observed in patients receiving Trulicity in clinical trials. Instruct patients who experience symptoms to discontinue Trulicity and promptly seek medical advice. Renal Impairment: In patients treated with GLP-1 RAs, there have been postmarketing reports of acute renal failure and worsening of chronic renal failure, sometimes requiring hemodialysis. A majority of reported events occurred in patients who had experienced nausea, vomiting, diarrhea, or dehydration. In patients with renal impairment, use caution when initiating or escalating doses of Trulicity and monitor renal function in patients experiencing severe adverse gastrointestinal reactions. Severe Gastrointestinal Disease: Use of Trulicity may be associated with gastrointestinal adverse reactions, sometimes severe. Trulicity has not been studied in patients with severe gastrointestinal disease, including severe gastroparesis, and is therefore not recommended in these patients. Trulicity [Prescribing Information]. Indianapolis, IN: Lilly USA, LLC; 2015. In the Participant Guide, please see Important Safety Information, including Boxed Warning about possible thyroid tumors incl uding thyroid cancer, the Full Prescribing Information, and Medication Guide. 11 Case study Jim* Meet Jim* Treatment considerations Frustrated He is Takes Currently small reluctant he istoman not to Time Family Busy Diabetes and add steps on dual to Goal Last A1C: visit achieving move to career duration: therapy in his keep manage OAM A1C: 7.0% 8.2% injectable diabetes him mid-50s 7but… years going diabetes therapy goals *Hypothetical patient. OAM = oral antihyperglycemic medication. Trulicity is not indicated for weight loss. Weight change was a secondary endpoint in clinical trials. In the Participant Guide, please see Important Safety Information, including Boxed Warning about possible thyroid tumors incl uding thyroid cancer, the Full Prescribing Information, and Medication Guide. 12 Given these considerations, what therapy might you add? • • • • • Efficacy Hypoglycemia Weight Major adverse reaction(s) Cost Add a DPP-4 inhibitor Add a GLP-1 RA Add insulin DPP-4 = dipeptidyl peptidase-4. In the Participant Guide, please see Important Safety Information, including Boxed Warning about possible thyroid tumors incl uding thyroid cancer, the Full Prescribing Information, and Medication Guide. 13 Once-weekly Trulicity compared to Januvia® (sitagliptin): AWARD-5 Design: 104‐week, randomized, placebo‐controlled, double‐blind phase 3 study of adult patients with type 2 diabetes Primary outcome measure: Noninferiority of Trulicity 1.5 mg to Januvia 100 mg on A1C change from baseline at 52 weeks Dose finding Primary time point Final time point Trulicity (mg) 0.25 0.50 Diabetes Duration Years (Mean) 7 Metformin Trulicity 0.75 mg Safety follow-up 7 1.0 Trulicity 1.5 mg 2.0 3.0 7 Januvia 100 mg 7 Placebo Januvia 100 mg Lead-in -11 Treatment period 0 26 52 Follow-up 104 108 Weeks All patients underwent a metformin run-in period that lasted up to 11 weeks and continued throughout the study; other oral antihyperglycemic medications were discontinued. During a dose-finding portion of the study, seven doses of Trulicity were evaluated along with sitagliptin and placebo. Trulicity 1.5 mg and 0.75 mg were selected for further evaluation and those patients assigned to the doses and comparators continued forward in the study. Recommended starting dose is 0.75 mg. Dose can be increased to 1.5 mg for additional glycemic control. AWARD = Assessment of Weekly AdministRation of LY2189265 in Diabetes. Nauck M, et al. Diabetes Care. 2014;37(8):2149-2158. In the Participant Guide, please see Important Safety Information, including Boxed Warning about possible thyroid tumors incl uding thyroid cancer, the Full Prescribing Information, and Medication Guide. 14 Mean A1C change from baseline (%) Trulicity showed superior A1C reduction* vs Januvia®1-3 Week 52 0 Januvia® (100 mg) (n=273; Baseline A1C: 8.0%) -0.2 Trulicity (0.75 mg) (n=281; Baseline A1C: 8.2%) -0.4 -0.6 -0.4 Trulicity (1.5 mg) (n=279; Baseline A1C: 8.1%) -0.8 -1.0 -1.2 -1.4 The most commonly reported treatment-emergent adverse events were gastrointestinal-related.1 -0.9† -1.1† -1.6 Data represent least-squares (LS) mean ± standard error (SE). *In clinical studies, the range of A1C reduction from baseline was 0.7% to 1.6% for the 0.75 mg dose and 0.8% to 1.6% for the 1.5 mg dose.1,4 Select Important Safety Information: Counsel patients regarding the risk of medullary thyroid carcinoma with Trulicity and the symptoms of thyroid tumors (eg, a mass in the neck, dysphagia, dyspnea, persistent hoarseness). Patients with elevated serum calcitonin (if measured) and patients with thyroid nodules noted on physical examination or neck imaging should be referred to an endocrinologist for further evaluation. †Multiplicity-adjusted 1-sided P value .001, for superiority of Trulicity compared to Januvia. Analysis of covariance using last observation carried forward (LOCF). 1. Trulicity [Prescribing Information]. Indianapolis, IN: Lilly USA, LLC; 2015. 2. Data on file, Lilly USA, LLC. TRU20150203B. 3. Data on file, Lilly USA, LLC. TRU20150203A. 4. Dungan et al. Lancet. 2014;384:1349-1357. In the Participant Guide, please see Important Safety Information, including Boxed Warning about possible thyroid tumors incl uding thyroid cancer, the Full Prescribing Information, and Medication Guide. 