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Bydureon® Educate By Expert toolkit

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Presentation on theme: "Bydureon® Educate By Expert toolkit"— Presentation transcript:

1 Bydureon® Educate By Expert toolkit
Scientific slides: Bydureon clinical data Thank you for choosing to use these slides from the Bydureon® Educate By Expert toolkit to discuss the Bydureon clinical data. To ensure the high quality and relevance of the content, this toolkit has been developed with the guidance and approval of an independent international editorial committee: Associate Professor Dr Javier Ampudia Blasco (Specialist in Endocrinology and Nutrition, Spain) Paul Dromgoole (Diabetes Specialist Nurse and Clinical Lecturer, UK) Gwen Hall (Diabetes Specialist Nurse, UK) Professor Stephan Jacob (Specialist in Endocrinology and Diabetes, Germany) Professor Kamlesh Khunti (Primary Care Diabetes and Vascular Medicine, UK) Dr Orville Kolterman (Senior Vice President and Chief Medical Officer, Amylin Pharmaceuticals, US) Date of preparation: Apri l ENDORSED Developed with the guidance and approval of an independent international editorial committee

2 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 i Expert sound bite DCCT, Diabetes Control and Complications Trial; IFFC, International Federation of Clinical Chemistry and Laboratory Medicine.

3 Executive summary This slide deck covers the following topics and contains speaker notes to assist presentation: Introduction to Bydureon, microsphere technology and the steady-state principle Overview of the Bydureon clinical trial programme (DURATION studies) Data from the Bydureon DURATION-1, -2 and -3 studies Overview Detailed data from long-term extension studies Cardiovascular data from Bydureon studies Bydureon safety and tolerability Dosing, administration and tips for initiating patients on Bydureon

4 Introduction to Bydureon

5 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 Main talking point: Bydureon is the first and only once-weekly treatment for Type 2 diabetes, approved in the EU in It is a GLP-1 receptor agonist indicated as add-on to one or more oral antidiabetic drugs.1 GLP-1, glucagon-like peptide-1. Reference Bydureon. Summary of product characteristics. 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.

6 Formulating exenatide into a long-release formulation
Expert sound bite Placeholder for video 1Di. Dr Orville Kolterman: Formulating exenatide into a long-release formulation

7 Bydureon’s patented microsphere technology enables once-weekly dosing
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 Main talking point: Bydureon’s patented microsphere delivery system provides continuous therapeutic levels of exenatide that enables once-weekly dosing. Notes: Patented Medisorb® microspheres are a biodegradable polymer that dissipates into CO2 and water1 The microspheres deliver a constant presence of exenatide with a single weekly injection1 CO2, carbon dioxide. Reference DeYoung MB, et al. Diabetes Technol Ther 2011;13:1145–54. 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.

8 Bydureon microsphere technology
Placeholder for microsphere technology video

9 The microsphere technology
Expert sound bite Placeholder for video 1Dii. Dr Orville Kolterman: The microsphere technology

10 Steady state is reached by 6–7 weeks1,2
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 Time (weeks) 450 400 350 300 250 200 150 100 50 Plasma exenatide (pg/mL) 1 2 3 4 5 6 7 8 9 10 11 12 13 14 Weekly Bydureon injection Steady state achieved for continuous glycaemic control Main talking point: The microsphere delivery system provides continuous therapeutic levels of exenatide that reach therapeutic concentrations within 2 doses and steady-state after 6 or 7 doses.1,2 Notes: [Click reveals first part of graph; second part animates automatically after a short pause] After the initial dose of Bydureon, there is an increase in plasma exenatide concentration that declines over time2 Upon the second dose, diffusion of exenatide from the microsphere continues from the initial dose2 It takes about 2 weeks to achieve Bydureon concentrations in the therapeutic range (50 pg/mL)2 Steady-state exenatide concentration, which is in the therapeutic range, is reached at 6–7 weeks2 Since therapeutic concentrations of exenatide are achieved over time, individuals should expect glucose control to gradually improve over time2 Steady-state plasma concentrations of exenatide are maintained with subsequent weekly dosing2 References Bydureon. Summary of product characteristics. Kim D, et al. Diabetes Care 2007;30:1487–93. 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.

11 Bydureon clinical trial programme
The following slides provide an overview of the core design of the DURATION clinical trials for Bydureon.

12 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 Patients with: Type 2 diabetes HbA1c 7.1–11.0% (54.1–96.7 mmol/mol) Optional Bydureon extension Bydureon 2 mg Active comparator agent(s) 24–30 weeks Main talking point: This is the core design of the DURATION clinical trials. Notes: DURATION stands for Diabetes Therapy Utilisation: Researching Changes in A1c, Weight, and Other Factors Through Intervention with Exenatide Once Weekly The purpose of the DURATION trials is to examine the effects of Bydureon on glucose control and safety in subjects with Type 2 diabetes managed with diet modification and exercise and/or oral antidiabetic drugs1–6 All of the DURATION trials were designed as either head-to-head comparator-controlled or multiple comparator-controlled studies, versus active comparators1–6 Type 2 diabetes patients with an HbA1c of 7.1–11.0% were treated with Bydureon or comparator agents for 24–30 weeks (primary endpoints)1–6 Patients were monitored to compare the effect on glucose control (change in HbA1c) to examine the safety and tolerability as well as the change in bodyweight from baseline to endpoint1–6 References Drucker DJ, et al. Lancet 2008;372:1240–50. Bergenstal RM, et al. Lancet 2010:376:431–9. Diamant M, et al. Lancet 2010:375;2234–43. Russell-Jones D, et al. Diabetes Care 2012;35:252–8. Blevins T, et al. J Clin Endocrinol Metab 2011;96:1301–10. Buse JB, et al. Lancet 2013;381:117–24. 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. 12

