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What are metabolic diseases?
Obesity and overweight, and type 2 diabetes affect billions of people worldwide, and are part of a growing and complex global health challenge that require an urgent response.
Our bodies convert the food we eat into energy, which can be used immediately or stored in various forms for later use, including as fat (in adipose tissue), as glycogen (in the liver and muscles), and to a lesser extent, through the protein structure in muscle tissue. We rely on a network of intricate systems to manage the use – or metabolism – of fat and sugar. These processes are essential for life, but when they go wrong, often because of hormonal or genetic issues, it can lead to serious health complications and diseases.1
When excess fat builds up in the body, it can negatively affect other organs, sometimes leading to cardiovascular, renal and metabolic diseases. These metabolic diseases, such as obesity, overweight, type 2 diabetes (T2D), dyslipidaemia, and metabolic dysfunction-associated steatohepatitis (MASH), 1 often occur together, share common risk factors, and are associated with a range of increased burden on mental and physical health.2,3
Because these conditions are interconnected, at AstraZeneca we are focusing on creating the next generation of medicines that can help tackle obesity and overweight, and also allow people to reduce and reverse weight-related disease, protecting their vital organs and long-term health.
[#obesity]
Obesity and overweight: A complex health crisis
The link between energy intake and the gut response is primarily through a gut-brain axis, where intestinal hormones and signals communicate with the brain, influencing appetite, satiety and overall energy balance.3 Dysregulation of this pathway leads to metabolic diseases such as obesity,3 a complex, chronic, relapsing disease that is estimated to affect one in eight people globally.4
Obesity and overweight is estimated to affect more than 2.5 billion adults worldwide,4 almost 60% of which are living with at least one co-occurring metabolic, heart, liver or kidney disease.5 Furthermore, weight stigma has increased by two-thirds over the past decade, with its prevalence now rivalling discrimination based on race and age.6 These factors combine to make obesity and overweight one of the most physically and emotionally taxing diseases for people to live with.
At AstraZeneca, our mission is to advance research into the next generation of targeted weight management solutions to deliver not only effective weight loss but also durable long-term weight management solutions for people living with obesity and overweight. This approach has the potential to substantially reduce disease burden and improve health outcomes for patients.
Our continued research and innovation focus is on deepening our understanding of the root causes of obesity and overweight, recognising the individual patient needs, preferences and underlying risk factors to develop next-generation treatments that deliver meaningful full-body health benefits.
[#disease-risk]
Implications of fat distribution on disease risk
Understanding fat distribution is particularly important for managing a person’s risk factors effectively, as the physical location of fat in the body influences a person’s chances of comorbidities and complications.7 The body stores most excess energy as white adipose tissue, which accumulates mainly in two places or depots:8
- Subcutaneous fat is located just beneath the skin, commonly in the arms, legs and buttock regions, and can function as a healthy energy reserve that also provides insultation. Although excessive subcutaneous fat contributes to clinical obesity and overweight, it does not carry the same health risks as visceral fat.9
- Visceral fat is found deep inside the abdominal cavity, surrounding and within internal organs such as the liver, stomach and intestines. It is highly associated with metabolic and cardiovascular diseases, including type 2 diabetes, heart disease and inflammation.9
Excess fat is remarkably active and can become dysfunctional.
- Visceral fat releases fatty acids, hormones such as leptin, and inflammatory molecules that affect appetite, insulin sensitivity and can lead to inflammation.10
- Dysfunctional fat tissue can contribute to chronic inflammation, tissue fibrosis, disrupted hormone signalling and impaired cellular energy production, affecting the heart, liver, kidneys, blood vessels, and the brain.12,13
This is why AstraZeneca is developing a range of therapies that can help reduce excess fat while protecting what matters, like heart, kidney, liver, and muscle function.