15 Trulicity 1.5 mg helped 59% of patients, and Trulicity 0.75 mg helped 49% of patients achieve A1C 7%1,2 100 Januvia® (100 mg) Patients achieving A1C 7.0% (%) (n=273; Baseline A1C: 8.0%) 90 Trulicity (0.75 mg) (n=281; Baseline A1C: 8.2%) 80 Trulicity (1.5 mg) 70 (n=279; Baseline A1C: 8.1%) 59%* 60 49%* 50 40 *P<0.001 Trulicity compared to Januvia.1 33% 30 20 10 0 52 weeks Data presented are secondary endpoints. In clinical studies, the percentage of patients achieving A1C 7% ranged from 37% to 69% for 0.75 mg and 53% to 78% for 1.5 mg.1,3-6 Select Important Safety Information: There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with Trulicity or any other antidiabetic drug. 1. Trulicity [Prescribing Information]. Indianapolis, IN: Lilly USA, LLC; 2015. 2. Data on file, Lilly USA, LLC. TRU20150203A. 3. Dungan KM et al. Lancet. 2014;384:1349-1357. 4. Umpierrez G. et al. Diabetes Care. 2014;37:2168-2176. 5. Giorgino F, et al. Presented at: American Diabetes Association Conference; San Francisco, CA: June 13-17, 2014. 6. Jendle J, et al. Presented at: American Diabetes Association Conference; San Francisco, CA; June 13-17, 2014. In the Participant Guide, please see Important Safety Information, including Boxed Warning about possible thyroid tumors incl uding thyroid cancer, the Full Prescribing Information, and Medication Guide. 16 Mean weight change from baseline (lb) Once-weekly Trulicity showed weight reduction compared to Januvia® at 52 weeks1-3 0 Januvia (100 mg) (n=273; Baseline Weight: 189.2 lb) -1 Trulicity (0.75 mg) (n=281; Baseline Weight: 188.5 lb) -2 Trulicity (1.5 mg) (n=279; Baseline Weight: 190.7 lb) -3 -4 -5 -3.3 -6 -7 -8 -6.0 -6.8 -9 -10 Data represent LS mean ± SE. Trulicity is not indicated for weight loss. In AWARD studies 1-5, weight change was a secondary endpoint. Mean weight change was -6.8 lb to -2.0 lb at the 1.5 mg dose and -6.0 lb to +0.4 lb at the 0.75 mg dose.1 Select Important Safety Information: Pancreatitis has been reported in clinical trials. Observe patients for signs and symptoms including persistent severe abdominal pain. If pancreatitis is suspected discontinue Trulicity promptly. Do not restart if pancreatitis is confirmed. Consider other antidiabetic therapies in patients with a history of pancreatitis. 1. Trulicity [Prescribing Information]. Indianapolis, IN: Lilly USA, LLC; 2015. 2. Data on file, Lilly USA, LLC. TRU20141010A. 3. Data on file, Lilly USA, LLC. TRU20150203A. In the Participant Guide, please see Important Safety Information, including Boxed Warning about possible thyroid tumors incl uding thyroid cancer, the Full Prescribing Information, and Medication Guide. 17 Incidence of hypoglycemia* In a head-to-head study with Januvia Add-on to metformin (26 weeks) Documented symptomatic Severe hypoglycemia† Placebo (n=177) Trulicity™ 0.75 mg (n=302) Trulicity 1.5 mg (n=304) 1.1% 2.6% 5.6% 0 0 0 *For study description, see slide 14. Documented symptomatic hypoglycemia was defined as 70 mg/dL glucose threshold. †Severe hypoglycemia is defined as an episode requiring the assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. Select Important Safety Information: The risk of hypoglycemia is increased when Trulicity is used in combination with insulin secretagogues (eg, sulfonylureas) or insulin. Patients may require a lower dose of sulfonylurea or insulin to reduce the risk of hypoglycemia. Trulicity [Prescribing Information]. Indianapolis, IN: Lilly USA, LLC; 2015. In the Participant Guide, please see Important Safety Information, including Boxed Warning about possible thyroid tumors incl uding thyroid cancer, the Full Prescribing Information, and Medication Guide. 18 Trulicity 1.5 mg compared to Victoza® (liraglutide) 1.8 mg: AWARD-6 Design: 26‐week, randomized, open‐label comparator phase 3 study of adult patients with type 2 diabetes Primary outcome measure: Noninferiority of Trulicity 1.5 mg vs Victoza 1.8 mg on A1C change from baseline at 26 weeks Final time point Randomization 7 Safety follow-up Metformin Diabetes Duration Years (Mean) Trulicity 1.5 mg once weekly + metformin Victoza 1.8 mg once daily + metformin 7 Lead-in -2 Treatment period 0 2 Week Follow-up 26 30 Victoza titration period Recommended starting dose is 0.75 mg. Dose can be increased to 1.5 mg for additional glycemic control. Dungan KM, et al. Lancet. 2014;384(9951):1349-1357. In the Participant Guide, please see Important Safety Information, including Boxed Warning about possible thyroid tumors incl uding thyroid cancer, the Full Prescribing Information, and Medication Guide. 19 Trulicity 1.5 mg demonstrated comparable A1C reduction to Victoza® 1.8 mg at 26 weeks1 8.2 8.0 LS mean A1C (%) ±SE Victoza (1.8 mg) (n=300; Baseline A1C: 8.1%) Primary objective was noninferiority vs Victoza 1.8 mg at 26 weeks; MMRM analysis. Primary objective met: P.0001. Secondary endpoint of superiority was not met. Trulicity (1.5 mg) (n=299; Baseline A1C: 8.1%) 7.8 Most common side effects were gastrointestinal. They were nausea, diarrhea, vomiting, and dyspepsia. 7.6 7.4 7.2 7.0 * 6.8 -1.36 -1.42 6.6 85% fewer injections2 6.4 Week 0 Week 8 Week 12 Week 26 Recommended starting dose of Trulicity is 0.75 mg. Dose can be increased to 1.5 mg for additional glycemic control. In clinical studies the range of A1C reduction from baseline was 0.7% to 1.6% for the 0.75 mg dose and 0.8% to 1.6% for the 1.5 mg dose.1,3 Select Important Safety Information: Use of Trulicity may be associated with gastrointestinal adverse reactions, sometimes severe. Trulicity has not been studied in and is not recommended for patients with a history of severe gastrointestinal disease (eg, severe gastroparesis). Consistent with product labeling, patients randomized to Victoza started at 0.6 mg/day in week 1, then were up-titrated to 1.2 mg/day in week 2 and to 1.8 mg/day in week 3. *American Diabetes Association recommended target goal. Treatment should be individualized.4 MMRM = mixed models, repeated measures. 