13 Overview of DURATION trials
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 Drug naïve, mono and combo failures 252 DURATION-66 Liraglutide (1.8 mg) Open label Mono and combo failures 911 Main talking point: Six DURATION studies were conducted in total. [Click fades bottom half of table]. Data from DURATION-1, -2 and -3 only are presented in this deck, as these are the only studies that are included in the summary of product characteristics and have also resulted in an indication for Bydureon. References Drucker DJ, et al. Lancet 2008;372:1240–50. Bergenstal RM, et al. Lancet 2010:376:431–9. Diamant M, et al. Lancet 2010:375;2234–43. Russell-Jones D, et al. Diabetes Care 2012;35:252–8. Blevins T, et al. J Clin Endocrinol Metab 2011;96:1301–10. Buse JB, et al. Lancet 2013;381:117–24. 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.

14 Overview of DURATION-1, -2 and -3
The following slides provide an overview of the HbA1c and weight data from DURATION-1, -2 and -3. Both primary endpoints and extension studies will be shown.

15 Reduced HbA1c with Bydureon at the DURATION-1, -2 and -3 trials’ primary analysis
30 weeks (N=295) DURATION-22 26 weeks (N=491) –2.0 –1.5 –1.0 –0.5 0.0 Change in HbA1c from baseline (%) DURATION-33 26 weeks (N=456) –1.5% (–16.4 mmol/mol) Exenatide BID 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) Sitagliptin 100 mg QD BL=8.5% (69.4 mmol/mol) –1.9%* (–20.8 mmol/mol) –1.2% (–13.1 mmol/mol) Pioglitazone 45 mg QD BL=8.5% (69.4 mmol/mol) –1.5%‡ –1.3% (–14.2 mmol/mol) Insulin glargine BL=8.3% (67.2 mmol/mol) –20 –15 –10 –5 Change in HbA1c from baseline (mmol/mol) Main talking point: In the DURATION-1, -2 and -3 trials, Bydureon demonstrated significant HbA1c reductions versus active comparators at the primary endpoints. Notes: The primary endpoint was achieved in DURATION-1, -2 and -3, as demonstrated by significant reduction in HbA1c for Bydureon versus maximum daily doses of exenatide BID (DURATION-1), sitagliptin and pioglitazone (DURATION-2), and insulin glargine titrated to target (DURATION-3)1–3 Data were based on the modified intent-to-treat populations1–3 Clinical trials are conducted under varying conditions, and results from individual trials cannot be directly compared BID, twice daily. References Drucker DJ, et al. Lancet 2008;372:1240–50 Bergenstal RM, et al. Lancet 2010;376:431–39. Diamant M, et al. Lancet 2010;375:2234–43. Figure adapted from Drucker DJ, et al. 2008,1 Bergenstal RM, et al. 2010,2 and Diamant M, et al N-values represent ITT population. *p= 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.

16 Reduced HbA1c with Bydureon sustained throughout the DURATION-1, -2 and -3 trials’ extension studies
5 years (N=158) DURATION-22 52 weeks (N=364) –2.0 –1.5 –1.0 –0.5 0.0 Change in HbA1c from baseline (%) DURATION-33 3 years (N=390) Bydureon –1.6% (–17.5 mmol/mol) –1.4% (–16.3 mmol/mol) Sitagliptin 100 mg QD  Bydureon –1.6% (–17.5 mmol/mol) Bydureon (pooled population) Pioglitazone 45 mg QD  Bydureon –1.0%* (–10.9 mmol/mol) –0.8% (–8.7 mmol/mol) Insulin glargine 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) –20 –15 –10 –5 Change in HbA1c from baseline (mmol/mol) Main talking point: In the DURATION-1, -2 and -3 trials, HbA1c reductions with Bydureon were maintained across the extension period. Notes: In the DURATION-1 trial, all patients receiving exenatide BID switched to Bydureon at the 30-week primary endpoint and the data shown here are from the pooled populations. Final HbA1c reduction from baseline in the completer population at Year 5 was –1.6% (–17.5 mmol/mol)1 In the DURATION-2 trial, all patients receiving sitagliptin or pioglitazone switched to Bydureon at the 30-week primary endpoint. HbA1c reductions were maintained to Week 52 in patients initially receiving Bydureon, and those initially treated with sitagliptin or pioglitazone experienced further HbA1c reductions from Weeks 30–52; overall changes from baseline were –1.4% (–15.3 mmol/mol) and –1.6% (–17.5 mmol/mol), respectively2 In the DURATION-3 trial, significant HbA1creductions versus insulin glargine were maintained at Year 33 Data for DURATION-1 are the completer population; DURATION-2 and -3 are based on the modified intent-to-treat populations1–3 Clinical trials are conducted under varying conditions, and results from individual trials cannot be directly compared BID, twice daily. References MacConell L, et al. Poster presented at EASD P-980. Wysham C, et al. Diabet Med 2011;28:705–14. Trautmann M. Presented at ADA 2013:67-OR. Figure adapted from MacConell L, et al. 2013,1 Wysham C, et al. 2011,2 and Trautmann M, 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 P-980; 2. Wysham C, et al. Diabet Med 2011;28:705–14; 3. Trautmann M. Presented at ADA 2013:67-OR.

