Download Select Important Safety Information

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