1. Dungan KM, et al. Lancet. 2014;384(9951):1349-1357. 2. Data on file, Lilly USA, LLC. TRU20140919B. 3. Trulicity [Prescribing Information]. Indianapolis, IN: Lilly USA, LLC; 2015. 4. American Diabetes Association. Diabetes Care 2015;38(Suppl. 1):S1-S93. In the Participant Guide, please see Important Safety Information, including Boxed Warning about possible thyroid tumors incl uding thyroid cancer, the Full Prescribing Information, and Medication Guide. 20 Trulicity 1.5 mg helped 68% of patients achieve A1C 7% at 26 weeks1 Percentage of patients achieving A1C 7% 100 Victoza® (1.8 mg) (n=300; Baseline A1C: 8.1%) 90 Trulicity (1.5 mg) (n=299; Baseline A1C: 8.1%) 80 70 68% 68% 60 Most common side effects were gastrointestinal. They were nausea, diarrhea, vomiting, and dyspepsia. 50 40 30 20 10 0 Data presented are secondary endpoints. Recommended starting dose of Trulicity is 0.75 mg. Dose can be increased to 1.5 mg. In clinical studies, the percentage of patients achieving A1C 7% ranged from 37% to 69% for 0.75 mg and 53% to 78% for 1.5 mg.1-5 Select Important Safety Information: Systemic hypersensitivity reactions were observed in patients receiving Trulicity in clinical trials. Instruct patients who experience symptoms to discontinue Trulicity and promptly seek medical advice. Consistent with product labeling, patients randomized to Victoza started at 0.6 mg/day in week 1, then were up-titrated to 1.2 mg/day in week 2 and to 1.8 mg/day in week 3. 1. Dungan KM, et al. Lancet. 2014;384(9951):1349-1357. 2. Trulicity [Prescribing Information]. Indianapolis, IN: Lilly USA, LLC; 2015. 3. Umpierrez G. et al. Diabetes Care. 2014;37:2168-2176. 4. Giorgino F, et al. Presented at: American Diabetes Association Conference; San Francisco, CA: June 13-17, 2014. 5. Jendle J, et al. Presented at: American Diabetes Association Conference; San Francisco, CA; June 13-17, 2014. In the Participant Guide, please see Important Safety Information, including Boxed Warning about possible thyroid tumors incl uding thyroid cancer, the Full Prescribing Information, and Medication Guide. 21 Mean weight change from baseline (lb) Once-weekly Trulicity 1.5 mg showed weight reduction at 26 weeks1 Victoza® (1.8 mg) (n=300; Baseline weight: 208.1 lb) 0 -1 Trulicity (1.5 mg) (n=299; Baseline weight: 206.8 lb) -2 Weight change was a secondary endpoint -3 -4 -5 -6 -7 -6.39 -8 -9 -7.96 -10 Data represent LS mean ± SE. Trulicity is not indicated for weight loss. In AWARD studies 1-5, weight change was a secondary endpoint. Mean weight change was -6.8 lb to -2.0 lb at the 1.5 mg dose and -6.0 lb to +0.4 lb at the 0.75 mg dose.2 Select Important Safety Information: There have been postmarketing reports of acute renal failure and worsening of chronic renal failure, sometimes requiring hemodialysis, in patients treated with GLP‐1 receptor agonists. A majority of reported events occurred in patients who had experienced nausea, vomiting, diarrhea, or dehydration. In patients with renal impairment, use caution when initiating or escalating doses of Trulicity and monitor renal function in patients experiencing severe adverse gastrointestinal reactions. Consistent with product labeling, patients randomized to Victoza started at 0.6 mg/day in week 1, then were up-titrated to 1.2 mg/day in week 2 and to 1.8 mg/day in week 3. 1. Dungan KM, et al. Lancet. 2014;384(9951):1349-1357. 2. Trulicity [Prescribing Information]. Indianapolis, IN: Lilly USA, LLC; 2015. In the Participant Guide, please see Important Safety Information, including Boxed Warning about possible thyroid tumors incl uding thyroid cancer, the Full Prescribing Information, and Medication Guide. 22 Incidence of hypoglycemia* In a head-to-head study with Victoza® 1.8 mg Add-on to metformin (26 weeks) Victoza 1.8 mg (n=300) Trulicity™ 1.5 mg (n=299) Total hypoglycemia 6% 9% Total hypoglycemia: Events/patient/year 0.5 0.3 0 0 Severe hypoglycemia† *For study description, see slide 19. Documented symptomatic hypoglycemia was defined as 70 mg/dL glucose threshold. †Severe hypoglycemia is defined as an episode requiring the assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. Select Important Safety Information: The risk of hypoglycemia is increased when Trulicity is used in combination with insulin secretagogues (eg, sulfonylureas) or insulin. Patients may require a lower dose of sulfonylurea or insulin to reduce the risk of hypoglycemia. Dungan KM, et al. Lancet. 2014;384(9951):1349-1357. In the Participant Guide, please see Important Safety Information, including Boxed Warning about possible thyroid tumors incl uding thyroid cancer, the Full Prescribing Information, and Medication Guide. 23 Setting expectations and starting once-weekly Trulicity Important Safety Information (continued) Macrovascular Outcomes: There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with Trulicity or any other antidiabetic drug. The most common adverse reactions reported in 5% of Trulicity-treated patients in placebocontrolled trials (placebo, Trulicity 0.75 mg, and Trulicity 1.5 mg) were nausea (5.3%, 12.4%, 21.1%), diarrhea (6.7%, 8.9%, 12.6%), vomiting (2.3%, 6.0%, 12.7%), abdominal pain (4.9%, 6.5%, 9.4%), decreased appetite (1.6%, 4.9%, 8.6%), dyspepsia (2.3%, 4.1%, 5.8%), and fatigue (2.6%, 4.2%, 5.6%). Gastric emptying is slowed by Trulicity, which may impact absorption of concomitantly administered oral medications. Use caution when oral medications are used with Trulicity. Drug levels of oral medications with a narrow therapeutic index should be adequately monitored when concomitantly administered with Trulicity. In clinical pharmacology studies, Trulicity did not affect the absorption of the tested, orally administered medications to a clinically relevant degree. Trulicity [Prescribing Information]. Indianapolis, IN: Lilly USA, LLC; 2015. In the Participant Guide, please see Important Safety Information, including Boxed Warning about possible thyroid tumors incl uding thyroid cancer, the Full Prescribing Information, and Medication Guide. 