17 Change in bodyweight from baseline (kg)
Reduced weight with Bydureon at the DURATION-1, -2 and -3 trials’ primary analysis Bydureon DURATION-11 30 weeks (N=295) DURATION-22 26 weeks (N=491) –4 –2 2 4 Change in bodyweight from baseline (kg) DURATION-33 26 weeks (N=456) Exenatide BID Sitagliptin 100 mg QD Pioglitazone 45 mg QD Insulin glargine –3.6 kg* BL=102 kg –2.3 kg†‡ BL=90 kg –0.8 kg BL=88 kg –3.7 kg +2.8 BL=86 kg –2.6 kg§ BL=91.2 kg +1.4 kg BL=90.6 kg Main talking point: This slide shows a summary of a secondary endpoint for DURATION-1, -2 and -3, the change in bodyweight from baseline to the primary endpoint. Notes: The secondary endpoint was achieved, as demonstrated by significant reduction in bodyweight for Bydureon versus maximum daily doses of sitagliptin, pioglitazone (DURATION-2) and insulin glargine titrated to target (DURATION-3)2,3 Similar weight reductions were achieved in the DURATION-1 study of Bydureon versus exenatide BID1 Data were based on the modified intent-to-treat populations1–3 Clinical trials are conducted under varying conditions, and results from individual trials cannot be directly compared Bydureon is not indicated for the treatment of obesity and weight change was a secondary endpoint in clinical trials.4 BID, twice daily. References Drucker DJ, et al. Lancet 2008;372:1240–50. Bergenstal RM, et al. Lancet 2010;376:431–39. Diamant M, et al. Lancet 2010;375:2234–43. Bydureon. Summary of product characteristics. Figure adapted from Drucker DJ, et al. 2008,1 Bergenstal RM, et al. 2010,2 and Diamant M, et al *p=0.89 versus exenatide BID; †p= versus sitagliptin; ‡p< versus pioglitazone; §p< 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.

18 Change in bodyweight from baseline (kg)
Reduced weight with Bydureon sustained throughout the DURATION-1, -2 and -3 trials’ extension studies Bydureon DURATION-11 5 years (N=158) DURATION-22 52 weeks (N=364) DURATION-33 3 years (N=390) Sitagliptin 100 mg QD  Bydureon Bydureon (pooled population) Pioglitazone 45 mg QD  Bydureon Insulin glargine –4 –2 2 Change in bodyweight from baseline (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 Main talking point: In the DURATION-1, -2 and -3 trials, patients receiving Bydureon experienced an overall reduction in bodyweight from baseline. Notes: In the DURATION-1 trial, all patients receiving exenatide BID switched to Bydureon at the 30-week primary endpoint and the data shown here are from the pooled populations. Final weight reduction from baseline in the completer population at Year 5 was –2.8 kg1 In the DURATION-2 trial, all patients receiving sitagliptin or pioglitazone switched to Bydureon at the 30-week primary endpoint. Weight reductions were maintained to Week 52 in patients initially receiving Bydureon, and those initially treated with sitagliptin or pioglitazone experienced further weight reductions from Weeks 30–52, with overall changes from baseline of –1.9 kg and –0.2 kg, respectively2 Sitagliptin  Bydureon change from Week 26 to Week 52: –1.1 kg (p=0.0006) Pioglitazone  Bydureon change from Week 26 to Week 52: –3.0 kg (p<0.0001) In the DURATION-3 trial, significant HbA1creductions versus insulin glargine were maintained at Year 33 Data were based on the modified intent-to-treat populations1–3 Clinical trials are conducted under varying conditions, and results from individual trials cannot be directly compared Bydureon is not indicated for the treatment of obesity and weight change was a secondary endpoint in clinical trials.4 BID, twice daily. References MacConell L, et al. Poster presented at EASD P-980. Wysham C, et al. Diabet Med 2011;28:705–14. Trautmann M. Presented at ADA 2013:67-OR. Bydureon. Summary of product characteristics. Figure adapted from MacConell L, et al. 2013,1 Wysham C, et al. 2011,2 and Trautmann M, *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 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.

19 Benefits of Bydureon i Expert sound bite Placeholder for video 1Diii. Professor Kamlesh Khunti: Benefits of Bydureon

20 DURATION-1 The following slides present detailed study information and results from the DURATION-1 clinical trial of Bydureon versus exenatide BID. BID, twice daily.

21 DURATION-1: Study details
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 Main talking point: The DURATION-1 clinical trial examined efficacy and safety of Bydureon versus exenatide BID at the primary endpoint of Week 30. Notes: Patients either received the study drugs as initial therapy, or were on a background of metformin, a SU, a TZD or a combination of these agents BID, twice daily; SU, sulphonylurea; TZD, thiazolidinedione. Reference Drucker DJ, et al. Lancet 2008;372:1240–50. 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.

22 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) Background therapy None (as initial therapy) or treatment with metformin, a SU, a TZD or any combination of these agents 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 Publication type Peer-reviewed publication Main talking point: The DURATION-1 clinical trial extension examined long-term efficacy and safety over 52 weeks of Bydureon, in patients treated with Bydureon for 52 weeks and in those treated with exenatide BID and switching to Bydureon after 30 weeks. Notes: In the initial 30 weeks of the study, patients either received the study drugs as initial therapy, or were on a background of metformin, a SU, a TZD or a combination of these agents After the 30-week primary endpoint, patients receiving exenatide BID were switched to Bydureon for a 22-week extension period BID, twice daily; SU, sulphonylurea; TZD, thiazolidinedione. Reference 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; SU, sulphonylurea; TZD, thiazolidinedione. Buse JB, et al. Diabetes Care 2010;33:1255–61.

