Bydureon® (exenatide once weekly)
clinical data slide deck
Date of approval: March 2015 | Date of expiry: March 2016
Approval code: 675,057.01
Developed with the guidance and approval of an
independent international editorial committee
Prescribing information can be found at the end of this slide deck.
Content guide
• This deck comprises 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
• 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
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 notes to provide
further information on:
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 of study design (primary analysis and extension periods)
• Detailed data from long-term extension studies
4. Cardiovascular data from Bydureon studies
5. Bydureon safety and tolerability profiles
6. Dosing, administration and tips for initiating patients on Bydureon
Introduction to Bydureon
(exenatide once-weekly)
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
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, 2014.
Slide is animated
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
Subcutaneous injection
of microsphere
suspension of
exenatide1
Individual microspheres
aggregate and initial
release of exenatide1
Microsphere degradation
and continued release of
exenatide1
Further degradation and
metabolism of microsphere
polymer provide sustained
level of exenatide1
CO2, carbon dioxide.
1. DeYoung MB, et al. Diabetes Technol Ther 2011;13:1145–54; 2. Risperdal Consta. Summary of product characteristics, 2013;
3. Vivitrol. Prescribing information. Alkermes, Inc, 2013.
Slide is animated
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
Steady state is maintained
with subsequent weekly doses
Plasma exenatide (pg/mL)
450
Weekly Bydureon
injection
400
350
Steady state achieved for
continuous glycaemic control
300
250
200
150
100
50
0
0
1
2
3
4
5
6
7
8
Time (weeks)
9
10
Figure adapted from Kim D, et al. 2007, showing mean ± standard deviation.2
1. Bydureon. Summary of product characteristics, 2014; 2. Kim D, et al. Diabetes Care 2007;30:1487–93.
11
12
13
14
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 baseline1–6
• Secondary endpoints included: Change in bodyweight, blood pressure
and CV risk markers from baseline; safety and tolerability1–6
Bydureon 2 mg
Patients with:
Type 2 diabetes
HbA1c 7.1–11.0%
(54.1–96.7 mmol/mol)
Active comparator agent(s)
Optional
Bydureon
extension
24–30 weeks
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.
Slide is animated
Overview of DURATION trials
Trial
Comparator
Background
Subjects
In EU label
DURATION-11
Exenatide BID
Open 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 glargine
Open 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 BID
Open label
Drug naïve, MET,
SU, TZD, or a
combination of these
agents
252

DURATION-66
Liraglutide (1.8 mg)
Open label
MET, SU, TZD, or a
combination of these
agents
911

• Data from DURATION-1, -2 and -3 are shown here as the primary studies included in the
Bydureon summary of product characteristics7
– When Bydureon is added to SU therapy, a reduction in the dose of SU should be considered to
reduce the risk of hypoglycaemia7
Bydureon is not indicated in Europe as monotherapy in patients uncontrolled on diet and exercise alone.7
BID, twice daily; MET, metformin; PIO, pioglitazone; QD, once 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, 2014.
DURATION-1
DURATION-1: Study details
DURATION-1: Primary analysis
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 to Bydureon
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 journal article
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: Study details (continued)
DURATION-1: 52-week extension study
Study details
N=258 (entering open-ended assessment period)
Extension study after completing a 30-week randomised, activecontrolled, open-label, non-inferiority study
Study length
22 weeks after completion of the 30-week primary study
Background therapy
None (as initial therapy) or treatment with metformin, a SU, a TZD or any
combination of these agents
Comparator to Bydureon
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
Publication type
Peer-reviewed journal article
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.