25 Trulicity reduced fasting glucose levels1-3 Weeks FPG change from baseline (mg/dL, LS mean ± SE) 0 2 4 8 12 26 39 52 10 Placebo (n=139; Baseline FPG: 179 mg/dL) 0 Januvia® (100mg) (n=273; Baseline FPG: 171 mg/dL) -10 Trulicity (0.75 mg) (n=281; Baseline FPG: 174 mg/dL) -20 -30 Trulicity (1.5 mg) (n=279; Baseline FPG: 173 mg/dL) A Data presented are secondary endpoints. Placebo was replaced with Januvia after 26 weeks to keep blinding. -40 -50 104-week, randomized, placebo-controlled, double-blind phase 3 study of adult patients with type 2 diabetes treated with metformin 1500 mg. Primary objective was to demonstrate noninferiority of Trulicity 1.5 mg vs Januvia on A1C change from baseline at 52 weeks (-1.1% vs -0.4%, respectively; difference of -0.7%; 95% CI [-0.9, -0.5]; multiplicity-adjusted 1-sided alpha level of 0.025 for noninferiority with 0.25% margin; analysis of covariance using last observation carried forward); primary objective met Select Important Safety Information: Use of Trulicity may be associated with gastrointestinal adverse reactions, sometimes severe. Trulicity has not been studied in and is not recommended for patients with a history of severe gastrointestinal disease (eg, severe gastroparesis). FPG = fasting plasma glucose. 1. Trulicity [Prescribing Information]. Indianapolis, IN: Lilly USA, LLC; 2015. 2. Data on file, Lilly USA, LLC. TRU20150130A. 3. Data on file, Lilly USA, LLC. TRU20150203A. In the Participant Guide, please see Important Safety Information, including Boxed Warning about possible thyroid tumors incl uding thyroid cancer, the Full Prescribing Information, and Medication Guide. 26 Placebo-adjusted LS mean change from baseline in PPG (mg/dL) Trulicity reduced 2-hour postprandial glucose levels1,2 0 Trulicity (0.75 mg) (n=11) -10 Trulicity (1.5 mg) (n=9) -20 -30 -40 -39.8 -50 -60 -59.5 -70 6-week, multicenter, parallel-design, double-blind, part-randomized, placebo-controlled, multiple-dose, phase 1 study in patients 65 years old with type 2 diabetes treated with oral antihyperglycemic medications except sulfonylureas, disaccharidase inhibitors, and meglitinides. Study arms included placebo (n=8); Trulicity 0.5 mg (n=9), not a marketed dose; Trulicity 0.75 mg (n=11); and Trulicity 1.5 mg (n=9). Primary objective was to evaluate the safety and tolerability of Trulicity 0.5 mg, 0.75 mg, and 1.5 mg for 6 weeks; mixed effect linear model; primary objective met. Data presented are secondary endpoints and show change in 2-hour postprandial plasma glucose concentration 48 hours after the first dose of Trulicity. Select Important Safety Information: Trulicity slows gastric emptying, which may impact absorption of concomitantly administered oral medications. Use caution when oral medications are administered with Trulicity. Monitor drug levels of oral medications with a narrow therapeutic index when concomitantly administered. In clinical pharmacology studies, Trulicity did not affect the absorption of the tested, orally administered medications to a clinically relevant degree. PPG = postprandial glucose. 1. Data on file, Lilly USA, LLC. TRU20140912F. 2. Trulicity [Prescribing Information]. Indianapolis, IN: Lilly USA, LLC; 2015. In the Participant Guide, please see Important Safety Information, including Boxed Warning about possible thyroid tumors incl uding thyroid cancer, the Full Prescribing Information, and Medication Guide. 27 Adverse reactions in placebo-controlled studies through 26 weeks, reported in 5% of Trulicity-treated patients Adverse reaction (through 26 weeks) Placebo (N=568) Trulicity 0.75 mg (N=836) Trulicity 1.5 mg (N=834) Nausea (%) 5.3 12.4 21.1 Vomiting (%)* 2.3 6.0 12.7 Diarrhea (%)* 6.7 8.9 12.6 Abdominal pain (%)* 4.9 6.5 9.4 Decreased appetite (%) 1.6 4.9 8.6 Dyspepsia (%) 2.3 4.1 5.8 Fatigue (%)* 2.6 4.2 5.6 *Adverse reaction term represents 1 preferred MedDRA terms, clustered under a single, common term. Note: Percentages reflect the number of patients that reported at least 1 treatment-emergent occurrence of the adverse reaction. Select Important Safety Information: Pancreatitis has been reported in clinical trials. Observe patients for signs and symptoms including persistent severe abdominal pain. If pancreatitis is suspected discontinue Trulicity promptly. Do not restart if pancreatitis is confirmed. Consider other antidiabetic therapies in patients with a history of pancreatitis. Trulicity [Prescribing Information]. Indianapolis, IN: Lilly USA, LLC; 2015. In the Participant Guide, please see Important Safety Information, including Boxed Warning about possible thyroid tumors incl uding thyroid cancer, the Full Prescribing Information, and Medication Guide. 