| Source: AstraZeneca PLC

Study showed patients inadequately controlled on metformin achieved
statistically significant reduction of HbA1c with the combination of saxagliptin
and dapagliflozin versus either agent alone

Overall rates of adverse events similar between the three treatment groups, and
most were reported as mild or moderate in intensity. Improvements in glycaemic
control achieved without increased risk of hypoglycaemia with more patients
reaching goal HbA1c levels of less than 7% and were associated with body weight

AstraZeneca will commence a Phase III trial for dapagliflozin in patients with
Type 1 diabetes in 2014

AstraZeneca today announced results from a Phase III study evaluating the
investigational combination of saxagliptin/dapagliflozin as a dual add-on
therapy in adult patients with type 2 diabetes who were inadequately controlled
on metformin.

Results from the combination study found that patients treated with
saxagliptin/dapagliflozin plus metformin achieved significantly greater
reductions in HbA1c versus either agent alone plus metformin at 24 weeks, with
an adjusted mean change from baseline HbA1c of -1.47% in the
saxagliptin/dapagliflozin combination group compared to -0.88% in the
saxagliptin group and -1.20% in the dapagliflozin group. More patients in the
saxagliptin/dapagliflozin combination group (41%) achieved goal HbA1c levels of
less than 7% compared to patients in the saxagliptin (18%) and dapagliflozin
(22%) groups.[i]

The saxagliptin/dapagliflozin combination group achieved a significantly greater
adjusted mean reduction from baseline in two-hour postprandial glucose (PPG)
versus the saxagliptin group, but not the dapagliflozin group. The adjusted mean
reduction in fasting plasma glucose (FPG) was greater in the
saxagliptin/dapagliflozin combination group (-38 mg/dL) than the saxagliptin
group (-14 mg/dL), but similar to the dapagliflozin group (-32 mg/dL). In this
study, overall rates of adverse events, including hypoglycaemia, were similar
between the three treatment groups, and most were reported as mild or moderate
in intensity.

"Diabetes is a progressive disease in which nearly half of patients do not
achieve their HbA1c goals. Despite the standard sequential use of existing
therapies, there is a need for new and earlier therapeutic approaches that
provide more robust HbA1c lowering," said lead investigator Julio Rosenstock,
MD, director of the Dallas Diabetes and Endocrine Center at Medical City and
clinical professor of medicine at the University of Texas Southwestern Medical
School, Dallas, Texas. "What we've observed in this trial is when the two
independent mechanisms of action of saxagliptin and dapagliflozin are used in
combination, significant reductions in HbA1c associated with weight loss are
achieved in patients not adequately treated with metformin alone, and more
patients reached the HbA1c target goal without increased risk of hypoglycaemcia
while maintaining a similar safety profile to the individual monotherapies."

"The results for the combination of saxagliptin and dapagliflozin demonstrate
our continued commitment to meeting the needs of patients with type 2 diabetes
by working to understand how these two medicines with independent mechanisms of
action may be used together to help more patients achieve their treatment
goals," said Briggs Morrison, Executive Vice President, Global Medicines
Development & Chief Medical Officer, AstraZeneca.

This 24-week, Phase III, multi-center, randomised, double-blind, active
-controlled, parallel-group trial was designed to evaluate the efficacy and
safety of the combination of saxagliptin/dapagliflozin as dual add-on therapy in
adult patients with type 2 diabetes with inadequate glycaemic control on
metformin. The primary endpoint was mean change in HbA1c from baseline to week
24. Secondary endpoints included mean change from baseline in two-hour PPG
during a liquid meal test, FPG, body weight at week 24 in the
saxagliptin/dapagliflozin combination group versus the saxagliptin group, and
the proportion of patients who achieved glycaemic response (defined as HbA1c <

The study included 534 adult patients with type 2 diabetes (aged ≥ 18 years)
with inadequate glycaemic control (HbA1c ≥ 8% and ≤ 12%) who were receiving
metformin extended-release (≥ 1,500 mg per day). Patients were randomised 1:1:1
to receive the combination of saxagliptin 5 mg and dapagliflozin 10 mg added to
metformin, saxagliptin and metformin added to placebo, or dapagliflozin and
metformin added to placebo, for 24 weeks.1

Future Development of AstraZeneca Oral Anti-Diabetic Franchise

Type 1 diabetes patients are dependent on lifelong insulin injections which
present a constant risk for hypoglycaemic events and long term weight gain.
AstraZeneca will commence a Phase III trial for dapagliflozin in patients with
Type 1 diabetes in 2014.

About DPP4 inhibitors and SGLT2 inhibitors

Saxagliptin (marketed as Onglyza®) belongs to the class of medicines called DPP
-4 inhibitors, which work by increasing the activity of the incretin hormones,
increasing the release of insulin when glucose levels are elevated and reducing
the levels of sugar produced by the liver (glucagon).[ii]Dapagliflozin (marketed
as Farxiga™ in the U.S. and Forxiga® outside the U.S.) is part of a newer class
of medicines called sodium-glucose cotransporter 2 (SGLT2) inhibitors, which
remove glucose via the kidneys.

About Type 2 Diabetes

Diabetes is estimated to affect 25.8 million people in the U.S. and more than
382 million people worldwide. The prevalence of diabetes is projected to reach
more than 592 million people worldwide by 2035.[iii] Type 2 diabetes accounts
for approximately 90-95 percent of all cases of diagnosed diabetes in
adults.[iv] Type 2 diabetes is a chronic disease[v] characterised by
pathophysiologic defects leading to elevated glucose levels.[vi] Over time, this
sustained hyperglycaemia contributes to further progression of the disease.[vii]
Significant unmet needs still exist, as many patients remain inadequately
controlled on their current glucose-lowering regimen.[viii]

About AstraZeneca

AstraZeneca is a global, innovation-driven biopharmaceutical business that
focuses on the discovery, development and commercialisation of prescription
medicines, primarily for the treatment of cardiovascular, metabolic,
respiratory, inflammation, autoimmune, oncology, infection and neuroscience
diseases. AstraZeneca operates in over 100 countries and its innovative
medicines are used by millions of patients worldwide. For more information
please visit:


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[i]              Rosenstock, J., et al. "Dual Add-On Therapy in Poorly
Controlled Type 2 Diabetes on Metformin: Randomized, Double-Blind Trial of
Saxagliptin+Dapagliflozin vs Saxagliptin and Dapagliflozin Alone." American
Diabetes Association Scientific Sessions 2014. Abstract #127-LB.
[ii]             Bristol-Myers Squibb Company and AstraZeneca Pharmaceuticals
LP. July 2009. Onglyza (saxagliptin) tablets: Highlights of Prescribing
Information. Available at: Accessed
May 1, 2014.

[iii]             International Diabetes Federation. IDF Diabetes Atlas, 6th
edn., 2013. Available at: Accessed May 1,

[iv]             Centers for Disease Control and Prevention. National Diabetes
Factsheet 2011. Available at: Accessed May 1, 2014.

[v]             World Health Organization. Media Centre - Diabetes. 2011.
Available at: Accessed May
1, 2014.

[vi]             Kahn SE. The relative contributions of insulin resistance and
beta-cell dysfunction to the pathophysiology of type 2 diabetes. Diabetologia.

[vii]            Kahn SE. Clinical review 135: The importance of β-cell failure
in the development and progression of type 2 diabetes. J Clin Endocrinol Metab.

[viii]           Cheung B, Lond, Edin et al. Diabetes Prevalence and Therapeutic
Target Achievement in the United States, 1999-2006. American Journal of
Medicine. 2009;122:443-453.

13 May 2014