DURATION-1: Study details (continued)
DURATION-1: 3-year extension study
Study details
N=258 (entering open-ended assessment period)
Extension study after completing a 30-week randomised, activecontrolled, open-label, non-inferiority study
Study length
3-year extension (switch study)
Background therapy
None (as initial therapy) or treatment with metformin, a SU, a TZD or any
combination of these agents
Comparator to Bydureon
No comparator; pooled population included patients initated on Bydureon
and those initiated on exenatide BID and switching to Bydureon at Week
30
Study endpoints
Change in HbA1c, FPG, weight, lipid profile and SBP
Publication type
Peer-reviewed publication
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: Study details (continued)
DURATION-1: 6-year extension study
Study details
N=258 (entering open-ended assessment period; completer population
n=127)
Extension study after completing a 30-week randomised, activecontrolled, open-label, non-inferiority study
Study length
6-year extension (switch study)
Background therapy
None (as initial therapy) or treatment with metformin, a SU, a TZD or any
combination of these agents
Comparator to Bydureon
No comparator; pooled population included patients initiated on
Bydureon and those initiated on exenatide BID and switching to
Bydureon at Week 30
Study endpoints
Change in HbA1c, FPG, weight, lipid profile and SBP
Publication type
Congress abstract and poster presentation
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.
Henry RH, et al. Poster presented at ADA 2014. 964-P.
DURATION-1: Reduced HbA1c with Bydureon versus exenatide
BID over 1 year1
• At the primary endpoint of 30 weeks, HbA1c reductions from baseline were –1.9% (–20.8
mmol/mol) with Bydureon and –1.5% (–16.4 mmol/mol) with exenatide BID (p=0.0023)2
• At 1 year, patients receiving Bydureon maintained 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
0
Exenatide BID 
Bydureon
BL=8.2% (66.1 mmol/mol)
–0.5
–5
–1.0
–10
Change from BL:
–2.0%
–1.5
–15
(21.9 mmol/mol)
*
–2.0
–20
*
*
–2.5
0
6
10
14
18
*
*
* *
22
26
30
Time (weeks)
33
–2.0%
*
36
(21.9 mmol/mol)
40
Figure adapted from Buse JB, et al. 2010, showing least-squares mean ± standard error.1 *p<0.05 versus exenatide BID.
BID, twice daily; BL, baseline.
1. Buse JB, et al. Diabetes Care 2010;33:1255–61; 2. Drucker DJ, et al. Lancet 2008;372:1240–50.
44
48
52
–25
Change in HbA1c (mmol/mol)
0.0
Change in HbA1c (%)
All subjects received Bydureon
Bydureon
BL=8.3% (67.2 mmol/mol)
DURATION-1: Reduced HbA1c with Bydureon sustained
over 6 years
• HbA1c reductions were sustained over 6 years with Bydureon (mean change in HbA1c from
baseline –1.6% [95% CI, –1.9 to –1.4] [–17.5 mmol/mol])3
• 45% of all patients achieved HbA1c <7% with Bydureon, irrespective of treatment at initiation
Change in HbA1c (%)
–0.5
3 years2
(n=194)
6 years3
(n=127)
BL=8.3%
(67.2
mmol/mol)
BL=8.2%
(66.1
mmol/mol)
BL=8.2%
(66.1
mmol/mol)
–5
–10
–1.0
–1.5
0
–1.6%
–1.9%
–1.6%
–1.6%
(–17.5
mmol/mol)
(–17.5
mmol/mol)
(–20.8
(17.5
mmol/mol)
mmol/mol)
–20
– 2.0
Randomised to Bydureon
(evaluable population)
–15
Pooled population
(all Bydureon completers)
Figure adapted from Drucker DJ, et al. 2008,1 MacConell L, et al. 2013,2 and Henry RH, et al. 2014.3
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. Henry RH, et al.
Poster presented at ADA 2014. 964-P.
Change in HbA1c (mmol/mol)
0.0
30 weeks1
(n=148)
DURATION-1: Weight reductions with Bydureon versus exenatide
BID over 1 year*
• Powerful HbA1c reductions with Bydureon were accompanied by weight reductions of 4.1–4.5 kg at
1 year1
All subjects
received Bydureon
Change in bodyweight
(kg)
0
Bydureon
BL=103 kg
–1
Exenatide BID  Bydureon
BL=102 kg
–2
–3
Change from BL:
–4.1 kg
–4
–4.5 kg
–5
0
6
10
14
18
22
26
30
36
40
Time (weeks)
Figure adapted from Buse JB, et al. 2010, showing least squares mean ± standard error.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.