28 Common side effects your patient may experience The most common adverse reactions in clinical trials were GI in nature GI events were usually reported as mild or moderate Discontinuation rates due to GI adverse reactions 32% for 0.75 mg 93% for 0.75 mg 1.3% for 0.75 mg 41% for 1.5 mg 90% for 1.5 mg 3.5% for 1.5 mg 21% for placebo N/A 0.2% for placebo Select Important Safety Information: There have been postmarketing reports of acute renal failure and worsening of chronic renal failure, sometimes requiring hemodialysis, in patients treated with GLP-1 receptor agonists. A majority of reported events occurred in patients who had experienced nausea, vomiting, diarrhea, or dehydration. In patients with renal impairment, use caution when initiating or escalating doses of Trulicity and monitor renal function in patients experiencing severe adverse gastrointestinal reactions. Use of Trulicity may be associated with gastrointestinal adverse reactions, sometimes severe. Trulicity has not been studied in and is not recommended for patients with a history of severe gastrointestinal disease (eg, severe gastroparesis). Trulicity [Prescribing Information]. Indianapolis, IN: Lilly USA, LLC; 2015. In the Participant Guide, please see Important Safety Information, including Boxed Warning about possible thyroid tumors incl uding thyroid cancer, the Full Prescribing Information, and Medication Guide. 29 When patients need additional A1C control, consider adding Trulicity along with diet and exercise Trulicity offers your patients1 • Once-weekly dosing • The Trulicity pen • Proven glycemic control* Recommended starting dose is 0.75 mg. Dose can be increased to 1.5 mg for additional glycemic control. *In clinical studies, the range of A1C reduction from baseline was 0.7% to 1.6% for the 0.75 mg dose and 0.8% to 1.6% for the 1.5 mg dose; the percentage of patients achieving A1C 7% ranged from 37% to 69% for 0.75 mg and 53% to 78% for 1.5 mg.1-5 Select Important Safety Information: Trulicity is contraindicated in patients with a personal or family history of medullary thyroid carcinoma or in patients with Multiple Endocrine Neoplasia syndrome type 2. 1. Trulicity [Prescribing Information]. Indianapolis, IN: Lilly USA, LLC; 2015. 2. Dungan KM et al. Lancet. 2014;384:1349-1357. 3. Umpierrez G. et al. Diabetes Care. 2014;37:2168-2176. 4. Giorgino F, et al. Presented at: American Diabetes Association Conference; San Francisco, CA: June 13-17, 2014. 5. Jendle J, et al. Presented at: American Diabetes Association Conference; San Francisco, CA; June 13-17, 2014. In the Participant Guide, please see Important Safety Information, including Boxed Warning about possible thyroid tumors incl uding thyroid cancer, the Full Prescribing Information, and Medication Guide. 30 Designed with your patients in mind1-3 Trulicity offers • Once-weekly dosing • No reconstitution required • Hidden 29-gauge needle4 • No need to dial a dose In a study of 128 patients, caregivers, and healthcare providers, most people agreed the Trulicity pen was overall easy to use.5 Please see Instructions for Use included with the pen. Easy to use 94% Select Important Safety Information: Safety and effectiveness of Trulicity have not been established in pediatric patients. It is not recommended for use in patients younger than 18 years. 1. Trulicity [Prescribing Information]. Indianapolis, IN: Lilly USA, LLC; 2015. 2. Trulicity [Instructions for Use]. Indianapolis, IN: Lilly USA, LLC; 2014. 3. Glaesner W, et al. Diabetes Metab Res Rev. 2010;26(4):287-296. 4. Data on file, Lilly USA, LLC. TRU20140918A. 5. Data on file, Lilly USA, LLC. TRU20140910L. In the Participant Guide, please see Important Safety Information, including Boxed Warning about possible thyroid tumors incl uding thyroid cancer, the Full Prescribing Information, and Medication Guide. 31 Prescribing once-weekly Trulicity There are 2 efficacious doses available • The recommended starting dosage of Trulicity is 0.75 mg once a week • For patients requiring additional glycemic control, the dosage may be increased to 1.5 mg once a week 0.75 mg dose 1.5 mg dose [NDC: 0002-1433-80] [NDC: 0002-1434-80] Recommended starting dose Should your patient need more glycemic control Select Important Safety Information: There are no adequate and well-controlled studies of Trulicity in pregnant women. Use only if the potential benefit outweighs potential risk to the fetus. It is not known whether Trulicity is excreted in human milk. A decision should be made whether to discontinue nursing or to discontinue Trulicity, taking into account the importance of the drug to the mother. Trulicity [Prescribing Information]. Indianapolis, IN: Lilly USA, LLC; 2015. In the Participant Guide, please see Important Safety Information, including Boxed Warning about possible thyroid tumors incl uding thyroid cancer, the Full Prescribing Information, and Medication Guide. 32 Important Safety Information (continued) Pregnancy: There are no adequate and well-controlled studies of Trulicity in pregnant women. Use only if potential benefit outweighs potential risk to fetus. Nursing Mothers: It is not known whether Trulicity is excreted in human milk. A decision should be made whether to discontinue nursing or to discontinue Trulicity, taking into account the importance of the drug to the mother. Pediatric Use: Safety and effectiveness of Trulicity have not been established and use is not recommended in patients less than 18 years of age. Please see accompanying Participant Guide for Prescribing Information, including Boxed Warning about possible thyroid tumors including thyroid cancer, and Medication Guide. Please see Instructions for Use included with the pen. DG HCP ISI 20APR2015 Byetta® is a registered trademark of the AstraZeneca group of companies. Januvia® is a registered trademark of Merck & Co., Inc. Lantus® is a registered trademark of sanofi-aventis U.S. LLC. Trulicity™ is a trademark owned or licensed by Eli Lilly and Company, its subsidiaries or affiliates. Trulicity is available by prescription only. Victoza® is a registered trademark of Novo Nordisk A/S. Trulicity [Prescribing Information]. Indianapolis, IN: Lilly USA, LLC; 2015. In the Participant Guide, please see Important Safety Information, including Boxed Warning about possible thyroid tumors incl uding thyroid cancer, the Full Prescribing Information, and Medication Guide. 