[#addressing-diabetes]
Addressing the broader impact of type 2 diabetes
Diabetes is a complex and serious metabolic condition, with significant physical and psychological burden for patients that can harm their quality of life.14 It extends beyond blood sugar regulation, fuelling diseases of the heart, blood vessels, liver, and kidneys.15,16
Driven by increasing urbanisation, an ageing population, decreasing physical activity and increasing prevalence of obesity and overweight, the number of adults living with diabetes is expected to almost double by 2050 – due to affect 852.5 million people worldwide.17 Almost 90% of newly-diagnosed people with type 2 diabetes (T2D) are living with either overweight or obesity,18 and both are key drivers of the condition – in both obesity and overweight, insulin resistance reduces the body’s ability to regulate blood sugar levels.19
Diabetes is one of the leading causes of death globally, and without proper management it can eventually lead to life-threatening complications including blindness, kidney failure, heart attacks, coma, stroke and lower limb amputation.20,21 Although guidelines have clear recommendations for optimising T2D therapy, many people living with the condition struggle to achieve their treatment goals.22,23 There remains a need for management options that are accessible, meet patients’ individual goals, and help to manage other long-term chronic conditions, which includes preventing progression and development of interrelated diseases while minimising impact on patients’ daily lives.24,25
Our continued focus on the bigger picture of diabetes and related complications is more important than ever. With strong heritage in diseases of the heart, blood vessels, liver and kidneys, AstraZeneca’s rigorous scientific research is committed to delivering diabetes medications that treat both the root causes of the condition and its related complications. Through research partnerships, we are also advancing the development of next-generation therapies for type 1 diabetes (T1D), aiming to slow disease progression and improve outcomes for people living with this lifelong chronic condition.
[#mash]
Addressing MASH’s complexity with targeted therapeutics
Metabolic associated steatohepatitis (MASH) is a liver disease where excess fat in the liver triggers inflammation and cell damage.26 It is rapidly emerging as a leading cause of chronic liver disease, with up to 350 million diagnoses expected by 2030.27 People with MASH face higher risk of T2D and heart disease,28 and can develop liver cirrhosis, a progressive condition for which there is no cure.29
Recent research reveals strong connections between the liver and other organs, reinforcing the need for a comprehensive approach that targets the root causes of liver and cardiometabolic diseases at every stage.30 MASH shares many of the same drivers as obesity, overweight, and T2D.13 Recent scientific discoveries have revealed strong genetic factors that can put certain individuals and populations at greater risk of MASH, adding a new dimension to our understanding of this complex condition.31
AstraZeneca is investing in cutting-edge science to tackle the metabolic, inflammatory, fibrotic and genetic drivers of MASH. Through precision medicine, we aim to develop targeted, personalised therapies that could halt disease progression and prevent cirrhosis or cancer. Our goal is to deliver next-generation therapeutics with unique benefits for people living with this disease of unmet urgent need.
[#early-innovations]
Early innovations and partnerships in metabolism
As part of our long-term commitment to developing innovative medicines for obesity, overweight, and cardio-renal-metabolic diseases, we work with partners who share our dedication to pioneering science and helping patients in need.
Eccogene: Small molecule treatment for obesity and overweight
Ionis: Precision medicine for MASH
Quell: Cell therapy for T1
[#ourpeople]
Our people
Built on an impressive legacy in cardiovascular, renal and metabolic (CVRM) research, we are strongly positioned to help build a healthier and longer future for people with these diseases. Our team of over 1,000 people spans more than 23 functions including early and late R&D, medical and commercial.
Our employees are accomplished and experienced scientists, researchers, clinicians, and healthcare and commercial professionals dedicated to advancing novel science and driving practice change to benefit patients with CVRM diseases.
References
1. Lazarus E, Ortiz-Pujols S. Increasing clinical awareness of obesity as a serious, chronic, relapsing, and treatable disease. Am J Manag Care. 2022;28(15 Suppl):S271-S8.
2. Chew NWS, et al. The global burden of metabolic disease: Data from 2000 to 2019. Cell Metab. 2023;35:414–28.
3. Asadi A, et al. Obesity and gut–microbiota–brain axis: A narrative review. J Clin Lab Anal. 2022;36:e24420.
4. World Health Organization. Obesity and overweight [Internet]. World Health Organization. 2025 [cited 2025 Sep 3]. Available from: https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight.
5. AstraZeneca. Data on file. 2024.
6. Fulton M, et al. Obesity, Stigma, and Discrimination [Internet]. StatPearls PubMed. Treasure Island (FL): StatPearls Publishing. 2023 [cited 2025 Sep 3]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK554571/.
7. Frank AP. Determinants of body fat distribution in humans may provide insight about obesity-related health risks. J Lipid Res. 2018;60:1710–9.
8. Bloor ED, Symonds ME. Sexual dimorphism in white and brown adipose tissue with obesity and inflammation. Hormones and Behavior. 2014;66:95–103.
9. Ning T, Wang QA. Adipose Tissue Remodeling and Adipose Precursors. Encyclopedia of Tissue Engineering and Regenerative Medicine. 457–62. Elsevier (NL). 2019.