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, 2014.
44
48
52
DURATION-1: Weight reductions with Bydureon sustained
over 6 years*
• Weight reductions with Bydureon were sustained over 6 years (mean reductions from baseline
–4.3 kg [95% CI, –6.0 to –2.6])
30 weeks1
(n=148)
3 years2
(n=194)
6 years3
(n=127)
BL=102 kg
BL=101 kg
BL=101 kg
Change in bodyweight (kg)
0
–1
–2
–3
–2.3 kg
–1.6%
(17.5
mmol/mol)
–4
–5
–4.0 kg
–4.3 kg
Randomised to Bydureon
(evaluable population)
Pooled population
(all Bydureon completers)
Figures adapted from Drucker DJ, et al. 2008,1 MacConell L, et al. 2013,2 and Henry RH, et al. 2014.3
*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.
1. Drucker DJ, et al. Lancet 2008;372:1240–50; 2. MacConell L, et al. Diabetes Metab Syndr Obes 2013;6:31–41; 3. Henry RH, et al.
Poster presented at ADA 2014. 964-P; 4. Bydureon. Summary of product characteristics, 2014.
DURATION-2
DURATION-2: Study details
DURATION-2: Primary analysis
Study details
N=491 (ITT population)
Randomised, double-blind, double-dummy, active-controlled superiority
trial
Study length
26 weeks
Background therapy
Metformin
Comparators to
Bydureon
Sitagliptin 100 mg QD
Pioglitazone 45 mg QD
Primary endpoint
Change in HbA1c from baseline at Week 26
Secondary endpoints
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; patientreported HRQoL; safety and tolerability
Publication type
Peer-reviewed journal article
CV, cardiovascular; FPG, fasting plasma glucose; HRQoL, health-related quality of life; ITT, intent-to-treat; SMBG, self-monitored blood glucose;
QD, once daily.
Bergenstal RM, et al. Lancet 2010;376:431–9.
DURATION-2: Study details (continued)
DURATION-2: 52-week extension study
Study details
N=364 (entering extension study)
Extension study after completing a 26-week randomised, double-blind,
double-dummy, superiority trial
Study length
26 weeks with a 26-week extension (switch study)
Background therapy
Metformin
Comparators to
Bydureon
Patients initiated on sitagliptin 100 mg QD  Bydureon at Week 26
Patients initiated on pioglitazone 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
Publication type
Peer-reviewed journal article
CV, cardiovascular; FPG, fasting plasma glucose; QD, once daily.
Wysham C, et al. Diabet Med 2011;28:705–14.
DURATION-2: Reduced HbA1c with Bydureon versus sitagliptin and
pioglitazone
• At the primary endpoint of 26 weeks, HbA1c changes from baseline were –1.5% (–16.4 mmol/mol)
with Bydureon, –0.9% (–9.8 mmol/mol) with sitagliptin and –1.2% (–13.1 mmol/mol) with
pioglitazone (p<0.05 for Bydureon vs both comparators)1
• Significant HbA1c reductions with Bydureon were achieved at 1 year, regardless of initial therapy2
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
Change from Week 26 to Week 52:
–0.31% (95 % CI, –0.50 to –0.13)* (–3.4 mmol/mol)
0.06% (95 % CI, –0.13 to 0.25) (0.7 mmol/mol)
–0.10% (95 % CI, –0.29 to 0.09) (–1.1 mmol/mol)
–0.5
–5
–10
–1.0
–15
–1.5
–20
–2.0
0
4 6
10
14
18
22
26
30
34
40
46
52
Time (weeks)
Graph adapted from Wysham C, et al. 2011, showing data for the evaluable population as least squares mean ± standard error.2 *p<0.05 versus Week 26.
