selecting glp-1 ra treatment...2017/06/07 · a recent national diabetes audit showed that 35.2% of...

Selecting GLP-1 RA Treatment

Dr Felicity Kaplan

March 2017

Objectives

• Review the progressive nature of type 2 diabetes

• Understand the need for timely treatment intensification

• Examine the place of GLP-1 receptor agonists (GLP-1 RA) in guidelines

• Compare the attributes of different GLP-1 RA products available in the

UK

100

0

0

HbA1c

ß-cell function

Lifestyle Monotherapy Dual therapy

Insulin ±oral drugs for lowering blood glucose

Time (years)

8

>15

5

6

7

9

0

10

T2D=Type 2 diabetes mellitus.

Data from Heine RJ et al. BMJ. 2006; 333: 1200‒1204.

Progressively declining beta cell function in T2D

“waiting for failure”

New drug treatments in the last 10 years

GLP-1 RA

(once weekly)

Dulaglutide15

GLP-1 RA

(once weekly)

Albiglutide14

Biosimilar glargine11

Insulin + GLP-1 RA

fixed combination12

SGLT2-i + metformin

fixed combination13

2006 2007 2008 2009 2010 2011 2013 2012 2014 2015

SGLT2

Inhibitors

Dapagliflozin8

GLP-1 RA

(once weekly)

Exenatide QW7

DPP-4-i + metformin

fixed combination3

DPP-4-i

Sitagliptin4

GLP-1 RA

(once daily)

Lixisenatide10

Insulin

degludec 200

units/ml9

GLP-1 RA

(once daily)

Liraglutide6

Insulin

glargine 300

units/ml5

Insulin lispro

200 units/ml1

(renewal; first

authorisation 1996)

GLP-1 RA

(twice daily)

Exenatide

BID2

1. Humalog 200 units/ml Summary of Product Characteristics. 2. Byetta Summary of Product Characteristics. 3. Eucreas Summary of Product Characteristics. 4. Januvia Summary of Product

Characteristics. 5. Toujeo Summary of Product Characteristics. 6. Victoza Summary of Product Characteristics. 7. Bydureon Summary of Product Characteristics. 8. Forxiga Summary of Product

Characteristics. 9. Tresiba Summary of Product Characteristics. 10. Lyxumia Summary of Product Characteristics. 11. Abasaglar Summary of Product Characteristics. 12. Xultophy Summary of

Product Characteristics. 13. Xigduo Summary of Product Characteristics. 14. Eperzan Summary of Product Characteristics. 15. Trulicity Summary of Product Characteristics.

Date of Marketing Authorisation in the UK

Despite the addition of new treatment options, many

patients with type 2 diabetes are not meeting their treatment

goals

• Many patients are not meeting their outcome goals on oral therapy2,

increasing the risk of complications3

A recent national diabetes audit showed that

35.2% of patients with type 2 diabetes have

HbA1c >58mmol/mol (7.5%)1

1. Health & Social Care Information Centre (HSCIC). National Diabetes Audit ‒ 2012‒2013: Report 1, Care Processes and Treatment Targets. October 2014. Available at:

http://www.hscic.gov.uk/catalogue/PUB14970/nati-diab-audi-12-13-care-proc-rep.pdf [Last Accessed: December 2015]. 2. Casagrande S et al. Diabetes Care 2013; 36(8): 2271‒2279.

3. Inzucchi SE et al. Diabetes Care. 2015; 38: 140–149.

35.2%

The treatment intensification challenge

• How long do people with type 2 diabetes wait for therapy intensification

despite an HbA1c ≥58 mmol/mol (7.5%)?

• 50% of patients may be uncontrolled on oral therapy for an average of 5

years before moving onto an injectable2

1. Khunti K et al. Diabetes Care 2013; 36: 3411–3417. 2. Rubino A et al. Diabetic Medicine 2007; 24: 1412–1418.

HbA1c ≥58 mmol/mol (7.5%) Time to next intensification (median)1

On 1x OAD

On 2x OADs

1.9 years

7.2 years

The potential reward for improved control

Every 1% reduction in HbA1c REDUCED

RISK

Deaths from diabetes

Microvascular

complications

Amputation or death

from peripheral

vascular disorders

1%

43%

37%

Fatal or non-fatal MI

21%

14%

Data from Stratton IM et al. BMJ 2000; 321: 405‒412.

