bydureon ® educate by expert toolkit scientific slides: bydureon clinical data developed with the...

Bydureon® Educate By Expert toolkit

Scientific slides: Bydureon clinical data

ENDORS

E

DDeveloped with the guidance and approval of an independent international editorial committee

Date of preparation: Apri l 2014 150515

Content guide

• These decks comprise a number of slides, arranged in story order. You may find that some slides are not relevant to your audience. Please hide these as you feel necessary

• Some slides are accompanied by a short sound bite video of an expert that you may wish to embed from the toolkit. These are marked with the ‘expert sound bite’ symbol

• All graphs have been created in PowerPoint to enable easy amends and translation

• HbA1c values and appropriate graphs include both DCCT (%) and IFFC (mmol/mol) units. Please delete where not appropriate for your market

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Expert sound bite

DCCT, Diabetes Control and Complications Trial; IFFC, International Federation of Clinical Chemistry and Laboratory Medicine.

Executive summary

• This slide deck covers the following topics and contains speaker notes to assist presentation:1. Introduction to Bydureon, microsphere technology and the steady-state principle

2. Overview of the Bydureon clinical trial programme (DURATION studies)

3. Data from the Bydureon DURATION-1, -2 and -3 studies• Overview

• Detailed data from long-term extension studies

4. Cardiovascular data from Bydureon studies

5. Bydureon safety and tolerability

6. Dosing, administration and tips for initiating patients on Bydureon

Introduction to Bydureon

When Bydureon is added to SU therapy, a reduction in the dose of SU should be considered to reduce the risk of hypoglycaemia.GLP-1, glucagon-like peptide-1; SU, sulphonylurea; TZD, thiazolidinedione.Bydureon. Summary of product characteristics.

About Bydureon

• Bydureon is a GLP-1 receptor agonist, and the first once-weekly treatment for Type 2 diabetes

– EU marketing authorisation received in June 2006

• Bydureon provides continuous glycaemic control in a single weekly injection

• Bydureon is indicated for the treatment of Type 2 diabetes in combination with:

• Metformin

• SU

• TZD

• Metformin + SU

• Metformin + TZD

Formulating exenatide into a long-release formulation

• Placeholder for video 1Di. Dr Orville Kolterman: Formulating exenatide into a long-release formulation

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Expert sound bite

Bydureon’s patented microsphere technology enables once-weekly dosing

• Proven microsphere technology provides a continuous level of exenatide1

– Microspheres consist of a biodegradable polymer that dissipates into CO2 and water1

– The technology is also used in other extended-release products such as risperidone and naltrexone2,3

Further degradation and metabolism of microsphere polymer provide sustained

level of exenatide1

Microsphere degradation and continued release of

exenatide1

Individual microspheres aggregate and initial release of exenatide1

Subcutaneous injection of microsphere suspension of

exenatide1

Slide is animated

CO2,, carbon dioxide.1. DeYoung MB, et al. Diabetes Technol Ther 2011;13:1145–54; 2. Risperdal Consta. Summary of product characteristics; 3. Vivitrol. Prescribing information.

Bydureon microsphere technology

• Placeholder for microsphere technology video

The microsphere technology

• Placeholder for video 1Dii. Dr Orville Kolterman: The microsphere technology

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Expert sound bite

Steady-state exenatide concentrations provide continuous glycaemic control with a single weekly injection

• With once-weekly injections of Bydureon, therapeutic concentrations of exenatide are reached in 2 weeks1,2

• Steady state is reached by 6–7 weeks1,2

– At steady state, there are minimal peak-to-trough fluctuations in exenatide levels

Figure adapted from Kim D, et al.2

1. Bydureon. Summary of product characteristics; 2. Kim D, et al. Diabetes Care 2007;30:1486–93.

Time (weeks)

450

400

350

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Steady state is maintained with subsequent weekly doses

Steady state achieved for continuous glycaemic control

Slide is animated

Weekly Bydureon injection

Bydureon clinical trial programme

Core design of DURATION trials

• DURATION: Diabetes Therapy Utilisation: Researching Changes in A1c, Weight, and Other Factors Through Intervention with Exenatide Once Weekly

• Primary endpoint: Change in HbA1c from baseline to endpoint1–6

• Secondary endpoints: Change in bodyweight, blood pressure, CV risk markers, and safety and tolerability from baseline to endpoint1–6

CV, cardiovascular.1. Drucker DJ, et al. Lancet 2008;372:1240–50; 2. Bergenstal RM, et al. Lancet 2010:376:431–9; 3. Diamant M, et al. Lancet 2010:375;2234–43; 4. Russell-Jones D, et al. Diabetes Care 2012;35:252–8; 5. Blevins T, et al. J Clin Endocrinol Metab 2011;96:1301–10; 6. Buse JB, et al. Lancet 2013;381:117–24.

Patients with:Type 2 diabetesHbA1c 7.1–11.0%

(54.1–96.7 mmol/mol)

Optional Bydureon extension

Bydureon 2 mg

Active comparator agent(s)

24–30 weeks

Bydureon is not indicated in Europe as first-line monotherapy in patients uncontrolled on diet and exercise alone. 7

When Bydureon is added to SU therapy, a reduction in the dose of SU should be considered to reduce the risk of hypoglycaemia.BID, twice daily; MET, metformin; PIO, pioglitazone; QD, daily; SITA, sitagliptin; SU, sulphoylurea; TZD, thiazolidinediones.1. Drucker DJ, et al. Lancet 2008;372:1240–50; 2. Bergenstal RM, et al. Lancet 2010:376:431–9; 3. Diamant M, et al. Lancet 2010:375;2234–43; 4. Russell-Jones D, et al. Diabetes Care 2012;35:252–8; 5. Blevins T, et al. J Clin Endocrinol Metab 2011;96:1301–10; 6. Buse JB, et al. Lancet 2013;381:117–24; 7. Bydureon. Summary of product characteristics.

Overview of DURATION trials

Trial Comparator Background Subjects In EU label

DURATION-11 Exenatide BIDOpen label

Drug naïve, MET, SU, TZD, or two of these agents

295

DURATION-22 SITA (100 mg QD) or PIO (45 mg QD)Double-blind

MET 491

DURATION-33 Insulin glargineOpen label

MET ± SU 456

DURATION-44 MET (2000 mg QD) or PIO (45 mg QD) or

SITA (100 mg QD)Double-blind

Drug naïve 820

DURATION-55 Exenatide BIDOpen label

Drug naïve, mono and combo failures

252

DURATION-66 Liraglutide (1.8 mg)Open label

Mono and combo failures

911

Slide is animated

Overview of DURATION-1, -2 and -3

Reduced HbA1c with Bydureon at the DURATION-1, -2 and -3 trials’ primary analysis

Figure adapted from Drucker DJ, et al. 2008,1 Bergenstal RM, et al. 2010,2 and Diamant M, et al. 2010.3

N-values represent ITT population. *p=0.0023 versus exenatide BID; †p<0.05 versus both comparators; ‡p=0.02 versus insulin glargine.BL, baseline; BID, twice daily; ITT, intent-to-treat; QD, daily.1. Drucker DJ, et al. Lancet 2008;372:1240–50; 2. Bergenstal RM, et al. Lancet 2010;376:431–39; 3. Diamant M, et al. Lancet 2010;375:2234–43.

