The worldwide prevalence of obesity has more than tripled since 1975,1 yet no two people experience the disease in the same way. As we enter a new era of weight management, AstraZeneca is researching approaches built on diverse mechanisms and tailored solutions designed to improve long-term health for people living with obesity. Our approach goes beyond treatment as a standalone focus – it is about learning from people’s lived experiences, partnering with governments, health systems, patient advocates, healthcare professionals and providers, and following the science to help people live better, healthier lives.
Understanding obesity: A chronic, multifactorial disease
Today, nearly three billion people worldwide are living with obesity or overweight.1 With rates rapidly rising, effective and accessible management options are urgently needed to address individuals’ goals, reduce the escalating economic burden2 and limit the rising prevalence of associated chronic diseases.3,4
Obesity is recognised as a chronic, relapsing5 and multifactorial disease, driven by the complex interactions between biology, environment and society6 by leading health organisations, including the World Health Organization (WHO),7 American Diabetes Association (ADA),8 Centers for Disease Control and Prevention (CDC)9 and European Association for the Study of Obesity (EASO).10
Obesity affects people across every region, age group and socioeconomic background.7 However, different ethnicities and communities face varying risks, barriers and needs.11
Our CVRM-first approach: Looking beyond weight loss
Weight alone does not fully explain health status.12 People with the same body mass index (BMI) can have very different risks, biological root causes and treatment needs.12,13
Obesity is a disease and it needs to be recognised as that and have the respect that it deserves. Somebody who is morbidly obese needs help, they need support, and they need guidance, rather than being pushed aside
Over 60% of people living with obesity have at least one obesity-related comorbidity.14 In particular, among U.S adults aged over 65 with obesity, up to 85.9% are living with multiple comorbidities.15
Further, obesity contributes and exacerbates over 200 complications,16 including type 2 diabetes (T2D), cardiovascular disease, chronic kidney disease (CKD) and fatty liver disease,17 highlighting the need to focus on the underlying biology of this complex disease in addition to weight loss.
Understanding fat distribution is key to managing a person’s risk factors effectively, as the different distributions of fat in the body influences the development of comorbidities and complications.18 Visceral fat, which is fat found deep within the abdomen and surrounding organs, is highly active and drives much higher cardiometabolic and kidney risk than BMI may suggest. On the other hand, subcutaneous fat is found directly under the skin and is generally less harmful.19 Similarly, body composition, including muscle mass, fat percentage and distribution, are important measures that influence long-term health.20
BMI alone doesn’t always accurately reflect an individual’s risk to develop an obesity-related complication. Scientific evidence, including our analysis of data from UK Biobank – assessing over 300,000 adults living with obesity – demonstrates that individual metabolic profiles, including where fat is stored and how much muscle is preserved, significantly influences health outcomes.21
The unmet need: Why we need a new approach
Obesity is not always formally diagnosed, partly because obesity is often not recognised as a chronic disease.22 As a result, many people do not receive structured assessment or early support.23,24
Another barrier to diagnosis and early treatment of obesity is the fear of stigma. This can lead to the avoidance of seeking medical care, which may increase risk factors, and ultimately raise the likelihood of developing further weight-related diseases.25
Data from the AstraZeneca-funded CALOR study,26,27 and other real-world analyses show that many people remain undiagnosed. For those that receive a diagnosis, this is often delayed until after the development of a complication.26 This limits earlier intervention opportunities and shifts care towards symptom mitigation rather than prevention efforts.28
People without a formal diagnosis of obesity or overweight can still experience substantial cardiometabolic burden, underlining the need for consistent diagnostic pathways.27
Across this landscape, three key unmet needs stand out to us at AstraZeneca:
- Underdiagnosis and under-recognition can lead to a lack of action27
- Variation in individual tolerability and response to treatment13
- The need for solutions that support sustainable, long-term weight management29
Our vision: Pioneering Next-Generation Therapeutics
Obesity is not a single disease, so no single mechanism will work for everyone. Moreover, different biological pathways drive cardiometabolic risk in different people, which is why a range of complementary mechanisms is essential to deliver meaningful, durable cardiometabolic benefit
Tailored options
Obesity is a biologically complex disease, not driven by a single pathway. Therefore our approach to obesity needs to be multi-faceted, considering comorbidities, appetite regulation, fat storage, metabolic rate, hormonal signalling, inflammation and muscle preservation.30 Given tolerability and response to existing therapies varies widely,13 our focus is on next-generation approaches that can be tailored to individual patient needs and preferences, while addressing the biological root causes of obesity.
Obesity doesn’t exist in isolation and neither should its care. At AstraZeneca, we are focussed on advancing a tailored approach for obesity management – one that moves beyond single-pathway solutions to address the complexity of the disease and its full body impact. Our aim is to help people receive treatment and management that reflects their unique biology, health profile and long-term needs.
Sustainable weight management
A major unmet need and key priority for AstraZeneca is the focus on sustainable, long-term weight management versus short-term weight loss.
Sustainable weight management means helping people reach and maintain improved health, not simply achieving a number on the scale.