BL, baseline; CI, confidence interval.
1. Bergenstal RM, et al. Lancet 2010;376:431–9; 2. Wysham C, et al. Diabet Med 2011;28:705–14.
Change in HbA1c from
baseline (mmol/mol)
Change in HbA1c (%)
0.0
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 reductions2
Blinded period
Open-label period
Change in bodyweight (kg)
5
Bydureon, BL=90 kg
Sitagliptin  Bydureon, BL=86 kg
Pioglitazone  Bydureon, BL=86 kg
4
3
2
1
Change from Week 26:
0
–3.0 kg (95 % CI, –3.7 to –2.3)†
–1
0.7 kg (95 % CI, 0.1 to 1.4)†
–2
–1.1 kg (95% CI, –1.8 to –0.5)†
–3
0
4 6
10
14
18
22
26
30
34
40
46
52
Time (weeks)
Graph adapted from Wysham C, et al. 2011, showing data for the evaluable population (least squares mean ± standard error).2 †p<0.05 versus Week 26.
*Bydureon is not indicated for the treatment of obesity and weight change was a secondary endpoint in clinical trials. 3
BL, baseline; CI, confidence interval.
1. Bergenstal RM, et al. Lancet 2010;376:431–9; 2. Wysham C, et al. Diabet Med 2011;28:705–14; 3. Bydureon. Summary of product characteristics, 2014.
DURATION-3
DURATION-3: Study details
DURATION-3: Primary analysis
Study details
N=456 (ITT population)
Open-label, randomised, parallel-group study
Study length
26 weeks
Background therapy
Metformin ± SU
Comparator to
Bydureon
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; HRQoL; 1,5anhydroglucitol; safety and tolerability
Publication type
Peer-reviewed journal article
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; HRQoL, health-related quality of life; SMBG, self-monitored blood glucose; SU, sulphonylurea.
Diamant M, et al. Lancet 2010;375:2234–43.
DURATION-3: Study details (continued)
DURATION-3: Planned interim analysis at 84 weeks of open-ended
extension study
Study details
N=390 (entering extension study)
Open-label, randomised, parallel-group study
Study length
26 weeks with open-ended extension study; interim analysis at 84 weeks
Background therapy
Metformin ± SU
Comparator to Bydureon
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
Publication type
Peer-reviewed journal article
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: Study details (continued)
DURATION-3: 3-year extension study
Study details
N=390 (entering extension study; completer population n=287)
Open-label, randomised, parallel study
Study length
26 weeks with 3-year extension
Background therapy
Metformin ± SU
Comparator to Bydureon
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 measures
Patients achieving HbA1c <7.0% (<53.0 mmol/mol) and ≤6.5%
(≤47.5 mmol/mol); bodyweight; FPG; SMBG, fasting serum lipids;
patient-reported outcomes; safety and tolerability
Exploratory measures
Blood CRP concentrations; urinary ACR; WHR
Publication type
Peer-reviewed publication
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; CRP, C-reactive protein; FPG, fasting plasma glucose; SMBG, self-monitored blood glucose; SU, sulphonylurea;
WHR, waist-to-hip ratio.
Diamant M, et al. Lancet Diabetes Endocrinol 2014;2:464–73.
DURATION-3: Reduced HbA1c with Bydureon versus basal insulin
over 3 years
• At the primary endpoint of 26 weeks, HbA1c reductions from baseline were –1.5% (–16.4 mmol/mol)
with Bydureon and –1.3% (–14.2 mmol/mol) with insulin glargine (p=0.017)1
• Bydureon-treated patients experienced significantly greater HbA1c reductions at 3 years than those
treated with insulin glargine2
Change from BL:
9
70
–0.81 ± 0.07% (–8.9 mmol/mol)
8
60
HbA1c (%)
–1.01 ± 0.7% (–11.0 mmol/mol)*
6
50
5
40
4
30
3
20
2
1
Bydureon, BL=8.3% (67.2 mmol/mol; n=228)
Insulin glargine, BL=8.3% (67.2 mmol/mol; n=220)
10
0
0
0
8
18 26
36
48
60
96
72
84
Time (weeks)
108
120
132
144
156
Graph adapted from Diamant M, et al. 2014, showing data for the modified intent-to-treat population as least squares mean ± standard error.2 *p=0.03.
