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Bydureon (exenatide once-weekly) Scientific slides: GLP-1 receptor agonists and the discovery of exenatide GLP-1, glucagon-like peptide-1. Developed with the guidance and approval of an independent international editorial committee Prescribing information can be found at the end of this slide deck. Date of approval: March 2015 | Date of expiry: March 2016 Approval code: 675,057.01

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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 All graphs have been created in PowerPoint to enable easy amends and translation HbA 1c 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.

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Executive summary This slide deck covers the following topics and contains speaker notes to assist presentation: 1.Introduction to Type 2 diabetes Unmet needs and barriers to treatment Epidemiology of Type 2 diabetes Barriers to treatment (weight gain, hypoglycaemia, adherence to treatment) The Type 2 diabetes treatment pathway and individualised care The place of GLP-1 receptor agonists and insulin in the treatment pathway 2.GLP-1 receptor agonists and the discovery of exenatide GLP-1 mechanism of action and the incretin effect The discovery of exenatide, the first GLP-1 receptor agonist to receive marketing authorisation

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What is GLP-1? GLP-1 is an incretin hormone that is secreted by the L-cells in the gut 1 Secreted in a nutrient-dependent manner 1 Exerts multiple glucoregulatory properties 1 Figure adapted from Drucker DJ, et al. 2006, 1 Larsson H, et al. 1997, 2 Quddusi S, et al. 2003, 3 and Flint A, et al. 1998. 4 GLP-1, glucagon-like peptide-1. 1. Drucker DJ. Cell Metab 2006;3:15365; 2. Larsson H, et al. Acta Physiol Scand 1997;160:41322; 3. Quddusi S, et al. Diabetes Care 2003;26:791 8; 4. Flint A, et al. J Clin Invest 1998;101:51520. Fasting stateFed state Suppresses glucagon secretion decreased hepatic glucose production 2 Suppresses postprandial glucagon secretion decreased hepatic glucose production 2 Slows gastric emptying 1 Stimulates glucose-dependent insulin secretion 1 Improves first-phase insulin response 3 Reduces appetite and food intake 4 Slide is animated

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The way in which oral glucose elicits a greater plasma insulin response than IV glucose is referred to as the incretin effect, which is reduced in patients with Type 2 diabetes 1 The incretin effect is diminished in Type 2 diabetes *p0.05 to the respective value after the oral load. IV, intravenous. Nauck M, et al. Diabetologia 1986;29:4652. Control 0101 0202 60 120 180 0 20 40 60 80 Time (min) Insulin (mU/L) * * * * * * * Oral glucose IV glucose Type 2 diabetes 0101 0202 60 120 180 0 20 40 60 80 Time (min) Insulin (mU/L) * * * Oral glucose IV glucose

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The production of GLP-1 is diminished in people with Type 2 diabetes *p