Supported by Virtual Poster Hall: Summary Slides Professor Stephan Matthaei Tuesday, September 15 th This Virtual Poster Hall session explores the relationship between diabetes duration and response to therapy, the effects of GLP-1 receptor agonists on both glycemic and non- glycemic endpoints, as well as the relevance of non-alcoholic fatty liver disease in insulin resistance. This content is comprised of video footage and summary slides. ATLAS Approval ID: ; Date of Preparation: September 2015; Expiry Date: September 2016

Supported by The Effect of Diabetes Duration on Response to Medication Pooled data were analysed in attempt to quantify the effect of disease duration on response to medication As expected, patients with a long duration of diabetes tended to have high baseline HbA 1c ; however, long duration of diabetes was not associated with a reduced response to exenatide twice daily or insulin, even in patients with a T2DM duration >15 years These findings were independent of baseline metformin or sulfonylurea use and suggest that patients with very high HbA 1c or patients who have had T2DM for many years, may equally benefit from treatment with GLP-1 receptor agonists GLP-1, glucagon-like peptide 1; HbA 1c ; glycated hemoglobin; T2DM, type 2 diabetes. Aronoff et al. EASD 2015; Abstract 772.

Supported by GLP-1 Agonists – Glycemic Control and Beyond A post hoc analysis of pooled data from 20 randomized trials in a sub population of patients with baselines HbA 1c ≥10%, revealed that endpoint reductions in HbA 1c were comparable between exenatide twice daily and basal insulin and numerically greater with exenatide once weekly 1 Other pooled data demonstrated that GI effects are more common with short- vs long-acting GLP-1 receptor agonists, whereas short-acting agents have more transient effects on heart rate, compared with long acting agents 2,3 Analysis in ~70,000 patients, revealed that the risk of developing pancreatic cancer was increased to similar levels for all antihyperglycemic therapies included in the study; this suggests that diabetes is a risk factor for pancreatic cancer independent of specific drug effect, yet warrants further investigation 4 GI, gastrointestinal; GLP-1, glucagon-like peptide 1; HbA 1c ; glycated hemoglobin. 1. Busch et al. EASD 2015; Abstract 771; 2. Horowitz et al. EASD 2015; Abstract 15; 3. Lorenz et al. EASD 2015; Abstract 16; 4. Thomsen et al. EASD 2015; Abstract 17.

Supported by GLP-1 Agonists – Glycemic Control and Beyond NAFLD is a growing area of interest, both its own respect, and because of its association with insulin resistance and hyperglucagonemia In a small study (N=20), patients with NAFLD had impaired suppression of glucose production in response to infused GLP-1; however, GLP-1 suppressed glucagon to a similar extent in both healthy individuals and those with NAFLD Intact preservation of glucagon control by GLP-1 in patients with NAFLD may be an important mechanism for sustaining normoglycemia GLP-1, glucagon-like peptide 1; NAFLD, non-alcoholic fatty liver disease; Junker et al. EASD 2015; Abstract 547

Supported by GLP-1 Agonists – Glycemic Control and Beyond NAFLD is a growing area of interest, both its own respect, and because of its association with insulin resistance and hyperglucagonemia In a small study (N=20), patients with NAFLD had impaired suppression of glucose production in response to infused GLP-1; however, GLP-1 suppressed glucagon to a similar extent in both healthy individuals and those with NAFLD Intact preservation of glucagon control by GLP-1 in patients with NAFLD may be an important mechanism for sustaining normoglycemia GLP-1, glucagon-like peptide 1; NAFLD, non-alcoholic fatty liver disease; Junker et al. EASD 2015; Abstract 547

Supported by Conclusion Even though patients with long diabetes duration generally have high HbA 1c, they still appear to benefit from treatment with exenatide twice daily Exenatide twice daily, has antihyperglycemic properties as well as other effects Exploring NAFLD as a therapeutic target is a growing area of research, both to treat the condition itself and also because of its association with insulin resistance GLP-1, glucagon-like peptide 1; HbA 1c ; glycated hemoglobin; NAFLD, non-alcoholic fatty liver disease