BL, baseline.
1. . Diamant M, et al. Lancet 2010;375:2234–43; 2. Diamant M, et al. Lancet Diabetes Endocrinol 2014;2:464–73.
HbA1c (mmol/mol)
7
DURATION-3: Weight change with Bydureon versus basal insulin
over 3 years
• Treatment with Bydureon resulted in significant weight reduction instead of weight gain with insulin
glargine over 3 years1
Bydureon, BL=91.2 kg (n=233)
Insulin glargine, BL=90.6 kg (n=222)
Change in bodyweight (kg)
4
Change from BL:
+2.01 ± 0.28 kg
2
0
–2
–2.49 ± 0.28 kg*
–4
0
8
18 26
36
48
60
72
84 96
Time (weeks)
108 120 132 144 156
Graph adapted from Diamant M, et al. 2014, showing data for the modified intent-to-treat population as least squares mean ± standard error.1 *p<0.001.
BL, baseline.
Bydureon is not indicated for the treatment of obesity and weight change was a secondary endpoint in clinical trials. 2
1. Diamant M, et al. Lancet Diabetes Endocrinol 2014;2:464–73; 2. Bydureon. Summary of product characteristics, 2014.
DURATION-3: Individual associations between HbA1c and body
weight with Bydureon versus insulin glargine at 26 weeks*1
Weight change from baseline (kg)
16
12
16%
0%
63%
5%
8
Bydureon
Insulin glargine
4
0
–4
–8
–12
79%
4%
31%
1%
–16
–6
–4
–2
0
2
HbA1c (%) change from baseline
Modified ITT population, N=448.
*Figure adapted from Diamant M, et al. Lancet 2010.1
*Bydureon is not indicated for the management of obesity and weight change was a secondary endpoint in clinical trials. 2
1. Diamant M, et al. Lancet 2010;375:2234–43; Bydureon. Summary of product characteristics, 2014.
4
6
DURATION-3: Incidence of minor hypoglycaemia versus insulin
glargine
• Bydureon was associated with a lower rate of minor hypoglycaemia than insulin glargine at 84
Patients reporting minor
hypoglycaemia (%)
weeks1
100
90
80
70
60
50
40
30
20
10
0
Bydureon (n= 233)
Insulin glargine (n=223)
54%
32%
*
8%
n=13
n=51
Metformin background
*
24%
n=36
n=17
Metformin + SU
background
Graph adapted from Diamant et al. Diabetes Care 2012.1 *p<0.001. Minor hypoglycaemia was defined any time a paitent felt that he or she had a sign or symptom
of hypoglycaemia that was associated with concurrent blood glucose <3.0 mmol/L and that was either self-treated by the patient or resolved independently.1 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, during the first 26 weeks. 1
• The exposure-adjusted rate of overall hypoglycaemia at 3 years was three times higher with insulin
glargine (0.9 events/patient/year) than with Bydureon (0.3 events/patient/year)2
– 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 hypoglycaemia 3
SU, sulphonylurea.
1. Diamant M, et al. Diabetes Care 2012;35:683–9; 2. Diamant M, et al. Lancet Diabetes Endocrinol 2014;2:464–73; 3. Bydureon. Summary of product
characteristics, 2014.
Change in CV risk markers with Bydureon
Evidence from DURATION-1
Bydureon is not indicated for the management of blood pressure or cholesterol.1
CV, cardiovascular.