DURATION-11

30 weeks (N=295)DURATION-22

26 weeks (N=491)

–2.0

–1.5

–1.0

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DURATION-33

26 weeks (N=456)

–1.5%(–16.4

mmol/mol)

ExenatideBID

BL=8.3%(67.2

mmol/mol)

Bydureon

–1.5%†

(–16.4 mmol/mol)

BL=8.6%(70.5

mmol/mol)

–0.9%(–9.8

mmol/mol)

Sitagliptin100 mg QD

BL=8.5%(69.4

mmol/mol)

–1.9%*(–20.8

mmol/mol)

Bydureon

BL=8.3%(67.2

mmol/mol)

–1.2%(–13.1

mmol/mol)

Pioglitazone45 mg QD

BL=8.5%(69.4

mmol/mol)

–1.5%‡

(–16.4 mmol/mol)

Bydureon

BL=8.3%(67.2

mmol/mol)

–1.3%(–14.2

mmol/mol)

Insulinglargine

BL=8.3%(67.2

mmol/mol)

–20

–15

–10

–5

0 Ch

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1c from

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se

line

(mm

ol/m

ol)

Reduced HbA1c with Bydureon sustained throughout the DURATION-1, -2 and -3 trials’ extension studies

Figure adapted from MacConell L, et al. 2013,1 Wysham C, et al. 2011,2 and Trautmann M, 2013.3

N-values represent number of patients entering the extension study. *p=0.03 versus insulin glargine.BL, baseline; BID, twice daily; QD, daily.1. MacConell L, et al. Poster presented at EASD 2013. P-980; 2. Wysham C, et al. Diabet Med 2011;28:705–14; 3. Trautmann M. Presented at ADA 2013:67-OR.

DURATION-11

5 years (N=158)DURATION-22

52 weeks (N=364)

–2.0

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DURATION-33

3 years (N=390)

Bydureon

–1.6%(–17.5

mmol/mol)

–1.4%(–16.3

mmol/mol)

Sitagliptin100 mg QD Bydureon

–1.6%(–17.5

mmol/mol)

Bydureon(pooled population)

Pioglitazone45 mg QD Bydureon

–1.0%*(–10.9

mmol/mol)

Bydureon

–0.8%(–8.7

mmol/mol)

Insulinglargine

BL=8.6%(70.5

mmol/mol)

BL=8.5%(69.4

mmol/mol)

BL=8.2%(66.1

mmol/mol)

BL=8.5%(69.4

mmol/mol)

BL=8.3%(67.2

mmol/mol)

BL=8.3%(67.2

mmol/mol)

–1.6%(–17.5

mmol/mol)

–20

–15

–10

–5

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(mm

ol/m

ol)

Reduced weight with Bydureon at the DURATION-1, -2 and -3 trials’ primary analysis

Figure adapted from Drucker DJ, et al. 2008,1 Bergenstal RM, et al. 2010,2 and Diamant M, et al. 2010.3

*p=0.89 versus exenatide BID; †p=0.0002 versus sitagliptin; ‡p<0.0001 versus pioglitazone; §p<0.0001 versus insulin glargine.Bydureon is not indicated for the treatment of obesity and weight change was a secondary endpoint in clinical trials. 4 BL, baseline; BID, twice daily; QD, daily.1. Drucker DJ, et al. Lancet 2008;372:1240–50; 2. Bergenstal RM, et al. Lancet 2010;376:431–39; 3. Diamant M, et al. Lancet 2010;375:2234–43; 4. Bydureon. Summary of product characteristics.

Bydureon

DURATION-11


26 weeks (N=491)

–4

–2

0

2

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DURATION-33

26 weeks (N=456)

ExenatideBID

Sitagliptin100 mg QDBydureon


Insulinglargine

–3.6 kg*

BL=102 kg

–2.3 kg†‡

BL=90 kg

–0.8 kg

BL=88 kg

–3.7 kg

BL=102 kg

+2.8

BL=86 kg

–2.6 kg§

BL=91.2 kg

+1.4 kg

BL=90.6 kg

Reduced weight with Bydureon sustained throughout the DURATION-1, -2 and -3 trials’ extension studies

Figure adapted from MacConell L, et al. 2013,1 Wysham C, et al. 2011,2 and Trautmann M, 2013.3

*p<0.001 vs baseline.Bydureon is not indicated for the treatment of obesity and weight change was a secondary endpoint in clinical trials. 4

BL, baseline; BID, twice daily; QD, daily.1. MacConell L, et al. Poster presented at EASD 2013. P-980; 2. Wysham C, et al. Diabet Med 2011;28:705–14; 3. Trautmann M. Presented at ADA 2013:67-OR;4. Bydureon. Summary of product characteristics.

Bydureon

DURATION-11

5 years (N=158)DURATION-22


3 years (N=390)

Sitagliptin100 mg QD Bydureon

Bydureon(pooled population)


BydureonInsulin

glargine

–4

–2

0

2

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kg

)

–1.8 kg

BL=90 kg

–1.9 kg

BL=88 kg

–2.8 kg

BL=100 kg

–0.2 kg

BL=86 kg

–2.5 kg*

BL=91.2 kg

+2.0 kg*

BL=90.6 kg

4

Benefits of Bydureon

• Placeholder for video 1Diii. Professor Kamlesh Khunti: Benefits of Bydureon

19

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Expert sound bite

DURATION-1

DURATION-1: Study details

When Bydureon is added to SU therapy, a reduction in the dose of SU should be considered to reduce the risk of hypoglycaemia.BID, twice daily; FPG, fasting plasma glucose; ITT, intent-to-treat; PPG, postprandial glucose; SU, sulphonylurea; TZD, thiazolidinedione.Drucker DJ, et al. Lancet 2008;372:1240–50.