10. Bansal S, et al. Visceral fat: A key mediator of NAFLD development and progression. Human Nutr Metab. 2023;33:200210.
11. Crewe C, et al. The ominous triad of adipose tissue dysfunction: inflammation, fibrosis, and impaired angiogenesis. J Clin Invest. 2017;127:74–82.
12. Tanaka H, et al. Cognition, Brain Structure, and Brain Function in Individuals with Obesity and Related Disorders. Curr Obes Rep. 2020;9:544–9.
13. Theodorakis N, Nikolaou M. From Cardiovascular-Kidney-Metabolic Syndrome to Cardiovascular-Renal-Hepatic-Metabolic Syndrome: Proposing an Expanded Framework. Biomolecules. 2025;15:213.
14. Ellulu MS, et al. Obesity and Inflammation: the linking mechanism and the complications. Arch Med Sci. 2017; 13,4:851–863
15. Diabetes and Health-Related Quality of Life [Internet]. Physiopedia [cited 2025 Sep 03]. Available from: https://www.physio-pedia.com/Diabetes_and_Health-Related_Quality_of_Life.
16. AstraZeneca. Diabetes: Following the science in the search for a cure [Internet]. Nature [cited 2025 Sep 03]. Available from: https://www.nature.com/articles/d42473-021-00264-7.
17. Ruze R, et al. Obesity and Type 2 diabetes mellitus: connections in epidemiology, pathogenesis, and treatments. Front End. 2023;14:1161521.
18. International Diabetes Federation. IDF Diabetes Atlas (11th ed.). 2025.
19. Diabetes UK. Weight management services for preventing and managing type 2 diabetes: Position statement [internet]. Diabetes UK. 2024 [cited 2025 Sep 10]. Available from: https://www.diabetes.org.uk/about-us/about-the-charity/our-strategy/position-statements/treatment-of-obesity.
20. Klein S, et al. Why does obesity cause diabetes? Cell Metab. 2022;34:11–20.
21. World Health Organization. The top 10 causes of death [Internet]. World Health Organization. 2024 [cited 2025 Sep 3]. Available from: https://www.who.int/news-room/fact-sheets/detail/the-top-10-causes-of-death.
22. World Health Organization. Diabetes [Internet]. World Health Organization. 2024 [cited 2025 Sep 3]. Available from: https://www.who.int/news-room/fact-sheets/detail/diabetes.
23. Patel MR. Financial Toxicity in Diabetes: The State of What We Know. Curr Diab Rep. 2025;25:32.
24. Rushforth B, et al. Barriers to effective management of type 2 diabetes in primary care: qualitative systems review. Br J Gen Pract. 2016;66(643):e114-27.
25. American Diabetes Association. Diabetes Care 2024;4(Suppl 1):S1–S321.
26. Williams DM, et al. Diabetes Metab Syndr Obes 2022;15:281–295.
27. National Institute of Diabetes and Digestive and Kidney Diseases. Definition & Facts of NAFLD & NASH [Internet]. National Institute of Diabetes and Digestive and Kidney Diseases. 2019 [cited 2025 Sep 3]. Available from: https://www.niddk.nih.gov/health-information/liver-disease/nafld-nash/definition-facts.
28. Wexler M. Global Fatty Liver Day to raise awareness of “concealed epidemic” [Internet]. Liver Disease News. 2024 [cited 2025 Sep 3]. Available from: https://liverdiseasenews.com/news/global-fatty-liver-day-raise-awareness-concealed-epidemic/.
29. European Association for the Study of the Liver, et al. EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. J Hepatol. 2016;64(6):1388-402.
30. National Institute of Diabetes and Digestive and Kidney Diseases. Treatment for Cirrhosis [Internet]. National Institute of Diabetes and Digestive and Kidney Diseases. 2019 [cited 2025 Sep 03]. Available from: https://www.niddk.nih.gov/health-information/liver-disease/cirrhosis/treatment.
31. Ye DW, et al. Liver-adipose tissue crosstalk: A key player in the pathogenesis of glucolipid metabolic disease. Chin J Integr Med. 2017;23(6):410-4.
32. Pei Y, Goh GBB. Genetic Risk Factors for Metabolic Dysfunction-Associated Steatotic Liver Disease. Gut Liver. 2025;19:8-18.
Veeva ID: Z4-76791
Date of preparation: September 2025