23 DURATION-1: Study details (continued)
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) Background therapy None (as initial therapy) or treatment with metformin, a SU, a TZD or any combination of these agents Comparator Exenatide BID  Bydureon at Week 30 Study endpoints Change in HbA1c, FPG, weight, lipid profile and SBP Publication type Peer-reviewed publication Main talking point: The DURATION-1 clinical trial extension examined long-term efficacy and safety over 52 weeks of Bydureon, in patients treated with Bydureon for up to 5 years and in those treated with exenatide BID and switching to Bydureon after 30 weeks. Notes: In the initial 30 weeks of the study, patients either received the study drugs as initial therapy, or were on a background of metformin, a SU, a TZD or a combination of these agents After the 30-week primary endpoint, patients receiving exenatide BID were switched to Bydureon for a 3-year extension period BID, twice daily; SU, sulphonylurea; TZD, thiazolidinedione. Reference MacConell L, et al. Diabetes Metab Syndr Obes 2013;6:31–41 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

24 DURATION-1: Study details (continued)
DURATION-1: 5-year extension 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) Background therapy None (as initial therapy) or treatment with metformin, a SU, a TZD or any combination of these agents Comparator Exenatide BID  Bydureon at Week 30 Study endpoints Change in HbA1c, FPG, weight, lipid profile and SBP Publication type Congress abstract Main talking point: The DURATION-1 clinical trial extension examined long-term efficacy and safety over 52 weeks of Bydureon, in patients treated with Bydureon for up to 5 years and in those treated with exenatide BID and switching to Bydureon after 30 weeks. Notes: In the initial 30 weeks of the study, patients either received the study drugs as initial therapy, or were on a background of metformin, a SU, a TZD or a combination of these agents After the 30-week primary endpoint, patients receiving exenatide BID were switched to Bydureon for a 5-year extension period BID, twice daily; SU, sulphonylurea; TZD, thiazolidinedione. Reference MacConell L, et al. Poster presented at EASD P-980. 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 P-980.

25 Change in HbA1c (mmol/mol)
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 Bydureon BL=8.3% (67.2 mmol/mol) Exenatide BID  Bydureon BL=8.2% (66.1 mmol/mol) 6 52 48 44 40 36 33 30 26 22 18 14 10 –2.5 –2.0 –1.5 –1.0 –0.5 0.0 Time (weeks) Change in HbA1c (%) * All subjects received Bydureon –2.0% (21.9 mmol/mol) –2.0% (21.9 mmol/mol) Change from BL: –25 –20 –15 –10 –5 Change in HbA1c (mmol/mol) Main talking point: This graph shows the primary endpoint of least-squares mean change in HbA1c for the intent-to-treat population for the DURATION-1 52-week, open-label extension. Notes: The 52-week endpoint demonstrated a reduction in HbA1c with Bydureon (–2.0%) similar to that in patients who were initially treated with exenatide BID and who switched to Bydureon at 30 weeks (–2.0%) BID, twice daily. Reference Buse JB, et al. Diabetes Care 2010;33:1255–61. Figure adapted from Buse JB, et al *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 Abstract 980.

26 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 5 years3 (n=158) 3 years2 (n=194) 30 weeks1 (n=148) – 2.0 –1.5 –1.0 –0.5 0.0 Change in HbA1c (%) –1.6% (17.5 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 Change in HbA1c (mmol/mol) Randomised to Bydureon (evaluable population) Pooled population (all Bydureon completers) Main talking point: This graph shows the least-squares mean change in HbA1c for the completer population for the DURATION-1 5-year, open-label extension. Notes: In the DURATION-1 trial, all patients receiving exenatide BID switched to Bydureon at the 30-week primary endpoint and the data shown here are from the pooled populations. Final HbA1c reduction from baseline in the completer population at Year 5 was –1.6% (–17.5 mmol/mol) BID, twice daily. Reference MacConell L, et al. Diabetes Metab Syndr Obes 2013;6:31–41 Figures adapted from Drucker DJ, et al. 2008,1 MacConell L, et al. 2013,2 and MacConell L, et al 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 P-980.

27 Change in bodyweight (kg)
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 6 52 48 44 40 36 30 26 22 18 14 10 –5 –4 –3 –2 –1 Time (weeks) Change in bodyweight (kg) All subjects received Bydureon –4.1 kg –4.5 kg Change from BL: Bydureon BL=103 kg Exenatide BID  Bydureon BL=102 kg Main talking point: This graph shows a secondary endpoint of change in bodyweight for the intent-to-treat population for the DURATION-1 52-week, open-label extension.1 Notes: The secondary endpoint demonstrated a reduction in bodyweight with Bydureon at 30 weeks (–3.7 kg) similar to that with maximum daily doses of exenatide twice daily (–3.6 kg)1 Bydureon is not indicated for the treatment of obesity and weight change was a secondary endpoint in clinical trials.2 Reference Buse JB, et al. Diabetes Care 2010;33:1255–61. 2. Bydureon. Summary of product characteristics. Figure adapted from Buse JB, et al 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 Abstract 980; 3. Bydureon. Summary of product characteristics.

28 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] 5 years3 (n=158) 3 years2 (n=194) 30 weeks1 (n=148) –4 –3 –2 –1 Change in bodyweight (kg) –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) Main talking point: This graph shows the mean bodyweight reductions with Bydureon in the DURATION-1 5-year, open-label extension. Notes: In the DURATION-1 trial, all patients receiving exenatide BID switched to Bydureon at the 30-week primary endpoint and the data shown here are from the pooled populations. Final bodyweight reductions from baseline in the completer population at Year 5 were –2.8 kg1 Bydureon is not indicated for the management of obesity and weight change was a secondary endpoint in clinical trials.2 BID, twice daily. Reference MacConell L, et al. Diabetes Metab Syndr Obes 2013;6:31–41. Bydureon. Summary of product characteristics. Figures adapted from Drucker DJ, et al. 2008,1 MacConell L, et al. 2013,2 and MacConell L, et al *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 P-980; 4. Bydureon. Summary of product characteristics.

29 DURATION-2 The following slides present detailed study information and results from the DURATION-2 clinical trial of Bydureon versus sitagliptin or pioglitazone.

