AstraZeneca presents data demonstrating progress of diabetes portfolio

AstraZeneca today announced that 86 abstracts reporting results of the company’s research and development in diabetes have been accepted for presentation at the 75th Scientific Sessions of the American Diabetes Association (ADA) in Boston, 5-9 June 2015.

86 abstracts represent significant investment in diabetes research with a focus on individualised treatment approaches
Notable late-breaker abstracts include data from a Phase III study comparing the efficacy and safety of dapagliflozin versus placebo as an add-on to saxagliptin and metformin in adults with type 2 diabetes
New real-world data from an observational, retrospective claims database study comparing the risk of hospitalisation for heart failure between DPP-4 inhibitors vs. sulfonylureas and comparing saxagliptin with sitagliptin
Data to advance understanding of the efficacy and safety of AstraZeneca’s comprehensive diabetes portfolio and the multiple diabetes-related cardiovascular risk factors

The abstracts include clinical data evaluating Forxiga® (dapagliflozin, marketed in the U.S. as Farxiga®), Bydureon® (exenatide extended-release for injectable suspension), Byetta® (exenatide) injection and Onglyza® (saxagliptin), as well as the investigational combination of saxagliptin and dapagliflozin. Among the abstracts accepted are studies evaluating long-term durability; safety and efficacy; medication adherence; and benefits and treatment effects across diverse subpopulations segmented by ethnicity and risk factors such as kidney disease and cardiovascular (CV) disease. Notable late-breaker abstracts include data from a Phase III study comparing the efficacy and safety of dapagliflozin versus placebo as an add-on to saxagliptin and metformin in adults with type 2 diabetes who had inadequate glycaemic control, including an overview of the open-label lead-in period.

“The extensive scientific data at ADA underscore our research goals to better understand the long-term effects of newer classes of medicines across different patient populations,” said Elisabeth Björk, Vice President, Head of Cardiovascular and Metabolic Diseases, Global Medicines Development, AstraZeneca. “These data further demonstrate the value of our current portfolio to help address the needs of a broad range of patients with type 2 diabetes.”

In addition to advancing clinical and scientific discussions, AstraZeneca is also presenting a number of observational and medical outcomes studies, including new real-world data from an observational, retrospective claims database study comparing the risk of hospitalisation for heart failure between DPP-4 inhibitors vs. sulfonylureas and comparing saxagliptin with sitagliptin.¹

Notable clinical and pre-clinical data being presented across key focus areas for AstraZeneca include:

Investigational new data

Study of baseline albuminuria level versus the efficacy of dapagliflozin in patients with type 2 diabetes (#108-OR, Saturday 6 June, 1:45 p.m. EDT)²
Assessment of dapagliflozin effects on albuminuria reductions in hypertensive patients with diabetes (#1176-P, Saturday 6 June, 12:30 p.m. EDT)³
Pharmacodynamic comparison of dapagliflozin in patients with type 1 or type 2 diabetes (#1174-P, Saturday 6 June, 12:30 p.m. EDT)⁴
An analysis of dapagliflozin on insulin resistance in type 2 diabetes (#1179-P, Saturday 6 June, noon EDT)⁵
Pre-clinical analysis of the effects of a GLP-1 receptor agonist/glucagon co-agonist (MEDI0382) on weight (#2119–P, Sunday 7 June, noon EDT)⁶

Data assessing combination treatments and treatment approaches in select subgroups of patients

An analysis of triple therapy with dapagliflozin versus placebo when added-on to saxagliptin plus metformin, including an overview of the open-label lead-in period (#133–LB, Sunday 7 June, noon EDT)⁷
Study determining influential factors affecting preferences for the treatment of diabetes (#206–OR, Sunday 7 June, 2:15 p.m. EDT)⁸
A study examining the addition of saxagliptin, compared to placebo,treatment with dapagliflozin and metformin in patients with type 2 diabetes with inadequate glycaemic control (#104-OR, Saturday 6 June, 1:45 p.m. EDT)⁹
A study examining the addition of dapagliflozin, compared to placebo, to treatment with saxagliptin and metformin in patients with type 2 diabetes with inadequate glycaemic control (#105-OR, Saturday 6 June, 1:45 p.m. EDT)¹⁰
Retrospective study of once-weekly exenatide treatment and adherence in elderly patients compared to other GLP-1 receptor agonists (#1144–P, Saturday 6 June, 11:30 a.m. EDT)¹¹
Comparison of one-year adherence, costs and utilisation between insured patients with type 2 diabetes initiating liraglutide or once-weekly exenatide (#1125-P, Saturday 6 June 11:30 a.m. EDT)¹²
Dapagliflozin as a treatment option for African Americans and Hispanic Adult patients with type 2 diabetes (#1217–P, Sunday 7 June, noon EDT)¹³
Saxagliptin as a treatment option for Caucasian, African Americans, Asian, and Hispanic patients with type 2 diabetes (#1248–P, Sunday 7 June, noon EDT)¹⁴
Pre-clinical assessment of interactions of low dose combinations of GLP-1 receptor and GIP on glucose control in mice (#2350–P, Sunday 7 June, noon EDT)¹⁵