33 THANK YOU In the Participant Guide, please see Important Safety Information, including Boxed Warning about possible thyroid tumors incl uding thyroid cancer, the Full Prescribing Information, and Medication Guide. 34 Appendix: overview of efficacy Clinical trial program Monotherapy Active Comparator Background therapy Primary objective Study design Trial 2-drug combinations 3-drug combinations Insulin Metformin Januvia® Victoza® Byetta® Lantus® (1500-2000 mg) (sitagliptin) 100 mg/d (liraglutide) 1.8 mg/d (exenatide) 10 mcg BID (insulin glargine) None (monotherapy) Met 1500 mg (titrated over 11-week lead-in) Met 1500 mg Met + Pio (maximally tolerated doses) Met + SU (maximally tolerated doses) Prandial insulin lispro (titrated to BG targets) ± met Noninferiority of Trulicity 1.5 mg vs metformin on A1C change from baseline at 26 weeks Noninferiority of highest selected dose vs Januvia on A1C change from baseline at 52 weeks Noninferiority of Trulicity 1.5 mg vs Victoza on A1C change from baseline at 26 weeks Superiority of Trulicity 1.5 mg vs placebo on A1C change from baseline at 26 weeks Noninferiority of Trulicity 1.5 mg vs Lantus* on A1C change from baseline at 52 weeks Noninferiority of Trulicity 1.5 mg vs Lantus* on A1C change from baseline at 26 weeks Randomized, double-blind study Randomized, placebo-controlled, double-blind study Randomized, open-label comparator study AWARD-31 (N=807) AWARD-51 (N=972) AWARD-62 (N=599) Lantus Randomized, Randomized, Randomized, placebo-controlled open-label comparator open-label comparator study with open-label study (double-blind study (double-blind assignments to Byetta with respect with respect or blinded assignment to Trulicity to Trulicity to Trulicity or placebo dose assignment) dose assignment) AWARD-11 (N=976) AWARD-21 (N=807) AWARD-41 (N=884) *Titrated to FPG target of 100 mg/dL. Met = metformin; Pio = pioglitazone; SU = sulfonylurea; BG = blood glucose. 1. Trulicity [Prescribing Information]. Indianapolis, IN: Lilly USA, LLC; 2015. 2. Dungan KM, et al. Lancet. 2014;384(9951):1349-1357. In the Participant Guide, please see Important Safety Information, including Boxed Warning about possible thyroid tumors incl uding thyroid cancer, the Full Prescribing Information, and Medication Guide. 36 A1C reduction across trials at primary endpoint Compared to Januvia®1-3 A1C change from baseline (%) 0 Add-on to metformin (52 weeks) Compared to Victoza®4 Add-on to metformin (26 weeks) Compared to Byetta®1,5 Compared to Lantus®1,6,7,8 Add-on to metformin and pioglitazone (26 weeks) Add-on to metformin and glimepiride (52 weeks) -0.2 -0.4 -0.39 -0.6 -0.46 -0.63 -0.8 -0.76 -1.0 -1.2 -0.87 -0.99 -1.08 -1.10 -1.4 -1.36 -1.6 -1.30 -1.42 -1.8 -1.51 Placebo Data represent LS mean±SE (n=141; Baseline A1C: 8.1%) Januvia (100 mg) Victoza (1.8 mg) Byetta (10 mcg BID) Lantus (n=273; Baseline A1C: 8.0%) (n=300; Baseline A1C: 8.1%) (n=276; Baseline A1C: 8.1%) (n=262; Baseline A1C: 8.1%) Trulicity (0.75 mg) Trulicity (1.5 mg) Trulicity (0.75 mg) Trulicity (0.75 mg) (n=281; Baseline A1C: 8.2%) (n=299; Baseline A1C: 8.1%) (n=280; Baseline A1C: 8.1%) (n=272; Baseline A1C: 8.1%) Trulicity (1.5 mg) Trulicity (1.5 mg) Trulicity (1.5 mg) (n=279; Baseline A1C: 8.1%) (n=279; Baseline A1C: 8.1%) (n=273; Baseline A1C: 8.2%) *In clinical studies, the range of A1C reduction from baseline was 0.7% to 1.6% for the 0.75 mg dose and 0.8% to 1.6% for the 1.5 mg dose.1,4 Select Important Safety Information: Systemic hypersensitivity reactions were observed in patients receiving Trulicity in clinical trials. Instruct patients who experience symptoms to discontinue Trulicity and promptly seek medical advice. 1. Trulicity [Prescribing Information]. Indianapolis, IN: Lilly USA, LLC; 2015. 2. Data on file, Lilly USA, LLC. TRU20150203A. 3. Data on file, Lilly USA, LLC. TRU20150203B. 4. Dungan KM, et al. Lancet. 2014;384:1349-1357. 5. Wysham C, et al. Diabetes Care. 2014;37:2159-2167. 6. Giorgino F, et al. Presented at: American Diabetes Association Conference; San Francisco, CA: June 13-17, 2014. 7. Data on file, Lilly USA, LLC. TRU20140912A. 8. Data on file, Lilly USA, LLC. TRU20150313A. In the Participant Guide, please see Important Safety Information, including Boxed Warning about possible thyroid tumors incl uding thyroid cancer, the Full Prescribing Information, and Medication Guide. 37 Mean weight change from baseline (lb) Patients may have the opportunity to lose weight while taking Trulicity to lower their A1C1 4 3 2 1 0 -1 -2 -3 -4 -5 -6 -7 -8 -9 -10 Compared to Januvia®1-3 Compared to Victoza®4 Compared to Byetta®1,5 Compared to Lantus®1,6-8 Add-on to metformin (52 weeks) Add-on to metformin (26 weeks) Add-on to metformin and pioglitazone (26 weeks) Add-on to metformin and glimepiride (52 weeks) +3.1 +2.6 +0.4 -2.4 -3.3 -2.9 -2.9 -4.2 -6.0 -6.39 -6.8 -7.96 Data represent LS mean±SE. Januvia (100 mg) Placebo (n=141; Baseline weight: 207.5 lb) Victoza (1.8 mg) (n=273; Baseline weight:189.2 lb) (n=300; Baseline weight: 208.1 lb) Trulicity (0.75 mg) Trulicity (1.5 mg) (n=281; Baseline weight:188.5 lb) (n=299; Baseline weight: 206.8 lb) Trulicity (1.5 mg) (n=279; Baseline weight:190.7 lb) Byetta (10 mcg BID) (n=276; Baseline weight: 214.7 lb) Trulicity (0.75 mg) (n=280; Baseline weight: 210.5 lb) Trulicity (1.5 mg) (n=279; Baseline weight: 212.1 lb) Lantus (n=262; Baseline weight: 193.1 lb) Trulicity (0.75 mg) (n=272; Baseline weight: 190.5 lb) Trulicity (1.5 mg) (n=273; Baseline weight: 187.8 lb) Trulicity is not indicated for weight loss. In AWARD studies 1-5, weight change was a secondary endpoint. Mean weight change was -6.8 lb to -2.0 lb at the 1.5 mg dose and -6.0 lb to +0.4 lb at the 0.75 mg dose1 Select Important Safety Information: There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with Trulicity or any other antidiabetic drug. 1. Trulicity [Prescribing Information]. Indianapolis, IN: Lilly USA, LLC; 2015. 