30 DURATION-2: Study details
DURATION-2: Primary endpoint Study details N=491 (ITT population) Randomised, double-blind, double-dummy, superiority trial Study length 26 weeks Background therapy Metformin Comparators Sitagliptin 100 mg QD Pioglitazone 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 Publication type Peer-reviewed publication Main talking point: The DURATION-2 clinical trial examined efficacy and safety of Bydureon versus sitagliptin 100 mg QD or pioglitazone 45 mg QD at the primary endpoint of Week 26. Notes: Patients were on a background therapy of metformin QD, once daily. Reference Bergenstal RM, et al. Lancet 2010;376:431–39. 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.

31 DURATION-2: Study details (continued)
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 26 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 publication Main talking point: The DURATION-2 clinical trial extension examined long-term efficacy and safety over 52 weeks of Bydureon, in patients treated with Bydureon for 52 weeks and in those treated with sitagliptin or pioglitazone and switching to Bydureon after 26 weeks. Notes: Patients were on a background of metformin After the 26-week primary endpoint, patients receiving sitagliptin or pioglitazone switched to Bydureon for a 26-week extension period Reference: Wysham C, et al. Diabet Med 2011;28:705–14. CV, cardiovascular; FPG, fasting plasma glucose; QD, once daily. Wysham C, et al. Diabet Med 2011;28:705–14.

32 Change in HbA1c from baseline (mmol/mol)
DURATION-2: Reduced HbA1c with Bydureon versus sitagliptin and pioglitazone Significant HbA1c reductions with Bydureon were sustained over 1 year, regardless of initial therapy 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) 6 52 46 40 34 30 26 22 18 14 10 –2.0 –0.5 0.0 Time (weeks) Change in HbA1c (%) 4 –1.5 –1.0 –20 –15 –10 –5 Change in HbA1c from baseline (mmol/mol) Main talking point: This graph shows the primary endpoint of change in HbA1c for the evaluable population for the DURATION-2 52-week, open-label extension trial. Notes: After the 26-week blinded period, subjects could enter an open-ended study period The study demonstrated an overall reduction in HbA1c from baseline with Bydureon (–1.5% [–16.4 mmol/mol]) similar to that in patients treated with sitagliptin  Bydureon (–1.21% [–13.2 mmol/mol]) or pioglitazone  Bydureon (–1.30% [–14.2 mmol/mol]) Patients in the sitagliptin group experienced significant reductions in HbA1c after switching to Bydureon at Week 26 (–0.31% [–3.4 mmol/mol]) Reference Wysham C, et al. Diabet Med 2011;28:705–14. 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.

33 Change in bodyweight (kg)
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 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)† 6 52 46 40 34 30 26 22 18 14 10 –3 –2 2 3 5 Time (weeks) Change in bodyweight (kg) 4 –1 1 Open-ended period Bydureon, BL=90 kg Sitagliptin  Bydureon, BL=86 kg Pioglitazone  Bydureon, BL=86 kg Main talking point: This graph shows a secondary endpoint of change in bodyweight for the evaluable population for the DURATION-2 52-week, open-label extension trial.1 Notes: The study demonstrated an overall reduction in bodyweight from baseline in patients receiving Bydureon (–1.6 kg) or sitagliptin  Bydureon (–1.9 kg)1 Patients receiving pioglitazone achieved weight reductions of –3.0 kg after switching to Bydureon at Week 26; the overall weight change from baseline at Week 52 was –0.2 kg2 Bydureon is not indicated for the treatment of obesity and weight change was a secondary endpoint in clinical trials.2 References Wysham C, et al. Diabet Med 2011;28:705–14. Bydureon. Summary of product characteristics. 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.

34 DURATION-3 The following slides present detailed study information and results from the DURATION-3 clinical trial of Bydureon versus insulin glargine.

35 DURATION-3: Study details
DURATION-3: Primary endpoint Study details N=456 (ITT population) Open-label, randomised, parallel study Study length 26 weeks 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 Publication type Peer-reviewed publication Main talking point: The DURATION-3 clinical trial examined efficacy and safety of Bydureon versus insulin glargine at the primary endpoint of Week 26. Notes: Patients were on a background therapy of metformin ± SU SU, sulphonylurea. Reference Diamant M, et al. Lancet 2010;375:2234–43. 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.

36 DURATION-3: Study details (continued)
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 Background therapy Metformin ± SU 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 Publication type Peer-reviewed publication Main talking point: This DURATION-3 clinical trial interim analysis at 84 weeks compared the efficacy and safety of Bydureon with insulin glargine. Notes: Patients were on a background of metformin ± SU SU, sulphonylurea. Reference Diamant M, et al. Diabetes Care 2012;35:683–9. 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.

37 DURATION-3: Study details (continued)
DURATION-3: 3-year extension 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 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 Main talking point: This DURATION-3 clinical trial extension compared the efficacy and safety of Bydureon with insulin glargine over 3 years. Notes: Patients were on a background of metformin ± SU SU, sulphonylurea. Reference Trautmann M. Presented at ADA 2013:67-OR. 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.

38 DURATION-3: Reduced HbA1c with Bydureon versus basal insulin at the 84-week interim analysis
Bydureon-treated patients experienced significantly greater HbA1c reductions at 84 weeks than those treated with insulin glargine 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: 84 72 60 48 36 26 22 18 14 8 0.5 6.0 7.0 8.0 HbA1c (%) Time (weeks) * 5.5 45 65 HbA1c (mmol/mol) 55 50 Main talking point: This graph shows the primary endpoint of change in HbA1c for the intent-to-treat population for the DURATION-3 clinical trial interim analysis at 84 weeks. Notes: The study demonstrated an overall reduction in HbA1c from baseline with Bydureon (–1.2% [–13.1 mmol/mol]) that was significantly greater than insulin glargine (–1.0% [–10.9 mmol/mol]) Reference Diamant M, et al. Diabetes Care 2012;35:683–9. Graph showing data for the intent-to-treat population. *p<0.05; †p= BL, baseline. Diamant M, et al. Diabetes Care 2012;35:683–9.