1. Bydureon. Summary of product characteristics, 2014.
DURATION-1: Changes in blood pressure over 1 year with
Bydureon
• Over 1 year in the DURATION-1 study, improvements from baseline in blood pressure were seen
with Bydureon treatment1,2
SBP
Baseline
Week 301
n=148
128
Year 12
n=148
129
DBP
Week 301
n=148
78
Year 12
n=148
78
Change in BP (mmHg)
0
–1.7
mmHg
–1
–2.8
mmHg
–2
–3
–4
–4.7
mmHg
–5
–6
–6.2
mmHg
–7
Figure adapted from Drucker DJ, et al. 20081 and Buse JB, et al. 2010,2 showing ITT population of patients randomised to Bydureon (n=148).
• At 1 year, 50% of patients with a high baseline SBP (≥130 mmHg) achieved
a normal SBP2
Bydureon is not indicated for the management of blood pressure or cholesterol.3
DBP, diastolic blood pressure; SBP, systolic blood pressure.
1. Drucker DJ, et al. Lancet 2008;372:1240–50; 2. Buse JB, et al. Diabetes Care 2010;33:1255–61;
3. Bydureon. Summary of product characteristics, 2014.
DURATION-1: Changes in lipid profile at 1 year with Bydureon
• Over 1 year in the DURATION-1 study, improvements from baseline in plasma lipids were
observed with Bydureon treatment1,2
Total cholesterol
BL=4.49
–0.1
–0.2
–0.3
–0.31
mmol/L
BL=4.40
–0.25
mmol/L
–0.4
HDL-C
Week 301
Year 12
BL=2.37
–0.13
mmol/L
BL=2.30
Week 301
Year 12
BL=1.88
BL=1.82
0.1
0.0
–0.1
–0.09
mmol/L
–0.2
–0.3
Triglycerides
0.1
Change from
BL (mmol/L)
Change from
BL (mmol/L)
0.0
Year
12
0.0
–0.1
Week
301
Year
12
+0.02
mmol/L
BL=1.14
BL=1.14
–0.02
mmol/L
Change from
BL (%)
Change from
BL (mmol/L)
Week
LDL-C
301
0
–5
–15%
–10
–15
–15%
Figures adapted from Drucker DJ, et al. 20081 and Buse JB, et al. 2010,2 showing ITT population of patients randomised to Bydureon (n=148).
• Improvements were maintained for up to 6 years3
Bydureon is not indicated for the management of blood pressure or cholesterol.4
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. Buse JB, et al. Diabetes Care 2010;33:1255–61; 3. Henry RH, et al. Poster presented at
ADA 2014. 964-P; 4. Bydureon. Summary of product characteristics, 2014.
Bydureon safety and tolerability profile
Bydureon: Summary of safety and tolerability profile
• As with other GLP-1 receptor agonists,1–4 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 occurred1
• Most adverse reactions associated with Bydureon were mild to moderate in intensity1
• There have been rare, spontaneously reported events of acute pancreatitis and renal
failure. If pancreatitis is suspected, Bydureon should be discontinued1
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.
1. Bydureon. Summary of product characteristics, 2014; 2. Byetta. Summary of product characteristics, 2014; Victoza. Summary of product
characteristics, 2014; 4. Lyxumia. Summary of product characteristics, 2014.