Data assessing the long-term effect and durability of AstraZeneca diabetes treatments

Effect on dapagliflozin on weight over the first year of treatment through the subsequent three years (#103–OR, Saturday 6 June, 2:15 p.m. EDT)¹⁶
Study of long-term effects of once-weekly exenatide on weight gain and hypoglycaemia, compared to insulin glargine. (#1120–P, Saturday 6 June, 11:30 a.m. EDT)¹⁷
Effects of exenatide twice daily and once weekly on A1C in patients with type 2 diabetes and baseline A1C ≥10%. (#1126–P, Saturday 6 June, 11:30 a.m. EDT)¹⁸
Analysis of the use of saxagliptin and cancer risk in the SAVOR trial (#11–OR, Friday 5 June, 4:15 p.m. EDT)¹⁹

Data assessing diabetes treatments and cardiovascular outcomes in patients at high CV risk

Analysis of dapagliflozin on CV events in elderly patients with type 2 diabetes (#15–OR, Friday 5 June, 4:45 p.m. EDT)²⁰
SAVOR analysis on rates of CV risk and polyvascular disease in patients with type 2 diabetes (#56–OR, Saturday 6 June, 8:15 a.m. EDT)²¹
Analysis of long-term efficacy of dapagliflozin treatment on patients with CV disease and type 2 diabetes (#106–OR, Saturday 6 June, 3:00 p.m. EDT)²²
Results of the SAVOR trial analysing CV outcomes in African Americans receiving treatment with saxagliptin (#15-LB; Sunday 7 June, noon EDT)²³
Observational analysis comparison of the risk of hospitalization for heart failure between DPP-4 inhibitors vs. sulfonylureas and with saxagliptin vs. sitagliptin
(#164–P, Sunday 7 June, noon EDT)¹

The complete list of AstraZeneca data presentations can be accessed on the ADA website here.

About Type 2 Diabetes

Diabetes is estimated to affect 29.1 million people in the US and more than 387 million people worldwide. The prevalence of diabetes is projected to reach more than 592 million people worldwide by 2035. Type 2 diabetes accounts for approximately 90-95 percent of all cases of diagnosed diabetes in the US. Type 2 diabetes is a chronic disease characterised by pathophysiologic defects leading to elevated glucose levels. Significant unmet needs still exist, as many patients remain inadequately controlled on their current glucose-lowering regimen. It is estimated that more than half of people living with type 2 diabetes are not achieving recommended HbA1c goals based on guidelines established by professional societies and advocacy organisations for diabetes management.

About AstraZeneca in Diabetes

AstraZeneca is pushing the boundaries of science to create life-changing medicines that aim to reduce the global burden and complications of diabetes. Driven to redefine outcomes for diabetes patients, our current portfolio consists of the three newest classes of non-insulin, anti-diabetic treatments that support individualised treatment approaches: SGLT-2 inhibitors, GLP-1 receptor agonists and DPP-4 inhibitors. Our commitment to diabetes is exemplified by the depth and breadth of our global clinical research programme. This commitment is advancing understanding of the treatment effects of our diabetes medicines in broad patient populations, as well as exploring combination treatment approaches resulting in more patients achieving treatment success earlier in their disease progression. Our ambition is to reduce the long-term impact of diabetes. As a core strategic area for the company, we are focusing our research and development efforts in diverse populations and patients with significant co-morbidities, such as cardiovascular disease, heart failure, obesity, non-alcoholic steatohepatitis (NASH), and chronic kidney disease.