39 DURATION-3: Reduced HbA1c with Bydureon versus basal insulin sustained over 3 years
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 –1.5 –1.0 –0.5 0.0 Change in HbA1c from baseline (%) –1.0%* (–10.9 mmol/mol) Bydureon –0.8% (–8.7 mmol/mol) Insulin glargine BL=8.3% (67.2 mmol/mol) BL=8.3% (67.2 mmol/mol) –15 –10 –5 Change in HbA1c from baseline (mmol/mol) Main talking point: This graph shows the primary endpoint of change in HbA1c for the intent-to-treat population for the DURATION-3 clinical trial 3-year extension study. Notes: The study demonstrated an overall reduction in HbA1c from baseline with Bydureon (–1.0% [–10.9 mmol/mol]) that was significantly greater than insulin glargine (–0.8% [–8.7 mmol/mol]) Reference Trautmann M. Presented at ADA 2013:67-OR. 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.

40 Change in bodyweight (kg)
DURATION-3: Weight change with Bydureon versus basal insulin at the 84-week interim analysis Treatment with Bydureon resulted in significant weight loss instead of weight gain with insulin glargine at 84 weeks1 Time (weeks) * +2.4 ± 0.2 kg –2.1 ± 0.2 kg† 84 72 60 48 36 26 22 18 14 8 1 –4 –2 2 4 Change in bodyweight (kg) Bydureon, BL=91.2 kg (n=233) Insulin glargine, BL=90.6 kg (n=223) Change from BL: Main talking point: This graph shows a secondary endpoint of change in bodyweight for the intent-to-treat population for the DURATION-3 clinical trial interim analysis at 84 weeks.1 Notes: The study demonstrated an overall reduction in bodyweight from baseline with Bydureon (–2.1 kg), compared with weight gain with insulin glargine (+2.4 kg)1 Bydureon is not indicated for the treatment of obesity and weight change was s secondary endpoint in clinical trials.2 References Diamant M, et al. Diabetes Care 2012;35:683–9. Bydureon. Summary of product characteristics. Graph showing data for the intent-to-treat population.1 *p<0.05; †p< 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.

41 Change in HbA1c from baseline (%)
DURATION-3: Weight change* with Bydureon versus basal insulin sustained over 3 years Reductions in bodyweight were sustained over 3 years with Bydureon whilst patients in the insulin glargine group experienced significant weight gain*1 –3 –2 2 Change in HbA1c from baseline (%) –2.49 kg* Bydureon +2.01 kg Insulin glargine BL=8.3% –1 1 3 Main talking point: This graph shows a secondary endpoint of change in bodyweight for the intent-to-treat population for the DURATION-3 clinical trial 3-year extension study.1 Notes: The study demonstrated an overall reduction in bodyweight from baseline with Bydureon (–2.49 kg), compared with weight gain with insulin glargine (+2.01 kg)1 Bydureon is not indicated for the treatment of obesity and weight change was s secondary endpoint in clinical trials.2 References Trautmann M. Presented at ADA 2013:67-OR. Bydureon. Summary of product characteristics. 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.

42 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 50 70 20 30 60 40 10 Bydureon 68% Patients achieving reductions in HbA1c and bodyweight (%) Insulin glargine 34% Main talking point: This graph shows the proportion of patients achieving a dual goal of both HbA1c reductions and weight loss in the DURATION-3 clinical extension at 3 years.1 Bydureon is not indicated for the treatment of obesity and weight change was s secondary endpoint in clinical trials.2 References Trautmann M. Presented at ADA 2013:67-OR. Bydureon. Summary of product characteristics. Graph adapted from Trautmann M, 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.

43 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 Metformin background Patients reporting minor hypoglycaemia (%) 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 Main talking point: This slide represents the incidence of treatment-emergent hypoglycaemia by background therapy in the DURATION-3 trial at the 84-week planned interim analysis.1 Notes: The risk of hypoglycaemia with Bydureon was less than with insulin glargine1,2 Incidence of minor hypoglycaemia with Bydureon was low versus insulin glargine and was related to the concomitant use of an SU agent1 When Bydureon is added to SU therapy, a reduction in the dose of SU should be considered to reduce the risk of hypoglycaemia.2 SU, sulphonylurea. References Diamant M, et al. Lancet 2010;375:2234–43. Bydureon. Summary of product characteristics. Graph adapted from Diamant et al. Diabetes Care *p< 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.

44 Hypoglycaemia with GLP-1 receptor agonists
Expert sound bite Placeholder for video 1Div. Gwen Hall: Hypoglycaemia with GLP-1 receptor agonists

45 Change in CV markers with Bydureon
Evidence from DURATION-1 CV, cardiovascular.

46 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 Population and parameter Baseline (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 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 Main talking point: In a pooled analysis of the DURATION trials, significant improvements in blood pressure were observed in patients treated with Bydureon.1 Notes: This was a post hoc pooled analysis of the ITT populations of patients taking Bydureon in the 6 DURATION trials1 Note that the pooled analysis included DURATION-4,1 which was a monotherapy study. Bydureon is not indicated in Europe as first-line monotherapy in patients uncontrolled on diet and exercise alone.2 ITT, intent-to-treat. References Grimm M, et al. Postgrad Med 2013;125:46–57. 2. Bydureon. Summary of product characteristics. 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.