DURATION-1: Primary endpoint

Study details N=295 (ITT population)Randomised, active-controlled, open-label, non-inferiority study

Study length 30 weeks

Background therapy None (as initial therapy) or treatment with metformin, a SU, a TZD or any combination of these agents

Comparator Exenatide BID

Primary endpoint HbA1c change from baseline at Week 30

Secondary endpoints Safety and tolerability; analysis of FPG, PPG, bodyweight, fasting glucagon, fasting lipids, blood pressure, exenatide pharmacokinetics, paracetamol absorption

Publication type Peer-reviewed publication

DURATION-1: Study details (continued)

DURATION-1: 52-week extension

Study details N=258 (entering open-ended assessment period)Randomised, active-controlled, open-label, non-inferiority study with a switch from comparator to Bydureon at Week 30

Study length 30 weeks with 22-week extension study (switch study)


Comparator Exenatide BID Bydureon at Week 30

Outcomes Glucose control during the transition from exenatide BID to Bydureon; safety and tolerability; efficacy of Bydureon at Week 52


When Bydureon is added to SU therapy, a reduction in the dose of SU should be considered to reduce the risk of hypoglycaemia.BID, twice daily; SU, sulphonylurea; TZD, thiazolidinedione.Buse JB, et al. Diabetes Care 2010;33:1255–61.


When Bydureon is added to SU therapy, a reduction in the dose of SU should be considered to reduce the risk of hypoglycaemia.BID, twice daily; FPG, fasting plasma glucose; SBP, systolic blood pressure; SU, sulphonylurea; TZD, thiazolidinedione.MacConell L, et al. Diabetes Metab Syndr Obes 2013;6:31–41

DURATION-1: 3-year extension

Study details N=258 (entering open-ended assessment period)Randomised, active-controlled, open-label, non-inferiority study with a switch from comparator to Bydureon at Week 30

Study length 3-year extension (switch study)



Study endpoints Change in HbA1c, FPG, weight, lipid profile and SBP



When Bydureon is added to SU therapy, a reduction in the dose of SU should be considered to reduce the risk of hypoglycaemia.BID, twice daily; FPG, fasting plasma glucose; SBP, systolic blood pressure; SU, sulphonylurea; TZD, thiazolidinedione.MacConell L, et al. Poster presented at EASD 2013. P-980.


Study details N=258 (entering open-ended assessment period; completer population n=158)Randomised, active-controlled, open-label, non-inferiority study with a switch from comparator to Bydureon at Week 30

Study length 5-year extension (switch study)



Study endpoints Change in HbA1c, FPG, weight, lipid profile and SBP

Publication type Congress abstract

DURATION-1: Reduced HbA1c with Bydureon versus exenatide BID over 1 year

• At 1 year, patients receiving Bydureon achieved HbA1c reductions of –2.0% (–21.9 mmol/mol), regardless of whether they started on Bydureon or switched to Bydureon at 30 weeks1

– 71% of all patients achieved HbA1c <7% with Bydureon, irrespective of treatment at initiation

Figure adapted from Buse JB, et al. 2010.1 *p<0.05 versus exenatide BID. BID, twice daily; BL, baseline; CI, confidence interval.1. Buse JB, et al. Diabetes Care 2010;33:1255–61; 2. MacConell L, et al. Presented at EASD 2013. Abstract 980.

Bydureon BL=8.3% (67.2 mmol/mol)

Exenatide BID Bydureon BL=8.2% (66.1 mmol/mol)

60 524844403633302622181410–2.5

–2.0

–1.5

–1.0

–0.5

0.0

Time (weeks)

Ch

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** * * * * * *

All subjects received Bydureon

–2.0% (21.9 mmol/mol)

–2.0%(21.9 mmol/mol)

Change from BL:

–25

–20

–15

–10

–5

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bA

1c (mm

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DURATION-1: Reduced HbA1c with Bydureon sustained over 5 years

• HbA1c reductions were sustained over 5 years with Bydureon (mean change in HbA1c from baseline –1.6% [95% CI, –1.8 to –1.3] [–17.5 mmol/mol])

• 44% of all patients achieved HbA1c <7% with Bydureon, irrespective of treatment at initiation

Figures adapted from Drucker DJ, et al. 2008,1 MacConell L, et al. 2013,2 and MacConell L, et al. 2013.3 BID, twice daily; BL, baseline; CI, confidence interval.1. Drucker DJ, et al. Lancet 2008;372:1240–50; 2. MacConell L, et al. Diabetes Metab Syndr Obes 2013; 6:31–41; 3. MacConell L, et al. Poster presented at EASD 2013. P-980.

5 years3

(n=158)3 years2

(n=194)30 weeks1

(n=148)

– 2.0

–1.5

–1.0

–0.5

0.0

Ch

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Hb

A1c

(%

)

–1.6%(17.5

mmol/mol)

–1.6%(–17.5

mmol/mol)

BL=8.2%(66.1

mmol/mol)

–1.6%(–17.5

mmol/mol)

BL=8.2%(66.1

mmol/mol)

–1.9%(–20.8

mmol/mol)

BL=8.3%(67.2

mmol/mol)

–20

–15

–10

–5

0 Ch

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bA

1c (mm

ol/m

ol)

Randomised to Bydureon (evaluable population)

Pooled population (all Bydureon completers)

DURATION-1: Weight reductions with Bydureon versus exenatide BID over 1 year

• Strong HbA1c reductions with Bydureon were accompanied by weight reductions of 4.1–4.5 kg at 1 year1

Figure adapted from Buse JB, et al. 2010.1 Bydureon is not indicated for the treatment of obesity and weight change was a secondary endpoint in clinical trials. 3

BID, twice daily; BL, baseline; CI, confidence interval.1. Buse JB, et al. Diabetes Care 2010;33:1255–61; 2. MacConell L, et al. Presented at EASD 2013. Abstract 980; 3. Bydureon. Summary of product characteristics.

60 5248444036302622181410–5

–4

–3

–2

–1

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Time (weeks)

Ch

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t (k

g)

All subjects received Bydureon

–4.1 kg

–4.5 kg

Change from BL:

BydureonBL=103 kg

Exenatide BID Bydureon BL=102 kg

DURATION-1: Weight reductions with Bydureon sustained over 5 years*

• Weight reductions with Bydureon were sustained over 5 years (mean reductions from baseline –2.8kg [95% CI, –4.3 to –1.2]

Figures adapted from Drucker DJ, et al. 2008,1 MacConell L, et al. 2013,2 and MacConell L, et al. 2013.3 *Bydureon is not indicated for the management of obesity and weight change was a secondary endpoint in clinical trials. 4

BID, twice daily; BL, baseline; CI, confidence interval.1. Drucker DJ, et al. Lancet 2008;372:1240–50; 2. MacConell L, et al. Diabetes Metab Syndr Obes 2013; 6:31–41; 3. MacConell L, et al. Poster presented at EASD 2013. P-980; 4. Bydureon. Summary of product characteristics.