Very common and common adverse reactions reported with
Bydureon in clinical trials
• Most adverse reactions associated with BYDUREON were mild to moderate in intensity and only infrequently* led
to discontinuation
System organ class/adverse reaction
terms
Metabolism and nutrition disorders
Frequency of occurrence†
Very common (≥1/10)
Hypoglycaemia (with a SU)‡
Nausea‡
Vomiting‡
Diarrhoea‡
Constipation
Dyspepsia‡
Abdominal pain‡
Gastroesophageal reflux disease‡
Abdominal distension‡
Eructation
Flatulence‡
Hyperhidrosis‡
Skin and subcutaneous tissue disorders
General disorders and administration site
conditions
Decreased appetite‡
Headache‡
Dizziness‡
Nervous system disorders
Gastrointestinal disorders
Common (≥1/100 to <1/10)
Injection-site pruritus
Fatigue‡
Injection-site erythema
Injection-site rash
Somnolence
*The incidence of withdrawal due to adverse events in Bydureon-treated patients during the 30-week controlled trial was 6%. †Rate based on Bydureon clinical trial data (N=592
total; n=135 patients on SU) When Bydureon is added to SU therapy, a reduction in the dose of SU should be considered to reduce the risk of hypoglycaemia. ‡Reactions were
in the same frequency grouping in the exenatide BID group. 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.
• There have been rare, spontaneously reported events of acute pancreatitis and renal failure.
If pancreatitis is suspected, Bydureon should be discontinued
BID, twice daily; SU, sulphonylurea; TZD, thiazolidinedione.
Bydureon. Summary of product characteristics, 2014.
Very common and common adverse reactions observed from
clinical trial experience that were not observed with Bydureon at an
incidence of ≥1%
System organ class/adverse reaction
terms
Frequency of occurrence*
Very common (≥1/10)
Common (≥1/100 to <1/10)
Skin and subcutaneous tissue disorders
Hyperhidrosis
General disorders and administration site
conditions
Asthenia
Feeling jittery
*Rate based on Bydureon clinical trial data (N=592 total; n=135 patients on SU).
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 (26week 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, 2014.
Handling nausea that may occur with Bydureon treatment
Incidence of nausea
(%)
• 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
100
80
60
40
20
0
Weeks
Figure adapted from Maggs D, et al. 2012.5
• In a 52-week trial, even when patients experienced nausea, it did not affect their
reported level of treatment satisfaction with Bydureon6
GLP-1, glucagon-like peptide-1.
1. Bydureon. Summary of product characteristics, 2014; 2. Byetta. Summary of product characteristics 2014 3. Victoza. Summary of product
characteristics, 2014; 4. Lyxumia. Summary of product characteristics, 2014; 5. Maggs D, et al. Presented at EASD 2012. Presentation #4;
6. Best JH, et al. Diabet Med 2009;26:722–8.
Handling injection-site reactions that may occur with Bydureon
treatment
Injection-site reactions versus bumps
Injection-site bumps
• Injection-site reactions associated
• Small, raised nodules that very
•
•
•
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
frequently occur at the injection site
– These are consistent with known
properties of poly (D,L-lactide coglycolide) polymer microsphere
technology
Size of bump
• Bumps are normally harmless and
resolve over 4–8 weeks
Bydureon. Summary of product characteristics, 2014.
Contraindications and special warnings and precautions
Contraindications
Hypersensitivity to the active substance or to any of the excipients.
Warnings and precautions
Not 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 increase 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 required for patients with mild renal impairment (CrCl 50–80 mL/min). Very limited experience
in moderate renal impairment (CrCl 30–50 mL/min). Not recommended in patients with moderate renal impairment,
severe renal impairment (CrCl <30 mL/min) or end-stage renal disease.
• Severe gastrointestinal disease
Not recommended.
Please see the Bydureon summary of product characteristics for full safety information.
CrCl, creatinine clearance.
Bydureon. Summary of product characteristics, 2014.
Contraindications and special warnings and precautions (continued)
• Acute pancreatitis
Rare, 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 suspected, discontinue use of Bydureon and other potentially suspect medicinal products. Do not
resume Bydureon after pancreatitis has been diagnosed.
• Concomitant medicinal products
Concurrent use of Bydureon with insulin, meglitinides, alpha-glucosidase inhibitors, dipeptidyl peptidase-4 inhibitors
or other GLP-1 receptor agonists has not been studied. The concurrent use of Bydureon and exenatide BID has
not been studied and is not recommended.