Delayed initiation of GLP-1 RAs in the UK – IMS localised data

The NICE guideline 28 recommends initiation of GLP-1 RA therapy in combination with metformin and sulphonylurea when

triple therapy with metformin and two other oral medications is not effective, or tolerated or contraindicated, fails to maintain

an HbA1c ≤58 mmol/mol (≤7.5%, or other higher level agreed with the patient) and the patient meets one of the following

criteria

• a BMI of 35 kg/m2 or higher (adjust accordingly for people from black, Asian and other minority ethnic groups) and specific

psychological or other medical problems associated with obesity or

• a BMI lower than 35 kg/m2 and for whom insulin therapy would have significant occupational implications or weight loss

would benefit other significant obesity-related comorbidities

1. National Institute for Health and Care Excellence. Type 2 diabetes in adults: management. NICE guideline 28. London: NICE; December 2015 (http://www.nice.org.uk/guidance/ng28) [Last

Accessed: January 2016]. 2. Data on File. IMS data May 2015, HbA1C level before starting GLP-1 Receptor Agonist Therapy. Eli Lilly and Company; 2015.

% P

atie

nts

at th

is le

ve

l b

efo

re

sta

rtin

g G

LP

-1 R

A T

he

rap

y*2

HbA1c (%)

3% 3%

9%

13% 12%

16%

11%

33%

0%

5%

10%

15%

20%

25%

30%

35%

<7.0 ≥7.0

<7.5

≥7.5

<8.0

≥8.0

<8.5

≥8.5

<9.0

≥9.0

<9.5

≥9.5

<10.0

≥10.0

*n=14,623

In the UK 72% of patients are initiated on a GLP-1 receptor agonist at an HbA1c of ≥8.5%2

• Challenges with insulin

selection and titration

• Burdensome patient

counselling requirements

• Avoidance of patient burden

• Concern over hypoglycaemic

risk (insulin-specific)

• Lifestyle and employment

restrictions

• Fear of hypoglycaemia

(insulin-specific)

• Anxiety about injecting

• Concern about weight gain

Attitudes toward the initiation of insulin may delay escalation to other

injectable therapies1

1. Korytkowski M. Int J Obes Relat Metab Disord. 2002; 26(Suppl3): S18‒24.

Clinicians People with type 2 diabetes

Why is there a delay in initiating injectable therapy?

Despite the potential for improved glycaemic control, many people with type 2 diabetes are

reluctant to start injectable therapy1

GLP-1 RAs offer the following benefits:

1. Garcia-Perez L et al. Diabetes Ther 2013; 4: 175–194. 2. Freeman JS. J Am Osteopath Assoc. 2011; 111(2 suppl 1): eS15-eS20. 3. Byetta Summary of Product Characteristics. 4. Victoza

Summary of Product Characteristics. 5. Bydureon Summary of Product Characteristics.

Development of GLP-1 RAs over time has allowed the option of less

frequent injections for patients

20063 20094 20115

Twice daily Once daily Once weekly

HbA1c reductions2 Low risk of hypoglycaemia2 Potential for weight loss2

Treatment intensification with GLP-1 RAs may be

an attractive option for people with type 2 diabetes

SU + TZD or DPP-4-i or

SGLT2-i or GLP-1 RA or insulin

TZD + SU or DPP-4-i or

SGLT2-i or GLP-1 RA or insulin

DPP-4-i or SU or TZD or SGLT2-i

or insulin

SGLT2-i + SU or TZD or insulin

GLP-1 RA + SU or TZD

or insulin

Insulin + TZD or DPP-4-i +

SGLT2-i or GLP-1 RA

Metformin +

3-drug

combinations

The guidelines highlight where GLP-1 RAs can be used in combination:

Strategy progression after 3 months of unsuccessful glycaemic control (HbA1c target)

ADA=American Diabetes Association; EASD=European Association for the Study of Diabetes; DPP-4-I=Dipeptidyl peptidae-4 inhibitor; SGLT2-I=Sodium-glucose transporter 2 inhibitor; GLP-1

RA=Glucagon-like peptide-1 receptor agonist; SU=Sulphonylurea; TZD=Thiazolidinedione.

Inzucchi SE et al. Diabetes Care 2015; 38: 140‒149.