5 years3

(n=158)3 years2

(n=194)30 weeks1

(n=148)

–4

–3

–2

–1

0

Ch

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dy

we

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t (k

g)

–1.6%(17.5

mmol/mol)

–2.3 kg

BL=101 kg

–2.8 kg

BL=100 kg

–4.0 kg

BL=102 kg

Randomised to Bydureon (evaluable population)

Pooled population (all Bydureon completers)

DURATION-2


CV, cardiovascular; FPG, fasting plasma glucose; HRQoL, health-related quality of life; IIT, intent-to-treat; SMBG, self-monitored blood glucose; QD, once daily.Bergenstal RM, et al. Lancet 2010;376:431–39.


Study details N=491 (ITT population)Randomised, double-blind, double-dummy, superiority trial


Background therapy Metformin

Comparators Sitagliptin 100 mg QDPioglitazone 45 mg QD

Primary endpoint Change in HbA1c from baseline at Week 26

Secondary endpoints Changes at Week 26 in: Proportion of patients achieving HbA1c ≤6.5% (≤47.5 mmol/mol) or ≤7.0% (≤53.0 mmol/mol); FPG; six-point SMBG profile; bodyweight; fasting lipid profile; fasting insulin profile; blood pressure; CV risk markers; patient-reported HRQoL; safety and tolerability



CV, cardiovascular; FPG, fasting plasma glucose; QD, once daily.Wysham C, et al. Diabet Med 2011;28:705–14.

DURATION-2: 52-week extension study

Study details N=364 (entering extension study)Randomised, double-blind, double-dummy, superiority trial

Study length 26 weeks with a 26-week extension (switch study)

Background therapy Metformin

Comparators Sitagliptin 100 mg QD Bydureon at Week 26Pioglitazone 45 mg QD Bydureon at Week 26

Outcomes Change from baseline at Weeks 26 and 52 and from Week 26 to Week 52 in: HbA1c; patients achieving HbA1c <7.0% (<53.0 mmol/mol) and ≤6.5% (≤47.5 mmol/mol); FPG; bodyweight; fasting lipids; fasting insulin, blood pressure; CV risk markers; safety and tolerability


DURATION-2: Reduced HbA1c with Bydureon versus sitagliptin and pioglitazone

• Significant HbA1c reductions with Bydureon were sustained over 1 year, regardless of initial therapy

Graph showing data for the evaluable population. *p<0.05 versus Week 26. BL, baseline.Wysham C, et al. Diabet Med 2011;28:705–14.

Bydureon, BL=8.6% (70.5 mmol/mol) Sitagliptin Bydureon, BL=8.5% (69.4 mmol/mol)Pioglitazone Bydureon, BL=8.5% (69.4 mmol/mol)

–0.31% (–0.50, –0.13)* (–3.4 mmol/mol)

Change from Week 26 to Week 52:

0.06% (–0.13, 0.25) (0.7 mmol/mol)

–0.10% (–0.29, 0.09) (–1.1 mmol/mol)

60 52464034302622181410–2.0

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–1.5

–1.0

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DURATION-2: Weight change* with Bydureon versus sitagliptin and pioglitazone

• Patients treated with Bydureon achieved significant weight reductions at 26 weeks*1

– Individuals who switched to Bydureon from sitagliptin or pioglitazone at the end of the blinded period experienced further weight reductions

Graph showing data for the evaluable population.*Bydureon is not indicated for the treatment of obesity and weight change was a secondary endpoint in clinical trials. 2 *p<0.05 versus Week 26. BL, baseline.1. Wysham C, et al. Diabet Med 2011;28:705–14; 2. Bydureon. Summary of product characteristics.

Blinded period

–1.1 kg (–1.8, –0.5)†

Change from Week 26:

0.7 kg (0.1, 1.4)†

–3.0 kg (–3.7, –2.3)†

60 52464034302622181410–3

–2

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2

3

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Time (weeks)

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Open-ended period

Bydureon, BL=90 kgSitagliptin Bydureon, BL=86 kgPioglitazone Bydureon, BL=86 kg

DURATION-3


When Bydureon is added to SU therapy, a reduction in the dose of SU should be considered to reduce the risk of hypoglycaemia.AAT, alanine aminotransferase; ACR, albumin-to-creatinine ratio; CRP, C-reactive protein; FPG, fasting plasma glucose; HOMA, homeostasis model assessment; SMBG, self-monitored blood glucose; SU, sulphonylurea. Diamant M, et al. Lancet 2010;375:2234–43.


Study details N=456 (ITT population)Open-label, randomised, parallel study


Background therapy Metformin ± SU

Comparator Insulin glargine (starting dose: 10 IU/day)

Primary endpoint Change in HbA1c from baseline at Week 26

Secondary endpoints Patients achieving HbA1c <7.0% (<53.0 mmol/mol) and ≤6.5% (≤47.5 mmol/mol); FPG; SMBG; bodyweight; fasting plasma lipids; urinary ACR; CRP; HOMA β-cell function and insulin sensitivity; AAT; 1,5-anhydroglucitol; safety and tolerability



When Bydureon is added to SU therapy, a reduction in the dose of SU should be considered to reduce the risk of hypoglycaemia.ACR, albumin-to-creatinine ratio; FPG, fasting plasma glucose; HOMA, homeostasis model assessment; SMBG, self-monitored blood glucose; SU, sulphonylurea; WHR, waist-to-hip ratio.Diamant M, et al. Diabetes Care 2012;35:683–9.

DURATION-3: Planned interim analysis (84 weeks)

Study details N=390 (entering extension study)Open-label, randomised, parallel study

Study length 26 weeks with interim analysis at 84 weeks


Comparator Insulin glargine (starting dose 10 IU/day; target glucose range, 4.0–5.5 mmol/L)

Key efficacy measure Change in HbA1c from baseline to study treatment endpoint

Secondary efficacy measures

Time to failure to maintain glycaemic control; patients achieving HbA1c <7.0% (<53.0 mmol/mol) and ≤6.5% (≤47.5 mmol/mol); bodyweight; FPG; SMBG, fasting serum lipids

Exploratory measures Urinary ACR; HOMA β-cell function; WHR; anti-exenatide antibody titre; safety and tolerability



When Bydureon is added to SU therapy, a reduction in the dose of SU should be considered to reduce the risk of hypoglycaemia.FPG, fasting plasma glucose; SU, sulphonylurea.Trautmann M. Presented at ADA 2013:67-OR.


Study details N=390 (entering extension study; completer population n=287)Open-label, randomised, parallel study

Study length 26 weeks with 3-year extension


Comparator Insulin glargine (target glucose range 4.0–5.5 mmol/L)

Outcomes HbA1c; bodyweight; patients achieving reductions in HbA1c and bodyweight; FPG; anti-exenatide antibody titre; safety and tolerability

Publication type Congress abstract

• Bydureon-treated patients experienced significantly greater HbA1c reductions at 84 weeks than those treated with insulin glargine

DURATION-3: Reduced HbA1c with Bydureon versus basal insulin at the 84-week interim analysis

Graph showing data for the intent-to-treat population. *p<0.05; †p=0.029. BL, baseline.Diamant M, et al. Diabetes Care 2012;35:683–9.