2. Data on file, Lilly USA, LLC. TRU20141010A. 3. Data on file, Lilly USA, LLC. TRU20150203A. 4. Dungan KM, et al. Lancet. 2014;384(9951):1349-1357. 5. Wysham C, et al. Diabetes Care. 2014;37(8):2159-2167. 6. Giorgino F, et al. Presented at: American Diabetes Association Conference; San Francisco, CA: June 13-17, 2014. 7. Data on file, Lilly USA, LLC. TRU20140912B. 8. Data on file, Lilly USA, LLC. TRU20150313A. In the Participant Guide, please see Important Safety Information, including Boxed Warning about possible thyroid tumors incl uding thyroid cancer, the Full Prescribing Information, and Medication Guide. 38 Back-up slides Epidemiology and burden of diabetes in the US DIABETES AFFECTS 29.1 MILLION OR ~1 IN 11 PEOPLE OF ALL AGES1 • Diagnosed: 21.0 million 1.7 million 20 years of age newly diagnosed in 2012 In adults, type 2 diabetes accounts for ~90-95% of all diagnosed cases of diabetes • Undiagnosed: 8.1 million ESTIMATED CO STS $245 BILLION IN 20121 EVERY 19 SECONDS SOMEONE is DIAGNOSED WITH DIABETES 2 • Direct medical costs: $176 billion • Indirect societal costs: $69 billion 1. Centers for Disease Control and Prevention. National Diabetes Statistics Report: Estimates of Diabetes and Its Burden in the United States, 2014. 2. ADA. Diabetes by the Numbers. http://www.stopdiabetes.com/get-the-facts/diabetes-by-thenumbers.html. Updated October 24, 2014. Accessed May 5, 2015. In the Participant Guide, please see Important Safety Information, including Boxed Warning about possible thyroid tumors incl uding thyroid cancer, the Full Prescribing Information, and Medication Guide. 40 American Diabetes Association/EASD general therapy recommendations in type 2 diabetes* Healthy eating, weight control, increased physical activity, and diabetes education Monotherapy Metformin high low risk neutral / loss GI / lactic acidosis low Efficacy Hypo risk Weight Side effects Costs If HbA1C target not achieved after ~3 months of monotherapy, proceed to 2-drug combination (order not meant to denote any specific preference—choice dependent on a variety of patient- and disease-specific factors): Dual therapy Efficacy Hypo risk Weight Side effects Costs Metformin Metformin Metformin Metformin Metformin Metformin + + + + + + Sulfonylurea Thiazolidinedione DPP-4 inhibitor SGLT2 inhibitor high moderate risk gain hypoglycemia low high low risk gain edema, HF, fxs low intermediate low risk neutral rare high intermediate low risk loss GU, dehydration high GLP-1 receptor agonist high low risk loss GI high Insulin (basal) highest high risk gain hypoglycemia variable If HbA1c target not achieved after ~3 months of dual therapy, proceed to 3-drug combination (order not meant to denote any specific preference—choice dependent on a variety of patient- and disease-specific factors):: Metformin Triple therapy Metformin + Sulfonylurea Metformin DPP-4 inhibitor SGLT2 inhibitor + TZD DPP-4-i SGLT2-i GLP-1-RA Insulin SU DPP-4-i SGLT2-i GLP-1-RA or or or GLP-1 receptor agonist SGLT2-i Insulin or or or Insulin (basal) + + SU TZD Metformin + + + + SU or or or or Metformin + + Thiazolidinedione + or or or or Metformin + TZD DPP-4-i SU or or Insulin TZD Insulin TZD or or or DPP-4-i SGLT2-i GLP-1-RA Insulin If HbA1C target not achieved after ~3 months of triple therapy and patient (1) on oral combination, move to injectables; (2) on GLP-1-RA, add basal insulin; or (3) on optimally titrated basal insulin, add GLP-1-RA or mealtime insulin. In refractory patients consider adding TZD or SGLT2-i: Combination injectable therapy Trulicity™ has not been studied in combination with basal insulin. Metformin + Basal insulin + Mealtime insulin or GLP-1-RA *Adapted from Inzucchi SE, et al. Diabetes Care. 2015;38(1):140-149. HbA1C = glycated hemoglobin; DPP-4-i = dipeptidyl peptidase-4 inhibitor; EASD = European Association for the Study of Diabetes; fxs = fractures; GU = genito-urinary infections; HF = heart failure; SU = sulfonylurea; TZD = thiazolidinedione. Inzucchi SE, et al. Diabetes Care. 2015;38(1):140-149. In the Participant Guide, please see Important Safety Information, including Boxed Warning about possible thyroid tumors incl uding thyroid cancer, the Full Prescribing Information, and Medication Guide. 41 Individualizing treatment goals in type 2 diabetes* PATIENT/DISEASE FEATURES Risks potentially associated with hypoglycemia and other drug adverse effects Disease duration Life expectancy Important comorbidities Established vascular complications Patient attitude and expected treatment efforts Resources and support system More stringent HbA1c 7% Less stringent Low High Long-standing Newly diagnosed Long Short Absent few/mild Severe Absent few/mild Severe Highly motivated, adherent, excellent self-care capacities Less motivated, nonadherent, poor self-care capacities Readily available Usually not modifiable Potentially modifiable Limited This approach is not designed to be applied rigidly but to be used as a broad construct to help guide clinical decisions. *Adapted from Inzucchi SE, et al. Diabetes Care. 2015;38(1):140-149. Inzucchi SE, et al. Diabetes Care. 2015;38(1):140-149. In the Participant Guide, please see Important Safety Information, including Boxed Warning about possible thyroid tumors incl uding thyroid cancer, the Full Prescribing Information, and Medication Guide. 