Initial drug

monotherapy

Metformin (or SU if metformin

not tolerated)

Combination

injectable therapy

Metformin +

Basal insulin + mealtime

insulin or GLP-1 RA

2-drug

combinations

Metformin +

SU

TZD

DPP-4-i

SGLT2-i

GLP-1 RA

Insulin (usually basal)

ADA/EASD Joint Position Statement:

NICE NG28: algorithm for blood glucose lowering therapy in

adults with type 2 diabetes


Accessed: January 2016]. Reproduced with permission.

*Reduction in HbA1c

**Not licensed for weight loss

ADA, Standards of Medical Care in Diabetes, section 7. Approaches to Glycemic Treatment Diabetes Care 2015; 38(Suppl. 1): S41–S48.

Potential dual therapy options for people with type 2 diabetes are displayed. It is not

meant to denote any specific preference.

Additional selection criteria

Metformin +

SU TZD DPP-4-i SGLT2-i GLP-1 RA

Efficacy* High High intermediate intermediate High

Hypo risk Moderate Low Low Low Low

Weight** Gain Gain Neutral Loss Loss

Side effects Hypoglycaemia Oedema, HF Rare GU, dehydration GI

Cost Low Low High High High

Blood pressure PPG

Treatment attributes of various drug choices for type

2 diabetes

Dose Dosing

frequency

Change in

HbA1c

Change in

weight (kg)

Exenatide1 10 μg Twice daily − 0.8% − 2.8

Liraglutide2

1.2 mg Once daily

− 1.3% − 2.6

1.8 mg − 1.3% − 2.8

Lixisenatide3 20 μg Once daily − 0.8% − 3.0

Exenatide4 2 mg Once weekly − 1.5% − 2.3

Trulicity®5 1.5 mg Once weekly − 1.4% − 2.9

Albiglutide6 30 mg Once weekly − 0.9% − 1.2

1. DeFronzo RA et al. Diabetes Care 2005; 28: 1092‒1100. 2. Nauck M et al. Diabetes Care 2009; 32: 84‒90. 3. Rosenstock J et al. Diabetes Care 2013; 36: 2945‒2951. 4. Bergenstal RM et al.

Lancet 2010; 376: 431‒439. 5. Dungan KM et al. Lancet 2014; 384: 1349‒1357. 6. Ahrén B et al. Diabetes Care 2014; 37: 2141‒2148.

Different GLP-1 RAs as add-on to metformin–

data derived from clinical trials

GLP-1 RAs as part of triple therapy –

data derived from clinical trials

Dose Background therapy Change in HbA1c

Change in weight

(kg)

Exenatide BID1 10 μg Metformin + SU -0.8% -1.6 kg

Exenatide QW2,3 2 mg

Oral antihyperglycaemic drugs -1.3% -2.7 kg

Included patients treated with metformin, SU,

TZD alone or in combination -2.0% -4.1 kg

Liraglutide4

1.2 mg Metformin + TZD (rosiglitazone) -1.5% -1.0 kg

1.8 mg Metformin + TZD (rosiglitazone) -1.5% -2.0 kg

Metformin + glimepiride -1.3% -1.8%

Lixisenatide5 20 μg Metformin + SU -0.9% -1.8 kg

Trulicity®6 1.5 mg Metformin + SU -1.1% -1.9 kg

Metformin + TZD (pioglitazone) -1.5% -1.3 kg

Albiglutide7 30 mg Metformin + glimepiride -0.6% -0.4 kg

Metformin + SU -0.7% -1.1 kg

1. Kendall D et al. Diabetes Care 2005; 28: 1083–1091. 2. Buse J et al. Diabetes Care 2010; 33: 1255–1261. 3. Buse J et al. Lancet 2013: 381: 117–124. 4. Victoza Summary of Product

Characteristics. Novo Nordisk Ltd. 5. Rosenstock J et al. Journal of Diabetes and its complications 2014; 28: 386–392. 6. Trulicity Summary of Product Characteristics. 7. Eperzan Summary of

Product Characteristics.