47 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 Randomised to Bydureon (ITT population) Pooled population (completer population) 1 –1 –2 –3 –4 –5 Change in BP (mmHg) SBP Week 301 Year 53 +0.6 mmHg –4.7 mmHg –2.1 mmHg –1.6 mmHg –1.7 mmHg –2.0 mmHg* Year 32 n=194 DBP Year 32 n=129 Baseline 128 129 78 Main talking point: Blood pressure improvements were observed in patients treated with Bydureon for up to 5 years. BID, twice daily; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol. Reference Buse JB, et al. Diabetes Care. 2010;33:1255–61. Figures adapted from Drucker DJ, et al. 2008,1 MacConell L, et al. 2013,2 and MacConell L, et al *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 P-980.

48 DURATION-1: Improvements in plasma lipids over 5 years with Bydureon
In the DURATION-1 5-year extension study, improvements from baseline in plasma lipids were observed with Bydureon treatment1–3 0.0 –0.1 –0.2 –0.3 –0.4 Change from BL (mmol/L) Total cholesterol Week 30*1 (n=148) Year 5†3 (n=158) –0.31 mmol/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 –0.2 –0.3 Change from BL (mmol/L) LDL-C Week 30*1 (n=148) Year 5†3 (n=158) –0.25 mmol/L –0.13 mmol/L –0.18‡ mmol/L Year 3†2 (n=194) B=2.37 B=2.5 BL=2.4 0.1 0.0 –0.1 Change from BL (mmol/L) HDL-C Week 30*1 (n=148) Year 5†3 (n=158) +0.06 mmol/L –0.02 mmol/L +0.03 mmol/L Year 3†2 (n=194) BL=1.14 BL=1.2 –5 –10 –15 Change from BL (%) Triglycerides Week 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 Main talking point: Plasma lipid improvements (total cholesterol, LDL-C, HDL-C and triglycerides) were observed in patients treated with Bydureon for up to 5 years. Notes: Triglyceride data are reported as a percent change from baseline due to a non-normal distribution of the data. These changes were clinically significant, but a statistical comparison and p values are not available HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol. References Drucker DJ, et al. Lancet 2008;372:1240–50. MacConell L, et al. Diabetes Met Synd Obes 2013;6:31–41. MacConell L, et al. Poster presented at EASD P-980. Randomised to Bydureon (ITT population) Pooled population (completer population) Figures adapted from Drucker DJ, et al. 2008,1 MacConell L, et al. 2013,2 and MacConell L, et al *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 P-980.

49 Bydureon safety and tolerability
Main talking point: The following slides detail the safety and tolerability of Bydureon.

50 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 Patients experiencing minor hypoglycaemia (%) 50 70 20 30 60 40 10 3% n=918 16% n=461 No concomitant SU use Main talking point: This slide represents the incidence of treatment-emergent hypoglycaemia with Bydureon by background therapy in a post-hoc analysis of the DURATION clinical trial programme.1 Notes: Incidence of minor hypoglycaemia with Bydureon was low and was related to the concomitant use of an SU agent1 The data shown are from a post-hoc analysis of the six studies in the DURATION clinical trial programme, which comprised six randomised, comparator-controlled studies (duration 24–30 weeks) was designed to assess the efficacy, safety and tolerability of Bydureon compared with common therapies used in patients with Type 2 diabetes1 Analyses were conducted on pooled data from the ITT population (N=1379)2 The DURATION-4 clinical trial of BYDUREON monotherapy versus 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 When Bydureon is added to SU therapy, a reduction in the dose of SU should be considered to reduce the risk of hypoglycaemia.2 ITT, intent-to-treat; SU, sulphonylurea. References Grimm M, et al. Postgrad Med 2013;125:47–57. Bydureon. Summary of product characteristics. Graph adapted from Grimm et al. Postgrad Med 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.

51 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.

52 System organ class/adverse reaction terms Frequency of occurrence*
Very common and common adverse reactions reported with Bydureon in clinical trials and spontaneous reports 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 distension Eructation Flatulence† Skin and subcutaneous tissue disorders Hyperhidrosis‡ General disorders and administration site conditions Injection-site pruritus Fatigue† Injection-site erythema Injection-site rash Somnolence Asthenia‡ Feeling jittery‡ Main talking point: Bydureon has a favourable adverse event profile and is generally well tolerated. Notes: The majority of adverse reactions observed with Bydureon in clinical trials and from post-marketing experience were gastrointestinal in nature (nausea, vomiting, diarrhoea and constipation); were mild to moderate; and rarely led to discontinuation Reference Bydureon. Summary of product characteristics. *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.

53 System organ class/adverse reaction terms Frequency of occurrence
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§ Main talking point: Some other less common adverse events also occurred with Bydureon in clinical trials and from post-marketing experience. Reference 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.

54 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 Incidence of nausea (%) 100 40 60 80 20 0–30 30–60 60–90 90–120 120–150 150–180 180–212 Weeks Main talking point: As with other GLP-1 receptor agonists, Bydureon is frequently associated with nausea.1–4 Notes: Patients will usually find that nausea is mild to moderate and lessens over time1 If nausea is intolerable, patients should be encouraged to speak to their healthcare professional who will be able to help them manage their symptoms GLP-1, glucagon-like peptide-1. References Bydureon. Summary of product characteristics. Byetta. Summary of product characteristics. Victoza. Summary of product characteristics. Lyxumia. Summary of product characteristics. Figure adapted from Maggs D, et al 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 Presentation #4; 6. Best JH, et al. Diabet Med 2009;26:722–8.