Bydureon, BL=8.3% (67.2 mmol/mol; n=233) Insulin glargine, BL=8.3% (67.2 mmol/mol; n=223)

–1.0 ± 0.1% (–10.9 mmol/mol)

–1.2 ± 0.1% (–13.1 mmol/mol)†

Change from BL:

84726048362622181480

0.56.0

7.0

8.0

Hb

A1c

(%

)

Time (weeks)

**********

5.5

45

65

Hb

A1c (m

mo

l/mo

l)

60

55

50

• Over 3 years, significantly greater reductions in HbA1c with Bydureon versus insulin glargine were sustained despite adherence to a treat-to-target insulin titration algorithm

DURATION-3: Reduced HbA1c with Bydureon versus basal insulin sustained over 3 years

–1.5

–1.0

–0.5

0.0

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A1c

fro

m

ba

se

lin

e (

%)

–1.0%*(–10.9

mmol/mol)

Bydureon

–0.8%(–8.7

mmol/mol)

Insulinglargine

BL=8.3%(67.2

mmol/mol)

BL=8.3%(67.2

mmol/mol)

–15

–10

–5

0

Ch

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bA

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ol)

Graph adpated from Trautmann M, 2013, showing data for the intent-to-treat population. *p=0.03. BL, baseline; SE, standard error.Trautmann M. Presented at ADA 2013:67-OR.

• Treatment with Bydureon resulted in significant weight loss instead of weight gain with insulin glargine at 84 weeks1

DURATION-3: Weight change with Bydureon versus basal insulin at the 84-week interim analysis

Graph showing data for the intent-to-treat population.1 *p<0.05; †p<0.001. BL, baseline; SE, standard error.Bydureon is not indicated for the treatment of obesity and weight change was s secondary endpoint in clinical trials. 2

1. Diamant M, et al. Diabetes Care 2012;35:683–9; 2. Bydureon. Summary of product characteristics.

Time (weeks)

*

+2.4 ± 0.2 kg

–2.1 ± 0.2 kg†

84726048362622181481

–4

–2

2

4

Ch

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bo

dy

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igh

t (k

g)

24

0

********

***

Bydureon, BL=91.2 kg (n=233)Insulin glargine, BL=90.6 kg (n=223)

Change from BL:

• Reductions in bodyweight were sustained over 3 years with Bydureon whilst patients in the insulin glargine group experienced significant weight gain*1

DURATION-3: Weight change* with Bydureon versus basal insulin sustained over 3 years

Graph adapted from Trautmann M, 2013,1 showing data for the intent-to-treat population.1 *p<0.001 vs BL. BL, baseline; SE, standard error.*Bydureon is not indicated for the treatment of obesity and weight change was s secondary endpoint in clinical trials. 2

1. Trautmann M. Presented at ADA 2013:67-OR; 2. Bydureon. Summary of product characteristics.

–3

–2

0

2

Ch

an

ge

in

Hb

A1c

fro

m

ba

se

lin

e (

%)

–2.49 kg*

Bydureon

+2.01 kg

Insulinglargine

BL=8.3%

BL=8.3%

–1

1

3

DURATION-3: Additional benefits of Bydureon

• At 3 years, twice as many Bydureon patients (68%) achieved reductions in both HbA1c and bodyweight compared with insulin glargine patients (34%)1

Graph adapted from Trautmann M, 2013.1

Bydureon is not indicated for the treatment of obesity and weight change was s secondary endpoint in clinical trials. 2

1. Trautmann M. Presented at ADA 2013:67-OR; 2. Bydureon. Summary of product characteristics.

Pa

tie

nts

ac

hie

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g r

ed

uc

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ns

in

H

bA

1c a

nd

bo

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we

igh

t (%

)

0

50

70

20

30

60

40

10

Bydureon

68%

Insulinglargine

34%

DURATION-3: Incidence of minor hypoglycaemia versus insulin glargine

• Bydureon was associated with a lower rate of minor hypoglycaemia than insulin glargine at 84 weeks1

– SUs are associated with a higher risk of hypoglycaemia; when Bydureon is added to SU therapy, a reduction in the dose of SU should be considered to reduce the risk of hypoglycaemia2

Graph adapted from Diamant et al. Diabetes Care 2012.1 *p<0.001.Minor hypoglycaemia was defined as patients reporting symptoms consistent with hypoglycaemia and plasma glucose concentration of <3.0 mmol/L. Three patients (one Bydureon + metformin, one insulin glargine + metformin and insulin glargine + metformin and SU) had an episode of hypoglycaemia requiring the assistance of another person, but not involving loss or severe impairment of consciousness.1 SU, sulphonylurea.1. Diamant M, et al. Diabetes Care 2012;35:683–9; 2. Bydureon. Summary of product characteristics.

Metformin background

Pa

tie

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re

po

rtin

g m

ino

r h

yp

og

lyc

ae

mia

(%

)

0

50

70

20

30

60

40

10

32%

n=51

Bydureon Insulin glargine

54%

n=36

Metformin + SU background

8%

n=13

*24%

n=17

*

Hypoglycaemia with GLP-1 receptor agonists

• Placeholder for video 1Div. Gwen Hall: Hypoglycaemia with GLP-1 receptor agonists

i

Expert sound bite

Change in CV markers with Bydureon

Evidence from DURATION-1

CV, cardiovascular.

Bydureon is associated with improvements in blood pressure

• In a pooled analysis of the six DURATION trials, significant improvements occurred in SBP and DBP from baseline with Bydureon treatment1

Bydureon is not indicated in Europe as first-line monotherapy in patients uncontrolled on diet and exercise alone. 2

CI, confidence interval; DBP, diastolic blood pressure; ITT, intent-to-treat; LS, least-squares; SBP, systolic blood pressure; SE, standard error.1. Grimm M, et al. Postgrad Med 2013;125:46–57; 2. Bydureon. Summary of product characteristics.

Population and parameterBaseline

(mean ± SE)Change from baseline

(LS mean ± SE)95% CI

SBP, mmHg

ITT population (n=1379) 130.5 ± 0.4 –2.8 ± 0.4 –3.5 to –2.1

SBP <130 mmHg at baseline (n=645) 118.8 ± 0.3 2.1 ± 0.5 1.2 to 3.1

SBP ≥130 mmHg at baseline (n=734) 140.8 ± 0.4 –7.2 ± 0.5 –8.3 to –6.2

DBP, mmHg

ITT population (n=1379) 79.2 ± 0.2 –0.8 ± 0.2 –1.2 to –0.4

DBP <80 mmHg at baseline (n=641) 72.0 ± 0.2 2.8 ± 0.3 2.2 to 3.4

DBP ≥80 mmHg at baseline (n=738) 85.5 ± 0.2 –3.7 ± 0.3 –4.3 to –3.1

DURATION-1: Changes in blood pressure over 5 years with Bydureon

• Over 5 years in the DURATION-1 study, improvements from baseline in blood pressure were seen with Bydureon treatment1–3

Figures adapted from Drucker DJ, et al. 2008,1 MacConell L, et al. 2013,2 and MacConell L, et al. 2013.3 *p<0.05 vs baseline.BP, blood pressure; DBP, diastolic blood pressure; SBP, systolic blood pressure.1. Drucker DJ, et al. Lancet 2008;372:1240–50; 2. MacConell L, et al. Diabetes Met Synd Obes 2013;6:31–41; 3. MacConell L, et al. Poster presented at EASD 2013. P-980.