Indication in type 2 diabetes

Guidance on use

In renal

impairment In the elderly + insulin

Exenatide

BID1

In combination with: metformin, SU, TZD or metformin

+ SU, metformin + TZD in adults who have not

achieved adequate glycaemic control on maximally

tolerated doses of these oral therapies

Mild

Moderate (approach

dose

escalation

conservatively)

Use with caution

also indicated as

adjunctive therapy to

basal insulin +/- metformin

and/or pioglitazone in

adults who have not

achieved adequate

glycaemic control with

these agents

Exenatide

QW2

In combination with: metformin, SU, TZD or metformin

+ SU, metformin + TZD in adults who have not

achieved adequate glycaemic control on maximally

tolerated doses of these oral therapies

Mild only

No dose adjustment

required; consideration

to renal function with

older age

Not reported

Liraglutide3

To achieve glycaemic control as:

Monotherapy when diet and exercise alone do not

provide adequate glycaemic control in patients for

whom use of metformin is considered inappropriate

due to intolerance or contraindications

Combination therapy

In combination with oral glucose-lowering medicinal

products and/or basal insulin when these, together

with diet and exercise, do not provide adequate

glycaemic control (see sections 4.4 and 5.1 for

available data on the different combinations)

Mild-

moderate

No dose adjustment

required

Can be used in

combination with basal

insulin

Lixisenatide4

To achieve glycaemic control in combination with oral

glucose-lowering medicinal products and/or basal

insulin when these, together with diet and exercise, do

not provide adequate glycaemic control

Mild-

moderate

No dose adjustment

required

Can be used in

combination with basal

insulin

1. Byetta Summary of Product Characteristics. 2. Bydureon Summary of Product Characteristics. 3. Victoza Summary of Product Characteristics. 4. Lyxumia Summary of Product Characteristics.

Different GLP-1 RAs: licensed indications and

special populations

Indication in type 2 diabetes

Guidance on use

In renal

impairment In the elderly + insulin

Trulicity®1

To improve glycaemic control as:



whom the use of metformin is considered

inappropriate due to intolerance or contraindications

Add-on therapy in combination with other glucose-

lowering medicinal products including insulin, when

these, together with diet and exercise, do not provide

adequate glycaemic control

Mild-

moderate

No dose adjustment

required; ≥75 years

consider 0.75 mg dose

Can be used in

combination with insulin

Albiglutide2

To improve glycaemic control as:



whom use of metformin is considered inappropriate

due to contraindications or intolerance

Add-on combination therapy in combination with

other glucose-lowering medicinal products including

basal insulin, when these, together with diet and

exercise, do not provide adequate glycaemic control

Mild-

moderate

No dose adjustment

required

Can be used in

combination with insulin

1. Trulicity Summary of Product Characteristics. 2. Eperzan Summary of Product Characteristics.

Different GLP-1 RAs: licensed indications and

special populations

a: 60 minutes before 2 main meals (6 hours apart)

b: any time of day, independent of meals

1. Byetta Summary of Product Characteristics. 2. About the Byetta pen. Available at: https://www.byetta.com/getting-started-on-byetta/about-the-byetta-pen. [Last accessed: April 2016]. 3. Victoza Summary of

Product Characteristics. 4. Lyxumia Summary of Product Characteristics. 5. Bydureon Summary of Product Characteristics. 6. Bydureon Frequently Asked Questions. Available at:

https://www.bydureon.com/using-bydureon/bydureon-faqs.html. [Last accessed: April 2016]. 7. Trulicity Summary of Product Characteristics. 8. Eperzan Summary of Product Characteristics. 9. European

Medicines Agency. Eperzan Assessment Report. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/002735/WC500165119.pdf. [Last accessed:

April 2016].

Dose Need to

reconstitute

Needle

included

Hidden

needle

Needle

gauge

Exenatide BIDa,1,2 10μg NO ✗ ✗ 29, 30 or

31

Liraglutide QoDb,3 1.2mg

NO ✗ ✗ 32

Liraglutide QoDb,3 1.8mg

Lixisenatide QoDb,4 20μg NO ✗ ✗ 29 to 32

Exenatide QWb,5,6 2 mg YES ✔ ✗ 23

Trulicity® QWb,7 1.5 mg NO ✔ ✔ 29

Albiglutide QWb,8,9 30mg YES ✔ ✗ 29

Different GLP-1 RAs, different devices and practical

considerations

Dulaglutide offers significant HbA1c reduction in a

ready-to-use pen with once-weekly dosing1

Trulicity is indicated in adults with type 2 diabetes mellitus to

improve glycaemic control as:

Monotherapy 0.75 mg once weekly

When diet and exercise alone do not provide adequate

glycaemic control in patients for whom the use of metformin is

considered inappropriate due to intolerance or contraindications.