• Weight loss
Rapid weight loss at a rate of >1.5 kg per week has been reported with exenatide, which may have harmful
consequences.
• Discontinuation of treatment
The 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.
Please see the Bydureon summary of product characteristics for full safety information.
BID, twice daily; GLP-1, glucagon-like peptide-1.
Bydureon. Summary of product characteristics, 2014.
Drug interactions
No dose adjustment required for medicinal products sensitive to delayed gastric emptying.
• Warfarin and cumarol derivatives
Increased INR reported during concomitant use of warfarin and exenatide. INR should be monitored during
initiation of Bydureon.
• HMG CoA reductase inhibitors
Concomitant use with exenatide was not associated with consistent changes in lipid profiles. Lipid profiles should
be monitored as appropriate.
Please see the Bydureon summary of product characteristics for full safety information.
AUC, area under curve; BID, twice daily; HMG, hydroxy methyl glutaryl coenzyme A; INR, international normalised ratio.
Bydureon. Summary of product characteristics, 2014.
Anti-exenatide antibodies
• Patients may develop antibodies to
Reduction in mean HbA1c by antibody status2
exenatide following treatment with
Bydureon
•
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
Change in HbA1c (%)
•
0.0
Antibodynegative
patients
Antibodypositive
patients
n=280
n=371
–5
–0.5
–1.3%
–1.0
–1.6%
–1.5
0
(–15.5
mmol/mol)
–2.0
1. Bydureon. Summary of product characteristics, 2014; 2. Fineman MS, et al. Diabetes Obes Metab 2012;14:546–54.
–10
(–14.2
mmol/mol)
–15
–20
Change in HbA1c (mmol/mol)
– 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
time1
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*
CONNECT
SHAKE
INJECT
Connect the
parts securely
before mixing
Shake
vigorously
to mix the
medicine with
the liquid
Attach the
needle, line up
the plunger with
the dose line,
and inject
*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 does not require additional self-monitoring of blood glucose.
Bydureon. Summary of product characteristics, 2014.
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
Bydureon. Summary of product characteristics, 2014.
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
Subjects who succeeded in preparing
and delivering a dose of Bydureon
Questionnaire responses to ‘If I only
had the instructions for use, I could
use the single-dose kit at home’
2%
Did not
complete
(n=2)
7%
11.8%
(n=7)
(n=12)
With use of
customer
15.7%
support
(n=16)
helpline
Strongly
agree
Agree
Neutral
Disagree/
strongly
disagree
22%
(n=22)
72.6%
(n=74)
(n=70)
Without
assistance
Adapted from Lorenzi G, et al. Clin Diabetes 2010;28:157–62.
69%
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 doses1,3
• HbA1c reductions
Over time1
• Feeling less hungry and eating less
• Most patients will experience weight
reduction*
*Bydureon is not indicated for the management of obesity and weight change was a secondary endpoint in clinical trials. 1
FPG, fasting plasma glucose; HCP, healthcare professional; PPG, postprandial glucose.
1. Bydureon. Summary of product characteristics, 2014; 2. Blevins T, et al. J Clin Endocrinol Metab 2011;96:1301–10; 3. Drucker DJ, et al. Lancet 2008;
372:1240–50.
Once-weekly Bydureon: Continuous glycaemic control for your
patients
• Bydureon provides powerful efficacy with HbA1c reductions, sustained for up
to 6 years1
• Potential for sustained weight reduction over 6 years* and low risk of
hypoglycaemia†1,2
• 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
†SUs are associated with an increased 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 hypoglycaemia.2
1. Henry RH, et al. Poster presented at ADA 2014. 964-P; 2. Bydureon. Summary of product characteristics, 2014; 3. Lorenzi G, et al.
Clin Diabetes 2010;28:157–62.
This information is consistent with the UK marketing authorisation. Please refer to your
local prescribing information for full details.
This information is consistent with the UK marketing authorisation. Please refer to your
local prescribing information for full details.