Randomised to Bydureon(ITT population)Pooled population(completer population)

1

0

–1

–2

–3

–4

–5

Ch

an

ge

in

BP

(m

mH

g)

SBP

Week 301 Year 53

+0.6mmHg

–4.7mmHg

–2.1mmHg

–1.6mmHg

–1.7mmHg –2.0

mmHg*

Year 32

n=194

DBP

Week 301 Year 53Year 32

n=129Baseline 128 129 78 78129 78

• In the DURATION-1 5-year extension study, improvements from baseline in plasma lipids were observed with Bydureon treatment1–3

DURATION-1: Improvements in plasma lipids over 5 years with Bydureon

Figures adapted from Drucker DJ, et al. 2008,1 MacConell L, et al. 2013,2 and MacConell L, et al. 2013.3 *ITT population; †Completer population; ‡p<0.05 vs baseline.BL, baseline; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; NR, not reported; TG, triglycerides.1. Drucker DJ, et al. Lancet 2008;372:1240–50; 2. MacConell L, et al. Diabetes Met Synd Obes 2013;6:31–41; 3. MacConell L, et al. Poster presented at EASD 2013. P-980.

0.0

–0.1

–0.2

–0.3

–0.4

Ch

ang

e fr

om

B

L (

mm

ol/L

)

Total cholesterolWeek 30*1

(n=148)Year 5†3

(n=158)

–0.31mmol/L

–0.31mmol/L

–0.26‡

mmol/L

Year 3†2

(n=194)

B=4.49 B=4.5 B=4.6

0.1

0.0

–0.1

Ch

ang

e fr

om

B

L (

mm

ol/L

)

HDL-CWeek 30*1

(n=148)Year 5†3

(n=158)

+0.06mmol/L

–0.02mmol/L

+0.03mmol/L

Year 3†2

(n=194)

BL=1.14

BL=1.2 BL=1.2

0.1

0.0

–0.1

–0.2

–0.3

Ch

ang

e fr

om

B

L (

mm

ol/L

)

LDL-CWeek 30*1

(n=148)Year 5†3

(n=158)

–0.25mmol/L

–0.13mmol/L

–0.18‡ mmol/L

Year 3†2

(n=194)

B=2.37 B=2.5BL=2.4

0

–5

–10

–15C

han

ge

fro

m

BL

(%

)

TriglyceridesWeek 30*1

(n=148)Year 5†3

(n=158)

–13%

–15%

–12%‡

Year 3†2

(n=194)

BL=1.88 BL=1.7 BL=NR

Randomised to Bydureon(ITT population)

Pooled population(completer population)

Bydureon safety and tolerability

Bydureon is associated with a low incidence of hypoglycaemia

• In a post-hoc analysis of the DURATION clinical trial programme, Bydureon was shown to carry a low incidence of hypoglycaemia1

– Across all DURATION studies, no major hypoglycaemic events were reported

– Minor hypoglycaemia occurred primarily in patients using a concomitant SU

Concomitant SU use

Pa

tie

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ex

pe

rie

nc

ing

m

ino

r h

yp

og

lyc

ae

mia

(%

)

0

50

70

20

30

60

40

103%

n=918

16%n=461

No concomitant

SU useGraph adapted from Grimm et al. Postgrad Med 2013.1 Minor hypoglycaemia was defined as a report of symptoms consistent with hypoglycaemia and a concurrent blood glucose level <54 mg/dL (3 mmol/L), which resolved either independently or on self-treatment by the patient. Major hypoglycaemia was defined as an episode of symptoms resulting in loss of consciousness or seizure that promptly resolved on administration of glucose, or documented blood glucose level <54 mg/dL (3 mmol/L) requiring assistance from another person due to severe impairment in consciousness or behaviour.1

When Bydureon is added to SU therapy, a reduction in the dose of SU should be considered to reduce the risk of hypoglycaemia. 2

The DURATION-4 clinical trial of BYDUREON monotherapy vs metformin, sitagliptin or pioglitazone monotherapy was conducted in adult patients uncontrolled on diet and exercise alone. BYDUREON is not indicated as first-line monotherapy in patients uncontrolled on diet and exercise alone. 2

SU, sulphonylurea.1. Grimm M, et al. Postgrad Med 2013;125:47–57; 2. Bydureon. Summary of product characteristics.

Bydureon: Summary of safety and tolerability

• As with other GLP-1 receptor agonists, the most frequent adverse drug reactions (≥5% of patients treated with Bydureon) were mainly gastrointestinal-related (nausea, vomiting, diarrhoea and constipation)

• In addition, injection-site reactions (pruritus, nodules, erythema), hypoglycaemia (with a SU) and headache occurred

• Most adverse reactions associated with Bydureon were mild to moderate in intensity

• There have been rare, spontaneously reported events of acute pancreatitis. If pancreatitis is suspected, Bydureon should be discontinued

Data source comprises two placebo-controlled studies (10 and 15 weeks) and three studies of Bydureon versus exenatide BID (30-week study), sitagliptin and pioglitazone (26-week study) or insulin glargine (26-week study). Background therapies included diet and exercise, metformin, a SU, a TZD or a combination of oral antidiabetic agents. BID, twice daily; SU, sulphonylurea; TZD, thiazolidinedione.Bydureon. Summary of product characteristics.