Add-on therapy 1.5 mg once weekly

In combination with other glucose-lowering medicinal products

including insulin, when these, together with diet and exercise, do

not provide adequate glycaemic control. For potentially

vulnerable populations, such as patients ≥ 75 years, 0.75 mg

once weekly can be considered as a starting dose

Trulicity 1.5 mg demonstrated statistically superior HbA1c reduction in phase III clinical trials vs metformin,

exenatide BID, insulin glargine, and sitagliptin. Trulicity 1.5mg demonstrated statistically noninferior HbA1c reduction

vs liraglutide 1.8 mg in 1 phase III trial.

1. Trulicity Summary of Product Characteristics

In a post-hoc analysis of patients from Award 1, Trulicity achieved

HbA1c reductions >2% in the subgroup of patients with a baseline

HbA1c ≥8.5%1

In the UK 72% of patients are initiated on a GLP-1 receptor agonist at an HbA1c of ≥8.5%*2

*Patients had their HbA1c recorded in the 6 months prior to initiation of GLP-1 therapy

1. Bain S et al. Poster presented at the PCDS 2015; 5–6 November, Birmingham 2. Data on File. IMS data May 2015, HbA1C level before starting GLP-1 Receptor Agonist Therapy. Eli Lilly and

Company; 2015.

HbA1c reduction

Trulicity 1.5 mg

(n=191; baseline 7.4% [57.4 mmol/mol])

Exenatide BID


Placebo


Trulicity 1.5 mg


Exenatide BID


Placebo


†P≤0.001 vs placebo

‡P<0.001 vs exenatide

Comparisons are

within each baseline

HbA1c cohort

-1.16%

-0.17%

-0.64%

0

-1.6

-1.2

-0.8

-0.4

-2.0

<8.5% (69.4 mmol/mol)

-2.4

†‡

†

-1.86%

-0.76%

0

-1.6

-1.2

-0.8

-0.4

-2.0

≥8.5% (69.4 mmol/mol)

-2.4 †‡ -2.37%

Hb

A1c c

han

ge f

rom

baselin

e ±

SE

(%

, L

S m

ean

)

Hb

A1c c

han

ge f

rom

baselin

e ±

SE

(%

, L

S m

ean

) H

bA

1c c

han

ge fro

m b

aselin

e ±

SE

(mm

ol/m

ol, L

S m

ean

)

0

-08

-06

-04

-02

-24

-26

-10

-12

-14

-16

-18

-20

-22

Hb

A1c c

han

ge fro

m b

aselin

e ±

SE

(mm

ol/m

ol, L

S m

ean

)

0

-08

-06

-04

-02

-24

-26

-10

-12

-14

-16

-18

-20

-22

Hypoglycaemia with Trulicity 1.5 mg

Please be aware: Patients receiving Trulicity in combination with a sulphonylurea or prandial insulin may have an

increased risk of hypoglycaemia. The risk may be lowered by reducing the dose of sulphonylurea or insulin.1

*Documented symptomatic hypoglycaemia and blood glucose 3.9 mmol/L.1

0

0.2 Rate

of sym

pto

ma

tic h

yp

og

lyca

em

ia (

ep

iso

de

s/p

atien

t/ye

ar)

1.67

3.02

0.12 0.29

AWARD-6 Without background sulphonylurea

Add-on to metformin

AWARD-2 With background sulphonylurea

Add-on to metformin and a sulphonylurea

Rates of documented symptomatic hypoglycaemia*

1.8

1.0

1.2

1.4

1.6

0.6

0.8

0.4

2

2.2

2.4

2.6

2.8

3

3.2

0.19

0.75

AWARD-1 Add-on to metformin

and pioglitazone

Trulicity 1.5 mg (n=273)

Insulin glargine (n=262)


Liraglutide (n=300)


Exenatide BID (n=276)

Trulicity Summary of Product Characteristics.

Incidence of nausea was comparable with Trulicity

1.5 mg and liraglutide 1.8 mg in a head-to-head trial1

Pa

tie

nts

(%

)

50

10

20

30

40

0 0 2 8 12 20 26 1

Time (weeks)

4

Trulicity 1.5 mg

(n=299)

Liraglutide

0.6 mg 1.2 mg

1.8 mg titrated over

the first 3 weeks of

treatment (n=300)

1. Dungan KM et al. Lancet. 2014; 384(9951): 1349‒1357.

Pancreatic safety

The recommended dose for Trulicity is 1.5 mg when prescribed as add-on therapy. In AWARD-1, AWARD-2, AWARD-4 and AWARD-5, additional groups

received Trulicity 0.75 mg, which is the recommended dose for monotherapy or can be considered as a starting dose in potentially vulnerable populations such as

patients ≥75 years of age.


