AstraZeneca's Xigduo XR (dapagliflozin and metformin hydrochloride extended-release), a once-daily fixed-dose combination, has been approved by China's National Medical Products Administration (NMPA) for the treatment of adults with type-2 diabetes (T2D) as an adjunct to diet and exercise to improve glycaemic control.

Xigduo XR combines two anti-hyperglycaemic agents with complementary mechanisms of action: dapagliflozin (trade name, Forxiga), a sodium-glucose cotransporter 2 (SGLT2) inhibitor, which has been approved in China for the treatment of adults with T2D, heart failure with reduced ejection fraction (HFrEF) and chronic kidney disease (CKD), and metformin hydrochloride (HCl) extended release, a biguanide, in a once-daily oral tablet. It is the only fixed-dose combination of this kind to be approved in China and provides a first-line treatment option that can improve glycaemic control in T2D patients.

Ruud Dobber, Executive Vice President, BioPharmaceuticals Business Unit, AstraZeneca said: "People living with type-2 diabetes often have comorbidities such as heart failure and chronic kidney disease, leading to cardiorenal events which are the primary causes of death and hospitalisation in this patient population. There is a need for effective and innovative therapies that can both lower the occurrence of these events and also help improve treatment adherence, which often undermines glycaemic control. Today's welcome approval reinforces SGLT2 inhibitors and metformin as foundational treatments for type-2 diabetes patients in China and represents an important step forward in better management of this condition."

There are approximately 129 million people living with T2D in China[1] and T2D accounts for more than 90% of the overall population with diabetes.[2] Patients with T2D often have poor  glycaemic control, with 60% having blood glucose levels that do not reach target ranges.[3] Sustained high levels of blood glucose can cause damage to many of the body's organs, leading to life-threatening health complications such as cardiovascular disease and kidney damage.[4  ]Low medication adherence due to complex drug regimens can contribute to the low glycaemic control, with over half of patients with T2D needing to take between 3-6 tablets per day.[5]

The approval by China's NMPA was based on a local bioequivalence study and supported by the global diabetes program for Xigduo XR, which provided clinical evidence for the efficacy and safety profile of dapagliflozin and metformin immediate-release (IR) or XR tablets in patients inadequately controlled on metformin.

Xigduo XR is approved in the US, Australia and other regions.

Notes

T2D
T2D is a chronic disease characterised by pathophysiologic defects leading to elevated glucose levels, or hyperglycaemia.[4 ]Over time, this sustained hyperglycaemia contributes to further progression of the disease.[4 ]The prevalence of diabetes is projected to reach 783 million by 2045.[4] T2D accounts for more than 90% of the overall population with diabetes in China.[2] Significant unmet medical need still exists, as many patients have poor blood sugar control and low medication adherence.[4,5]

Xigduo XR
Xigduo XR is the first once-daily combination tablet of dapagliflozin, an SGLT2 inhibitor, and metformin, a biguanide, indicated as an adjunct therapy to diet and exercise to improve glycaemic control in adults with T2D mellitus when treatment with dapagliflozin and metformin is appropriate.

Forxiga
Forxiga (dapagliflozin) is a first-in-class, oral, once-daily SGLT2 inhibitor. Research has shown Forxiga's efficacy in preventing and delaying cardiorenal disease, while also protecting the organs - important findings given the underlying links between the heart, kidneys andpancreas.[6-8] Damage to one of these organs can cause the other organs to fail, contributing to leading causes of death worldwide, including T2D, HF and chronic kidney disease (CKD).[9-11]

AstraZeneca in CVRM
Cardiovascular, Renal and Metabolism (CVRM), part of BioPharmaceuticals, forms one of AstraZeneca's main disease areas and is a key growth driver for the Company. By following the science to understand more clearly the underlying links between the heart, kidneys and pancreas, AstraZeneca is investing in a portfolio of medicines for organ protection and improving outcomes by slowing disease progression, reducing risks and tackling co-morbidities. The Company's ambition is to modify or halt the natural course of CVRM diseases and potentially regenerate organs and restore function, by continuing to deliver transformative science that improves treatment practices and CV health for millions of patients worldwide.

AstraZeneca
AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Disease, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit astrazeneca.com (http://www.astrazeneca.com/) and follow the Company on Twitter @AstraZeneca (http://www.twitter.com/AstraZeneca).

Contacts
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References

1. Li Y, et al. Prevalence of diabetes recorded in mainland China using 2018 diagnostic criteria from the American Diabetes Association: national cross sectional study. BMJ. 2020; 369-997.
2. Weng J, et al. Standards of care for type 2 diabetes in China. Diabetes Metab Res Rev. 2016; 32(5):442-58.
3. Yu Xu, et al. Prevalence and Control of Diabetes in Chinese Adults. JAMA. 2013;310(9):948-958.
4. International Diabetes Federation [Internet]. IDF Diabetes Atlas Tenth Edition 2021. [cited 2023 May 24]. Available from: https://diabetesatlas.org/idfawp/resource-files/2021/07/IDF_Atlas_10th_Edition_2021.pdf
5. Blüher M, et al. Pill Burden in Patients With Type 2 Diabetes in Germany: Subanalysis From the Prospective, Noninterventional PROVIL Study. 2015; 33(2): 55-61.
6. McMurray JJV, et al. Dapagliflozin in patients with heart failure and reduced ejection fraction. N Engl J Med. 2019;381(21):1995-2008.
7. Heerspink HJL, et al. Dapagliflozin in patients with chronic kidney disease. N Engl J Med. 2020;383(15):1436-1446.
8.  Wiviott SD, et al; for the DECLARE-TIMI 58 Investigators. Dapagliflozin and cardiovascular outcomes in type 2 diabetes [article and supplementary appendix]. N Engl J Med. 2019;380(4):347-357.
9.  Mayo Clinic [Internet]. Heart failure [cited 2023 May 24]. Available from: https://www.mayoclinic.org/diseases-conditions/heart-failure/symptoms-causes/syc-20373142.
10. Centers for Disease Control and Prevention (CDC) [Internet]. A snapshot: Diabetes in the United States [cited 2023 May 24]. Available from: https://www.cdc.gov/diabetes/library/socialmedia/infographics/diabetes.html.
11. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [Internet]. Heart disease & kidney disease [cited 2023 May 24]. Available from: https://www.niddk.nih.gov/health-information/kidney-disease/heart-disease.