System organ class/adverse reaction terms

Frequency of occurrence*

Very common (≥1/10) Common (≥1/100 to <1/10)

Metabolism and nutrition disorders Hypoglycaemia (with a SU)† Decreased appetite†

Nervous system disorders Headache† Dizziness†

Gastrointestinal disorders Nausea†

Vomiting† Diarrhoea† Constipation

Dyspepsia†

Abdominal pain†

Gastroesophageal reflux disease†

Abdominal distensionEructationFlatulence†

Skin and subcutaneous tissue disorders Hyperhidrosis‡

General disorders and administration site conditions

Injection-site pruritus Fatigue†

Injection-site erythemaInjection-site rashSomnolenceAsthenia‡

Feeling jittery‡

Very common and common adverse reactions reported with Bydureon in clinical trials and spontaneous reports

*Rate based on Bydureon clinical trial data (N=592 total; n=135 patients on SU); †Reactions were in the same frequency grouping in the exenatide BID group; ‡Rate based on exenatide twice daily clinical trial data; §Rate based on exenatide twice daily spontaneous reports data.Data source comprises two placebo-controlled studies (10 and 15 weeks) and three studies of Bydureon versus exenatide BID (30-week study), sitagliptin and pioglitazone (26-week study) or insulin glargine (26-week study). Background therapies included diet and exercise, metformin, a SU, a TZD or a combination of oral antidiabetic agents. When Bydureon is added to SU therapy, a reduction in the dose of SU should be considered to reduce the risk of hypoglycaemia.BID, twice daily; SU, sulphonylurea; TZD, thiazolidinedione.Bydureon. Summary of product characteristics.

*Rate based on Bydureon clinical trial data (N=592 total; n=135 patients on SU); †Rate based on Bydureon spontaneous reports data; ‡Rate based on exenatide twice daily clinical trial data; §Rate based on exenatide twice daily spontaneous reports data.Data source comprises two placebo-controlled studies (10 and 15 weeks) and three studies of Bydureon versus exenatide BID (30-week study), sitagliptin and pioglitazone (26-week study) or insulin glargine (26-week study). Background therapies included diet and exercise, metformin, a SU, a TZD or a combination of oral antidiabetic agents. BID, twice daily; SU, sulphonylurea; TZD, thiazolidinedione. Bydureon. Summary of product characteristics.

Uncommon, rare and very rare adverse reactions reported with Bydureon in clinical trials and spontaneous reports

System organ class/adverse reaction

terms

Frequency of occurrence

Uncommon (≥1/1000 to <1/100)

Rare (≥1/10,000 to <1/1000)

Very rare(<1/10,000)

Not known

Metabolism and nutrition disorders

Dehydration, generally associated with nausea, vomiting and/or diarrhoea§

Nervous system disorders Dysgeusia§

Gastrointestinal disorders Acute pancreatitis§

Immune system disorders Anaphylactic reaction†

Skin and subcutaneous tissue disorders

Pruritus and/or urticaria* Alopecia§ Macular and papular rash†

Angioneurotic oedema†

Renal and urinary disorders Altered renal function, including acute renal failure, worsened chronic renal failure, renal impairment, increased serum creatinine§

Investigations INR increased with concomitant warfarin use, some reports associated with bleeding§

Handling nausea that may occur with Bydureon treatment

• Nausea is a frequent side effect with all GLP-1 receptor agonists1–4

• <1% of patients discontinued Bydureon due to nausea1

• Most episodes of nausea were mild to moderate and decreased over time1,5

• In a 52-week trial, even when patients experienced nausea, it did not affect their reported level of treatment satisfaction with Bydureon6

Figure adapted from Maggs D, et al. 2012.5 GLP-1, glucagon-like peptide-1.1. Bydureon. Summary of product characteristics; 2. Byetta. Summary of product characteristics; 3. Victoza. Summary of product characteristics; 4. Lyxumia. Summary of product characteristics; 5. Maggs D, et al. Presented at ADA 2012. Presentation #4; 6. Best JH, et al. Diabet Med 2009;26:722–8.

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40

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180–212Weeks

Nausea with GLP-1 receptor agonists and effects on compliance

• Placeholder for video 1Dv. Professor Kamlesh Khunti: Nausea with GLP-1 receptor agonists and effects on compliance

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Expert sound bite

Handling injection-site reactions that may occur with Bydureon treatment

Injection-site reactions versus bumps

• Injection-site reactions associated with symptoms were categorised as adverse events (erythema, pruritus, rash)

• Occurred in 16% of patients in Phase III studies

• Mostly mild to moderate• Usually did not lead to withdrawal

from studies

Injection-site bumps

• Small, raised nodules that very frequently occur at the injection site– These are consistent with known

properties of poly (D,L-lactide co-glycolide) polymer microsphere technology

• Bumps are normally harmless and resolve over 4–8 weeks

Bydureon. Summary of product characteristics.

Size of bump

Bydureon injection-site bumps

• Placeholder for video 1Dvi. Professor Kamlesh Khunti: Bydureon injection-site bumps

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Expert sound bite

Contraindications and special warnings and precautions

ContraindicationsHypersensitivity to the active substance or to any of the excipients.

Warnings and precautionsNot to be used in patients with Type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis. Bydureon must not be administered by intravenous or intramuscular injection.

• Renal impairment Rare, spontaneously reported events of altered renal function with exenatide, including increased serum creatinine, renal impairment, worsened chronic renal failure and acute renal failure, sometimes requiring haemodialysis. Some occurred in patients experiencing events that may affect hydration and/or receiving medicinal products known to affect renal function/hydration status, including angiotensin converting enzyme inhibitors, angiotensin-II antagonists, non-steroidal anti-inflammatory medicinal products and diuretics. Reversibility observed with supportive treatment and discontinuation of potentially causative medicinal products, including exenatide.

No dose adjustment is necessary for patients with mild renal impairment (CrCL 50–80 ml/min). Clinical experience in patients with moderate renal impairment (CrCl 30–50 ml/min) is very limited. Bydureon is not recommended in these patients. Bydureon is not recommended for use in patients with end-stage renal disease or severe renal impairment (CrCL <30 ml/min).

• Severe gastrointestinal diseaseNot recommended.

CrCL, creatinine clearance.Bydureon. Summary of product characteristics.

Contraindications and special warnings and precautions (continued)

• Acute pancreatitisRare, spontaneously reported events of acute pancreatitis. Inform patients of the characteristic symptom of acute pancreatitis: persistent, severe abdominal pain. Resolution of pancreatitis has been observed with supportive treatment, but very rare cases of necrotising or haemorrhagic pancreatitis and/or death have been reported. If pancreatitis is suspected, discontinue use of Bydureon and other potentially suspect medicinal products. Do not resume Bydureon after pancreatitis has been diagnosed.

• Concomitant medicinal productsConcurrent use of Bydureon with insulin, meglitinides, alpha-glucosidase inhibitors, dipeptidyl peptidase-4 inhibitors or other GLP-1 receptor agonists have not been studied. The concurrent use of Bydureon and exenatide twice daily has not been studied and is not recommended.

• Weight lossRapid weight loss at a rate of >1.5 kg per week has been reported with exenatide, which may have harmful consequences.

• Discontinuation of treatmentThe effect of Bydureon may continue as plasma levels of exenatide decline over 10 weeks. Choice of other medicinal products and dose selection should be considered accordingly until exenatide levels decline.

GLP-1, glucagon-like peptide-1.Bydureon. Summary of product characteristics.