Acute pancreatitis

• Use of GLP-1 associated with a risk of pancreatitis

• Pancreatitis has been reported with Trulicity. The incidence of acute

pancreatitis in phase 2 and 3 clinical studies was 0.07% for Trulicity

compared to 0.14% for placebo and 0.19% for comparators with or

without additional background antidiabetic therapy

*Needles included in list price

**Cost refers to the maintenance dose of 20 micrograms once daily5

All figures have been rounded to 2 decimal places

1. Liraglutide MIMS. Available at: http://www.mims.co.uk/drugs/diabetes/oral-and-parenteral-hypoglycaemics/victoza. [Last Accessed: February 2016]. 2. Exenatide QW MIMS. Available at:

http://www.mims.co.uk/drugs/diabetes/oral-and-parenteral-hypoglycaemics/bydureon. [Last Accessed: February 2016]. 3. Albiglutide MIMS. Available at: http://www.mims.co.uk/drugs/diabetes/oral-

and-parenteral-hypoglycaemics/eperzan. [Last Accessed: February 2016]. 4. Exenatide BD MIMS. Available at: http://www.mims.co.uk/drugs/diabetes/oral-and-parenteral-hypoglycaemics/byetta.

[Last Accessed: February 2016]. 5. Lixisenatide MIMS. Available at: http://www.mims.co.uk/drugs/diabetes/oral-and-parenteral-hypoglycaemics/lyxumia. [Last Accessed: February 2016].

List price and cost per day of GLP-1 receptor

agonists

• We need to take a proactive approach in the management of glycaemic control in type 2

diabetes

• Despite the introduction of new therapies, clinical inertia results in many patients not

meeting their glycaemic goals

• GLP-1 RAs offer the potential for glycaemic control with a low risk of hypoglycaemia and

the potential for weight loss – NICE recommends after 3 oral agents1

• Choice of GLP-1 treatment should be based on:1

– the person's individual clinical circumstances, preferences and needs in addition to effectiveness

– safety, tolerability

– available licensed indications or combinations, and cost

– if 2 drugs in the same class are appropriate, choose the option with the lowest acquisition cost


Accessed: January 2016].

Summary

Dulaglutide has received positive opinion from the CHMP; however, there is no guarantee it will receive regulatory

approval and become commercially available in your affiliate.

UKDUA00278(2) December 2016

The latest update to the NICE type 2 diabetes guideline (NG28) now recommends that treatment choice should take individual needs into account1

• The choice of drug treatment should consider:

– the person's individual clinical circumstances, preferences and needs in addition to effectiveness

– safety, tolerability

– available licensed indications or combinations, and cost

– if 2 drugs in the same class are appropriate, choose the option with the lowest acquisition cost

NICE guideline 28 also updates and replaces the single technology appraisals for liraglutide (TA203) and exenatide (TA248)1

• Therefore there is no longer mandatory funding for liraglutide and exenatide once-weekly



NICE Guideline



Patient preference and needs The choice of drug treatment should consider the person’s

individual clinical circumstances, individual preferences and needs, safety,

cost (if 2 drugs in the same class are appropriate, choose the option with

the lowest acquisition cost), licensed indications or combinations available

in addition to effectiveness of the drug treatment(s) in terms of metabolic

response (NICE NG28)1

Both the Trulicity molecule and the pen were

designed with these patients in mind

The Patient Trulicity

Clinical profile

Has type 2 diabetes* and:

• currently on oral medications only

• HbA1c between 7.5% and 9.0%

• weight is a clinical concern

Efficacy evaluated in phase III clinical

trials in this patient population1‒7

Body weight change evaluated as

secondary endpoint1‒7

Lifestyle considerations

Wants to succeed, but:

• struggles to fit changes into a busy life

• disappointed about not reaching goals

An extended half-life for

once-weekly dosing1

Solubility to avoid the need

for reconstitution8,9

Needs to start an injectable therapy for

the first time, but like many patients is

reluctant to do so

Ready-to-use pen10

No need to see or touch needle10

Once-weekly dosing1

1. Trulicity Summary of Product Characteristics. 2. Wysham C et al. Diabetes Care. 2014; 37(8): 2159‒2167. 3. Giorgino F et al. Diabetes Care. 2015; 38: 2241‒2249. 4. Umpierrez G et al. Diabetes

Care. 2014; 37: 2168‒2176. 5. Blonde L et al. Lancet. 2015; 385: 2057‒2066. 6. Nauck M et al. Diabetes Care. 2014; 37(8): 2149‒2158. 7. Dungan KM et al. Lancet. 2014; 384(9951): 1349‒1357.