¹Fu, A., et al. “Observational Study Comparing the Risk of Hospitalization for Heart Failure between Dipeptidyl Peptidase inhibtors vs. Sulfonlyureas and Saxaglitpin vs Sitagliptin.” American Diabetes Association Scientific Sessions 2015. Abstract #164-LB
²Parikh, S., et al. “Dapagliflozin Efficacy is Unaffected by Baseline Albuminuria Level in Patients with Type 2 Diabetes.” American Diabetes Association Scientific Sessions 2015. Abstract #108-OR
³Lambers-Heerspink. H., et al., “Dapagliflozin Reduces Albuminuria On Top of Renin-Angiotensin System Blockade in Hypertensive Diabetic Patients.” American Diabetes Association Scientific Sessions 2015. Abstract #1176-P
⁴Tang, W., et al. “Comparison of Pharmacodynamics of Dapagliflozin in Patients With Type 1 or Type 2 Diabetes Mellitus.” American Diabetes Association Scientific Sessions 2015. Abstract #1174-P
⁵Katz, A., et al. “Dapagliflozin and Insulin Resistance in Patients With Type 2 Diabetes.” American Diabetes Association Scientific Sessions 2015. Abstract #1179-P
⁶Agoram, B., et al. “Robust Anti-Obesity and Metabolic Effects of GLP-1/Glucagon Co-Agonist Peptide in Rodents and Non-Human Primates.” American Diabetes Association Scientific Sessions 2015. Abstract #2119
⁷Mathieu, C., et al. “Triple Therapy With Dapagliflozin (DAPA) Add-on to Saxagliptin (SAXA) Plus Metformin (MET): Characterization of the Open-Label SAXA+MET Lead-in Period of a Phase 3 Trial.” American Diabetes Association Scientific Sessions 2015. Abstract #133-LB
⁸Bell, K., et al. “Most influential factors determining patient preferences for diabetes treatment.” American Diabetes Association Scientific Sessions 2015. Abstract #206-OR
⁹Matthaei, S., et al. “A Randomized, Double-Blind Trial of Saxagliptin Add-on to Dapagliflozin + Metformin.” American Diabetes Association Scientific Sessions 2015. Abstract #104-OR
¹⁰Mathieu, C., et al. “A Randomized, Double-Blind, Phase 3 Trial of Dapagliflozin Add-on to Saxagliptin + Metformin in Type 2 Diabetes.” American Diabetes Association Scientific Sessions 2015. Abstract #105-OR
¹¹Dufour, R., et al. “Real-World Adherence in Patients Aged ≥ 65 years With Type 2 Diabetes Mellitus for Exenatide QW, Liraglutide QD and Exenatide BID.” American Diabetes Association Scientific Sessions 2015. Abstract #1144-P
¹²Johnston, S., et al. “Comparison of 12-month Adherence and Healthcare Costs and Utilization Between Commercially-insured Patients with Type 2 Diabetes Mellitus Newly-initiating Liraglutide Once Daily or Exenatide Once Weekly in Real-World U.S. Clinical Practice.” American Diabetes Association Scientific Sessions 2015. Abstract #1125-P
¹³Moran, J., et al. “Efficacy and Safety of Dapagliflozin in Patients With Type 2 Diabetes: Outcomes by Race and Ethnicity.” American Diabetes Association Scientific Sessions 2015. Abstract #1217-P
¹⁴Barrett, Y., et al. “Efficacy and Safety of Saxagliptin in Patients With Type 2 Diabetes: Outcomes by Race and Ethnicity.” American Diabetes Association Scientific Sessions 2015. Abstract #1248-P
¹⁵Suckow, AT., et al. “Anti-obesity and anti-diabetic activity of combinations of GIP and GLP-1 Fc-fusion proteins in obese and diabetic mice.” American Diabetes Association Scientific Sessions 2015. Abstract 2350-P.
¹⁶Stenlof, K., et al. “Maintenance of Weight Loss with Dapagliflozin Versus Glipizide As Add-On to Metformin Over 4 Years.” American Diabetes Association Scientific Sessions 2015. Abstract #103-OR
¹⁷Trautmann, M., et al. “Three-year Efficacy and Safety of Exenatide Once Weekly: A Pooled Analysis of 3 Trials.” American Diabetes Association Scientific Sessions 2015. Abstract #1120-P
¹⁸Busch, R. et al. “Treatment of T2DM Patients with Baseline A1C ≥10% with Exenatide Twice Daily (BID), Exenatide Once Weekly (QW), or Basal Insulin: A Pooled Analysis of 20 Randomized Controlled Trials (RCTs).” American Diabetes Association Scientific Sessions 2015. Abstract #1126-P
¹⁹Leiter, L, et al. “Saxagliptin and cancer in the SAVOR Trial.” American Diabetes Association Scientific Sessions 2015. Abstract #11-OR
²⁰Gause-Nilsson, I., et al. “No Increased Risk of Cardiovascular Events With Dapagliflozin in Elderly Patients with Type 2 Diabetes Mellitus, Cardiovascular Disease and Hypertension.” American Diabetes Association Scientific Sessions 2015. Abstract #15-OR
²¹Gutierrez, A., et al. “High Cardiovascular Risk of Polyvascular Disease in Diabetes - Insights from SAVOR-TIMI.” American Diabetes Association Scientific Sessions 2015. Abstract #56-OR
²²Cefalu, W., et al. “Long-term Safety and Efficacy of Dapagliflozin in Patients with T2DM and Cardiovascular Disease.” American Diabetes Association Scientific Sessions 2015. Abstract #106-OR
²³Dagogo-Jack, S., et al. “Cardiovascular outcomes of Saxagliptin Treatment in African Americans with Type 2 Diabetes: Results from the SAVOR-TIMI 53 Trial.” American Diabetes Association Scientific Sessions 2015. Abstract #15-LB