42 Once-weekly Trulicity compared to Lantus® (insulin glargine): AWARD-21 Design: 78‐week, randomized, open‐label comparator phase 3 study (double‐blind with respect to Trulicity dose assignment) of adult patients with type 2 diabetes Primary outcome measure: A1C change from baseline at 52 weeks Primary time point Randomization Final time point 9 9 Safety follow-up Metformin + glimepiride Diabetes Duration Years (Mean) Trulicity 1.5 mg Trulicity 0.75 mg 9 Insulin glargine Screening -12-10 Lead-in Treatment period 0 Weeks Follow-up 52 78 82 Recommended starting dose is 0.75 mg. Dose can be increased to 1.5 mg for additional glycemic control. In clinical studies, the range of A1C reduction from baseline was 0.7% to 1.6% for the 0.75 mg dose and 0.8% to 1.6% for the 1.5 mg dose.2,3 1. Giorgino F, et al. Presented at: American Diabetes Association Conference; San Francisco, CA: June 13-17, 2014. 2. Trulicity [Prescribing Information]. Indianapolis, IN: Lilly USA, LLC; 2015. 3. Dungan KM, et al. Lancet. 2014;384(9951):1349-1357. In the Participant Guide, please see Important Safety Information, including Boxed Warning about possible thyroid tumors incl uding thyroid cancer, the Full Prescribing Information, and Medication Guide. 43 Mean change in A1C (%) Once-weekly Trulicity demonstrated A1C reduction from baseline in a study compared to Lantus®1 0.0 Lantus (n=262; Baseline A1C: 8.1%) -0.2 Trulicity (0.75 mg) (n=272; Baseline A1C: 8.1%) -0.4 Trulicity (1.5 mg) (n=273; Baseline A1C: 8.2%) -0.6 -0.8 -1.0 -0.6 -0.8 -1.2 -1.1 -1.4 Data represent LS mean ± SE. Recommended starting dose is 0.75 mg. Dose can be increased to 1.5 mg. In clinical studies, the range of A1C reduction from baseline was 0.7% to 1.6% for the 0.75 mg dose and 0.8% to 1.6% for the 1.5 mg dose.1,2 Select Important Safety Information: Safety and effectiveness of Trulicity have not been established in pediatric patients. It is not recommended for use in patients younger than 18 years. 1. Trulicity [Prescribing Information]. Indianapolis, IN: Lilly USA, LLC; 2015. 2. Dungan KM, et al. Lancet. 2014;384:1349-1357. In the Participant Guide, please see Important Safety Information, including Boxed Warning about possible thyroid tumors incl uding thyroid cancer, the Full Prescribing Information, and Medication Guide. 44 Mean weight change from baseline (lb) Once-weekly Trulicity showed weight reduction compared to Lantus® at 52 weeks1-3 4 +3.1 Lantus (n=262; Baseline weight: 193.1 lb) 3 Trulicity (0.75 mg) (n=272; Baseline weight: 190.5 lb) 2 1 Trulicity (1.5 mg) (n=273; Baseline weight: 187.8 lb) 0 -1 -2 -3 -4 -5 -2.9 -4.2 -6 -7 Data represent LS mean ± SE. Trulicity is not indicated for weight loss. In AWARD studies 1-5, weight change was a secondary endpoint. Mean weight change was -6.8 lb to -2.0 lb at the 1.5 mg dose and -6.0 lb to +0.4 lb at the 0.75 mg dose.1 Select Important Safety Information: There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with Trulicity or any other antidiabetic drug. 1. Trulicity [Prescribing Information]. Indianapolis, IN: Lilly USA, LLC; 2015. 2. Data on file, Lilly USA, LLC. TRU20140912B. 3. Data on file, Lilly USA, LLC. TRU20150313A. In the Participant Guide, please see Important Safety Information, including Boxed Warning about possible thyroid tumors incl uding thyroid cancer, the Full Prescribing Information, and Medication Guide. 45 Incidence of hypoglycemia* In a head-to-head study with Lantus®1-2 Add-on to metformin + glimepiride (52 weeks) Documented symptomatic (events/patient/year) Severe hypoglycemia†, n (%) Lantus (n=262) Trulicity™ 0.75 mg (n=272) Trulicity 1.5 mg (n=273) 3.02 1.67 1.67 2 (0.8) 0 (0.0) 2 (0.7) *For study description, see slide 43. Documented symptomatic hypoglycemia was defined as 70 mg/dL glucose threshold. †Severe hypoglycemia is defined as an episode requiring the assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. Trulicity is not indicated for weight loss. Recommended starting dose is 0.75 mg. Dose can be increased to 1.5 mg. In clinical studies, the range of A1C reduction from baseline was 0.7% to 1.6% for the 0.75 mg dose and 0.8% to 1.6% for the 1.5 mg dose.1,3 Select Important Safety Information: The risk of hypoglycemia is increased when Trulicity is used in combination with insulin secretagogues (eg, sulfonylureas) or insulin. Patients may require a lower dose of sulfonylurea or insulin to reduce the risk of hypoglycemia. 1. Trulicity [Prescribing Information]. Indianapolis, IN: Lilly USA, LLC; 2015. CA. 2. Data on file, Lilly USA, LLC. TRU20140915B. 3. Dungan KM, et al. Lancet. 2014;384:1349-1357. In the Participant Guide, please see Important Safety Information, including Boxed Warning about possible thyroid tumors incl uding thyroid cancer, the Full Prescribing Information, and Medication Guide. 32 Getting your patients started on once-weekly Trulicity Your patients should be aware of the safety and efficacy information for the product and be trained on proper injection technique. Get your patients off to a good start with the Trulicity sample pack. The pack includes: • A savings card to help eligible commercially covered patients save money (pay as little as $25*) on their prescription • Educational information so your patients have support once they are home and preparing for their first dose • Two sample pens for your patients’ first two weeks on Trulicity *For each of your patient’s first 26 prescriptions, Lilly pays up to $150 per month depending on insurance coverage. Only for those who do not receive government reimbursement for their prescriptions. Other terms and restrictions apply. In the Participant Guide, please see Important Safety Information, including Boxed Warning about possible thyroid tumors incl uding thyroid cancer, the Full Prescribing Information, and Medication Guide. 47