8. Barrington P et al. Diabetes Obesity and Metabolism 2011; 13: 426‒433. 9. Data on File. Wolfgang Glaesner interview. Eli Lilly and Company; 2014. 10. Trulicity Instructions for use.

*hypothetical patient

Patient-centred attributes: Results of the dulaglutide

molecular design1

• Once-weekly subcutaneous administration

• Soluble, ready-to-use formulation

• Reduced renal clearance

• Low potential for immunogenicity

1. Trulicity Summary of Product Characteristics.

GLP-1

analogue

Linker

Modified

IgG4-Fc

domain

Ready-to-use pen designed with the patient in mind

1. Trulicity Instructions for use. 2. Matfin G et al. J Diabetes Sci Technol. 2015; 9(5): 1071‒1079.

The Trulicity pen is ready-to-use1

• No reconstitution or priming required

• Pre-attached, hidden 29-gauge needle

• Each pen contains a fixed dose of Trulicity

Automatic dose delivery at the push of a button1

Administration that 99% of patients found easy2

Beta cells: Enhances

glucose-dependent

insulin secretion

GLP-1 secreted upon

the ingestion of food

Promotes satiety and

reduces appetite

Stomach:

Slows gastric emptying

Alpha cells:

Postprandial

glucagon secretion

1. Nauck MA et al. Diabetologia 1986; 29: 46‒52. 2. Drucker DJ. Diabetes 1998; 47: 159‒169. 3. Flint A et al. J Clin Invest 1998; 101: 515‒520. 4. Larsson H et al. Acta Physiol Scand 1997; 160:

413‒422. 5. Nauck MA et al. Diabetologia 1996; 39: 1546‒1553.

GLP-1 secreted upon

the ingestion of food

Liver:

Glucagon reduces

hepatic glucose output

GLP-1 effects in humans: Understanding the

glucoregulatory role of incretins1–5

Different GLP-1 RAs: safety

Very common (≥1 in 10) AEs

Exenatide BID1 • Hypoglycaemia (with metformin + SU/ with SU)

• Nausea, vomiting, diarrhoea

Exenatide QW2 • Hypoglycaemia (with SU)

• Nausea, diarrhoea

Liraglutide3 • Nausea, diarrhoea

Lixisenatide4 • Hypoglycaemia (with SU and/or basal insulin)

• Headache

• Nausea, vomiting, diarrhoea

Trulicity®5 • Hypoglycaemia (with insulin, glimepiride, metformin or metformin + glimepiride)

• Nausea, vomiting, diarrhoea, abdominal pain

Albiglutide6 • Hypoglycaemia (when used in combination with insulin or sulphonylurea)

• Diarrhoea, nausea

• Injection site reactions

1. Byetta Summary of Product Characteristics. 2. Bydureon Summary of Product Characteristics. 3. Victoza Summary of Product Characteristics. 4. Lyxumia Summary of Product Characteristics. 5. Trulicity

Summary of Product Characteristics. 6. Eperzan Summary of Product Characteristics.

Significant HbA1c reduction across 6 clinical trials


The recommended dose for Trulicity is 1.5 mg when prescribed as add-on therapy. In AWARD-1, AWARD-2, AWARD-4 and AWARD-5, additional

groups received Trulicity 0.75 mg, which is the recommended dose for monotherapy or can be considered as a starting dose in potentially vulnerable

populations such as patients ≥75 years of age.