Drug interactions

The results of a study using paracetamol as a marker of gastric emptying suggest that the effect of Bydureon to slow gastric emptying is minor and not expected to cause clinically significant reductions in the rate and extent of absorption of concomitantly administered oral medicinal products. Therefore, no dose adjustment for medicinal products sensitive to delayed gastric emptying are required.

• Warfarin and cumarol derivativesA delay in tmax of about 2 h was observed when warfarin was administered 35 min after exenatide BID. No clinically relevant effects on Cmax or AUC were observed. Increased INR has been reported during concomitant use of warfarin and exenatide BID. INR should be monitored during initiation of Bydureon therapy in patients on warfarin and/or cumarol derivatives.

• HMG CoA reductase inhibitorsConcomitant use with exenatide was not associated with consistent changes in lipid profiles. Lipid profiles should be monitored as appropriate.

AUC, area under curve; BID, twice daily; INR, international normalised ratio.Bydureon. Summary of product characteristics.

Anti-exenatide antibodies

• Patients may develop antibodies to exenatide following treatment with Bydureon– Consistent with the potentially

immunogenic properties of protein and peptide pharmaceuticals1

– In clinical studies of Bydureon, approximately 45% of patients had low-titre antibodies at the study endpoint1

– Antibody titres usually diminish over time• Four clinical trials showing clinically relevant

HbA1c reduction regardless of antibody status2

• A small proportion of patients (2.6%) had higher titres and showed no glycaemic improvement1

1. Bydureon. Summary of product characteristics; 2. Fineman MS, et al. Diabetes Obes Metab 2012;14:546–54.

–2.0

–0.5

0.0

Ch

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Hb

A1c

(%

)

–1.5

–1.0

–1.6%(–15.5

mmol/mol)

–1.3%(–14.2

mmol/mol)

Antibody-negative patients

Antibody-positive patients

Reduction in mean HbA1c by antibody status2

–20

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Bydureon dosing, administration and initiation

Bydureon dosing

• Bydureon comes in a convenient single-dose kit that contains everything patients need to prepare and deliver their once-weekly injection– Injection can be administered at any

time of the day, independently of meals

– Fixed dose with no titration required– Patients can change their day of

weekly dosing as long as doses are 1 day apart*

*If a dose is missed, it should be administered as soon as practical. Thereafter, patients can resume their once-weekly dosing schedule. The use of Bydureon dose not require additional self-monitoring of blood glucose.Bydureon. Summary of product characteristics.

CONNECT

Connect the parts securely before mixing

SHAKE

Shake vigorously to mix the

medicine with the liquid

INJECT

Attach the needle, line up

the plunger with the dose line,

and inject

Flexible dosing with Bydureon

• Placeholder for video 1Dvii. Professor Kamlesh Khunti: Flexible dosing with Bydureon

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Expert sound bite

Bydureon device: Overview of the Connect, Shake, Inject process

• Contains an overview of the injection device– Straightforward dosing: Connect, Shake, Inject

Remember: Patients should follow all of the steps in the instructions for the user that comes with the single-dose kit.HCP, healthcare professional.

Tips for injecting Bydureon

• Placeholder for video 1Dviii. Gwen Hall: Tips for injecting Bydureon

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Expert sound bite

The Bydureon usability study

• A usability study of 102 individuals with Type 2 diabetes found that 88% of patients were able to prepare and deliver a dummy dose of Bydureon

Adapted from Lorenzi G, et al. Clin Diabetes 2010;28:157–62.

Subjects who succeeded in preparing and delivering a dose of Bydureon

72.6%(n=74)

Without assistance

With use of customer support helpline

15.7%(n=16)

11.8%(n=12)

Did not complete

Questionnaire responses to ‘If I only had the instructions for use, I could use the

single-dose kit at home’

69%(n=70)

22%(n=22)

7%(n=7)

2%(n=2) Strongly

agree

Agree

Neutral

Disagree/strongly disagree

Patients suitable for Bydureon

• Placeholder for video 1Dix. Professor Kamlesh Khunti: Patients suitable for Bydureon

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Expert sound bite

*Bydureon is not indicated for the management of obesity and weight change was a secondary endpoint in clinical trials.FPG, fasting plasma glucose; HCP, healthcare professional; PPG, postprandial glucose.1. Bydureon. Summary of product characteristics; 2. Buse JB, et al. Diabetes Care 2010;33:1255–61.

Expectation setting: Benefits

• To maximise adherence, a care plan should be agreed with the individual patient, including setting of expectations by the HCP, upon initiation of treatment

• Explain to patients that, due to its unique once-weekly formulation, they need to give Bydureon time to work

When you may see an effect Changes patients may notice

After four doses1,2 • FPG improvements• PPG improvements

After six or seven doses1,2 • HbA1c reductions

Over time1,2 • Feeling less hungry and eating less• Some weight loss*

Bydureon benefits; patient expectations and education

• Placeholder for video 1Dx. Gwen Hall: Bydureon benefits; patient expectations and education

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Expert sound bite

*Bydureon is not indicated for the management of obesity and weight change was a secondary endpoint in clinical trials.HCP, healthcare professional.1. Bydureon. Summary of product characteristics.

Expectation setting: Side effects

• Explain possible adverse events to your patients to help minimise discontinuation due to side effects that they may not expect– Injection bumps are normal, not harmful, and may last for 4–8 week1

– Nausea lessens over time;1 patients should speak to their HCP for help in managing symptoms if necessary

– More information is available from the local patient support programme

Explaining Bydureon to patients and setting expectations

• Placeholder for video 1Dxi. Gwen Hall: Explaining Bydureon to patients and setting expectations

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Patient treatment adherence and education

• Placeholder for video 1Dxii. Professor Kamlesh Khunti: Patient treatment adherence and education

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Expert sound bite

• Placeholder for local markets to insert information on patient support programme

Once-weekly Bydureon: Continuous glycaemic control for your patients

• Bydureon provides strong efficacy with HbA1c reductions, sustained for up to 5 years1

• Potential for sustained weight loss over 5 years* and low risk of hypoglycaemia1

• Withdrawal rate of <1% due to nausea and vomiting2

• The most frequent adverse reactions (≥5% of Bydureon patients) were mainly gastrointestinal related (nausea, vomiting, diarrhoea and constipation)2

– In addition, injection-site reactions (pruritus, nodules, erythema) were observed

• Straightforward administration that patients can manage in a once-weekly injection2,3

*Bydureon is not indicated for obesity and weight change was a secondary endpoint in clinical trials. 2

1. MacConell L, et al. Poster presented at EASD 2013. P-980; 2. Bydureon. Summary of product characteristics; 3. Lorenzi G, et al. Clin Diabetes 2010;28:157–62.

Bydureon patient successes

• Placeholder for video 1Dxiii. Gwen Hall: Bydureon patient successes

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