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

56 Handling injection-site reactions that may occur with Bydureon treatment
Injection-site reactions versus bumps Injection-site 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 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 Size of bump Main talking point: Small injection-site nodules are known properties of the microsphere technology.1,2 Notes: Small subcutaneous injection-site nodules were observed frequently and are an expected property of the microsphere delivery system1,2 These individual small bumps were mostly asymptomatic, did not interfere with study participation, and resolved over 4–8 weeks1 References Bydureon. Summary of product characteristics. DeYoung MB, et al. Diabetes Technol Ther 2011;13:1145–54. Bydureon. Summary of product characteristics.

57 Bydureon injection-site bumps
Expert sound bite Placeholder for video 1Dvi. Professor Kamlesh Khunti: Bydureon injection-site bumps

58 Contraindications and special warnings and precautions
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 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 disease Not recommended. Main talking point: This slide lists the contraindications and warnings and precautions for Bydureon, as stated in the prescribing information. CrCL, creatinine clearance. Bydureon. Summary of product characteristics. 58

59 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 is 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 have not been studied. The concurrent use of Bydureon and exenatide twice daily 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. Main talking point: This slide continues to list the warnings and precautions for Bydureon, as stated in the prescribing information. GLP-1, glucagon-like peptide-1. Bydureon. Summary of product characteristics. 59

60 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 derivatives A 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 inhibitors Concomitant use with exenatide was not associated with consistent changes in lipid profiles. Lipid profiles should be monitored as appropriate. Main talking point: This slide lists the drug interactions for Bydureon, as stated in the prescribing information. AUC, area under curve; BID, twice daily; INR, international normalised ratio. Bydureon. Summary of product characteristics. 60

61 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 –2.0 –0.5 0.0 Change in HbA1c (%) –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 –15 –10 –5 Change in HbA1c (mmol/mol) Main talking point: Some patients may develop antibodies to exenatide following treatment with Bydureon. The presence of antibodies is not predicative of glycaemic control for an individual patient.1 Notes: The development of antibodies is an expected response to the potentially immunogenic properties of protein and peptide pharmaceuticals1 In most patients who develop anti-exenatide antibodies, titres diminish over time1 Patients who developed anti-exenatide antibodies tend to have more injection-site reactions (e.g. redness of skin and itching), but otherwise have similar rates and types of adverse events as those without anti-exenatide antibodies1 The presence of antibodies caused a slightly lesser HbA1c decrease with Bydureon2 References Bydureon. Summary of product characteristics. Fineman MS, et al. Diabetes Obes Metab 2012;14:546–54. 1. Bydureon. Summary of product characteristics; 2. Fineman MS, et al. Diabetes Obes Metab 2012;14:546–54.

62 Bydureon dosing, administration and initiation

63 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 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 Main talking point: Bydureon is prescribed in a single-dose kit that contains everything patients need to administer a once-weekly injection of Bydureon. Administration is straightforward: Patients need to connect the parts, shake to mix the medicine and inject for for continuous glycaemic control. Reference Bydureon. Summary of product characteristics. *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.

64 Flexible dosing with Bydureon
Expert sound bite Placeholder for video 1Dvii. Professor Kamlesh Khunti: Flexible dosing with Bydureon

65 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.

66 Tips for injecting Bydureon
Expert sound bite Placeholder for video 1Dviii. Gwen Hall: Tips for injecting Bydureon

67 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 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 Main talking point: A usability study of the Bydureon device found that most people were able to prepare and deliver a dummy injection of Bydureon using just the instructions for use provided with the kit. Notes: The usability study consisted of 102 subjects with Type 2 diabetes. Its purpose was to evaluate the effectiveness of the ‘Instructions for user’ in training patients to prepare and deliver a dose of Bydureon in the absence of any other educational support The study population was aged between 21–75 years, with 78% injection naïve, 22% current exenatide BID users, 12% left-handed, 79% required visual assistance (glasses or contact lenses) and 21% reported physical limitations (5% neuropathy, 8% hand weakness and 8% arthritis) Subjects were given a single-dose kit and asked by a facilitator to use the instructions for use and prepare a dummy dose for injection into an injection ball. The facilitator could not answer any questions or give further support, but participants were permitted to contact a simulated customer support centre for specific questions Participants’ ability to complete the steps was assessed by the facilitator, which was supplemented by feedback from participants in a standardised questionnaire More than 90% of participants reported confidence in their ability to prepare and deliver the injection at home with access to only the ‘Instructions for user’ Around 85% of participants found the ‘Instructions for user’ easy to use Completion success was slightly affected by physical and visual limitations or requirement for visual correction. Age did not influence participants’ ability to successfully compete the task BID, twice daily. Reference Lorenzi G, et al. Clin Diabetes 2010;28:157–62. Adapted from Lorenzi G, et al. Clin Diabetes 2010;28:157–62.

68 Patients suitable for Bydureon
Expert sound bite Placeholder for video 1Dix. Professor Kamlesh Khunti: Patients suitable for Bydureon

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 doses1,2 HbA1c reductions Over time1,2 Feeling less hungry and eating less Some weight loss* *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.

70 Bydureon benefits; patient expectations and education
Expert sound bite Placeholder for video 1Dx. Gwen Hall: Bydureon benefits; patient expectations and education

71 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 *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.

72 Explaining Bydureon to patients and setting expectations
Expert sound bite Placeholder for video 1Dxi. Gwen Hall: Explaining Bydureon to patients and setting expectations

73 Patient treatment adherence and education
Expert sound bite Placeholder for video 1Dxii. Professor Kamlesh Khunti: Patient treatment adherence and education

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

75 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 Main talking point: Bydureon provides powerful efficacy with the added benefit of weight loss, in a single weekly injection that can easily fit into a patient’s life. *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 P-980; 2. Bydureon. Summary of product characteristics; 3. Lorenzi G, et al. Clin Diabetes 2010;28:157–62.

76 Bydureon patient successes
Expert sound bite Placeholder for video 1Dxiii. Gwen Hall: Bydureon patient successes


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