HbA

1c c

hange fro

m b

aselin

e ±

SE

(%

, LS

mean)

0

-0.2

-0.4

-0.6

-0.8

-1.0

-1.2

-1.4

-1.6

-1.8

Monotherapy

-1.10%*

-0.56% -0.71%*

-0.39%

-1.36%

-1.51%*

-0.99%

0.46%

-1.08%*

-0.63%

-1.64%*

-1.41%

Trulicity 0.75 mg (n=270; baseline 7.58%

[59.3 mmol/mol])

Metformin (n=268; baseline 7.60%

[59.6 mmol/mol])


[65.3 mmol/mol])

Sitagliptin (n=315; baseline 8.09%

[64.9 mmol/mol])


[64.6 mmol/mol])

Liraglutide 1.8 mg (n=300; baseline 8.05%

[64.5 mmol/mol])


[65.0 mmol/mol])

Exenatide BID (n=276; baseline 8.07%

[64.7 mmol/mol])

Placebo (n=141; baseline 8.06%

[64.6 mmol/mol])


[65.9 mmol/mol])

Insulin glargine (n=262; baseline 8.10%

[65.0 mmol/mol])


[69.0 mmol/mol])

Insulin glargine (n=296; baseline 8.53%

[69.7 mmol/mol])

AWARD-3

(26 weeks)

Dual therapy

AWARD-5

(52 weeks)

Triple therapy

AWARD-1

(26 weeks)

Insulin

AWARD-4

(26 weeks)

AWARD-6

(26 weeks)

AWARD-2

(52 weeks)

HbA

1c c

hange fro

m b

aselin

e ±

SE

(mm

ol/m

ol, L

S m

ean)

0

-2

-4

-6

-8

-10

-12

-14

-16

-18

-2.0

-1.42%†

*P<.025 , superiority vs active comparator

†P<.001, noninferiority vs active comparator

Indicates likely first

injectable options

Weight change with Trulicity across phase III clinical trials


Trulicity is not indicated for weight loss; weight change was a secondary endpoint in clinical trials. The recommended dose for Trulicity is 1.5 mg when prescribed as add-on therapy. In AWARD-1, AWARD-2, AWARD-4 and AWARD-5, additional

groups received Trulicity 0.75 mg, which is the recommended dose for monotherapy or can be considered as a starting dose in potentially

vulnerable populations such as patients ≥75 years of age.

Change in b

ody

weig

ht

(kg)

3.0

2.0

1.0

0

-1.0

-2.0

-3.0

-4.0

-2.22

-1.36*

-3.03†

-1.53

-2.90*

-3.61

-1.30 -1.07

+1.24 +1.44

-1.87†

-0.87†

*P<.05 vs active comparator

†P<.001 vs active comparator

Trulicity 0.75 mg

(n=270)

Metformin

(n=268)

Trulicity 1.5 mg

(n=304)

Sitagliptin

(n=315)

Trulicity 1.5 mg

(n=299)

Liraglutide 1.8 mg

(n=300)

Trulicity 1.5 mg

(n=279)

Exenatide BID

(n=276)

Placebo

(n=141)

Trulicity 1.5 mg

(n=273)

Insulin glargine

(n=262)

Trulicity 1.5 mg

(n=295)

Insulin glargine

(n=296)

Weight change at prespecified primary time-point

+2.33

Monotherapy

AWARD-3

(26 weeks)

Dual therapy

AWARD-5

(52 weeks)

Triple therapy

AWARD-1

(26 weeks)

Insulin

AWARD-4

(26 weeks)

AWARD-6

(26 weeks)

AWARD-2

(52 weeks)

Indicates likely first

injectable options

HbA1c reduction with Trulicity 1.5 mg once-weekly was

noninferior to liraglutide 1.8 mg once daily in a head-to-head

trial1,2

Data presented are mean values at 26 weeks.

LS = least squares; SE = standard error.

1. Trulicity Summary of Product Characteristics. 2. Dungan KM et al. Lancet. 2014; 384(9951): 1349‒1357.

Trulicity 1.5 mg

(n=299; baseline

HbA1c: 8.1% [65.0

mmol/mol])

HbA

1c C

ha

nge

fro

m B

ase

line ±

SE

(%

, L

S M

ea

n)

-0.8

-0.6

-0.4

-0.2

-1.2

0

-1.6

-1.4

-1.0

-1.36% -1.42%

HbA

1c C

ha

nge

from

Ba

se

line ±

SE

(mm

ol/m

ol, L

S M

ea

n)

-16

-14

-12

-10

-8

-6

-4

-2

0

P<.0001

Non-inferiority vs liraglutide

-18

-1.8 -20

Liraglutide 1.8 mg

(n=300; baseline

HbA1c: 8.1% [65.0

mmol/mol])

selecting glp-1 ra treatment...2017/06/07 · a recent national diabetes audit showed that 35.2% of...

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