This perspective aligns with a broader focus on healthcare resilience, where enduring improvements in cardiometabolic, kidney, liver and muscle health contribute to stronger individuals and systems.
AstraZeneca is working to advance next-generation innovation in obesity and weight management to move beyond short-term weight loss and deliver sustainable, long-term health solutions. Our ambition is to address the needs of people living with obesity – helping them live healthier lives through transformative science that lasts.
Our science: A long-standing commitment to research
At AstraZeneca we are investing in deep and rigorous science to better understand the complex biology of obesity and its impact across the whole body. This commitment is helping to advance knowledge that can support more informed, long-term approaches to care.
Our focus on functional health and wellbeing aims to strengthen the resilience of healthcare systems and give people everywhere the chance to be as healthy as possible.
Obesity is a progressive disease and a root driver of many chronic conditions including type 2 diabetes, ASCVD, heart failure, MASH, and chronic kidney disease. Clinical management need to focus on treating obesity with the dual goals of reducing weight, as well as preventing irreversible organ damage. Building on our CVRM heritage, AstraZeneca is developing a weight management portfolio designed to deliver strong efficacy, good tolerability, organ protection and meaningful reductions in obesity-related disease.
The pathways we’re investigating
GLP-1
GLP-1 receptors are found in the brain and pancreas. GLP-1 agonists mimic the natural GLP-1 hormone, helping lower blood sugar and reduce body weight by increasing feelings of fullness and slowing digestion.31
Amylin
Amylin, a hormone secreted by the pancreas, enhances satiety via a different receptor system than GLP-1 – offering a complementary way to help people feel full and reduce food intake.32 It slows stomach emptying and suppresses post-meal glucagon secretion from the liver, supporting glucose control.32
Emerging evidence suggests amylin-based approaches may help retain or preserve muscle,33 adding an important dimension for healthy, sustainable weight loss.
Glucagon
In a pre-clinical model, it has been seen that glucagon-based mechanisms can potentially increase energy expenditure by promoting fat breakdown in the liver.34
It has also been observed that these mechanisms mobilise fat stores and potentially influence how the liver handles lipids, supporting reductions in excess fat while maintaining metabolic balance.34
Activin
Activin pathways are involved in regulating muscle mass and body composition, including fat metabolism.35,36 Blocking these pathways may help to preserve muscle mass, which is key for sustainable, healthy weight loss, helping people maintain strength, function and metabolic health as weight comes down.37
These pathways may also affect inflammation, metabolic health and long-term function, and therefore support maintaining muscle health and improving fat-specific loss.31,37, 38
This underlines a shift toward medications that focus on maintaining a healthy body composition and physical function, rather than weight reduction alone.
Why multiple pathways matter together
No single mechanism addresses the full biological complexity of obesity. Obesity is multifactorial, resulting from genetic, molecular, environmental, and behavioural interactions.6 At AstraZeneca, we are researching ways to combine different therapies to offer medicines that can potentially target different mechanisms.
In particular, we are exploring how different oral medications can be used together to potentially help patients manage excess weight, its health complications and other associated diseases.
Our growing R&D pipeline aims to target the underlying causes and mechanisms of obesity and aims to provide purpose-built combinations that can harmonise CVRM care, address health outcomes and quality of life as well as offer treatment strategies tailored to the individual needs and preferences of people living with obesity.
Our commitment to patients & communities
AstraZeneca’s approach to obesity goes beyond developing medicines. It is about respecting people’s lived experiences, strengthening trust in care and designing science that reflects the real world to support people living with obesity and other weight-related conditions.
This commitment shapes how we communicate, how we run our studies and how we ensure innovations reach the people who need them most.
Nicci’s powerful story brings this commitment to life, sharing one family’s lived experience of obesity and the transformative impact of compassionate, evidence-based care.
Tackling stigma with the right approach
Experiences of weight stigma in healthcare settings can lead individuals to avoid seeking medical care, delay preventive services, and reduce trust in healthcare providers
Language shapes care. Real-world evidence shows that people living with obesity often encounter judgmental or dismissive language that discourages them from seeking support.39
Plainspoken, empathetic communication fosters trust and improves engagement.39
This includes clear and consistent terminology, using a more sensitive and respectful approach with the use of neutral terminology, which could reinforce obesity as a chronic disease rather than a personal failing.39
By putting lived experience at the centre of our principles and commitments, we recognise the importance of people living with obesity being listened to and understood.
Designing inclusive clinical trials
Representing the world we serve is a core priority. At AstraZeneca, we intentionally design clinical research to reflect the diversity seen in real clinical practice, including a range of locations, ages, BMI categories, comorbidities, as well as ethnic and racial backgrounds.
Evidence from the CALOR study shows that many people with obesity carry substantial cardiometabolic burden even before receiving a diagnosis of obesity, underscoring the need for research populations that reflect this complexity.26 Furthermore, insights from analysis of UK Biobank data reinforce that risk can vary between people with similar BMI.21
So, AstraZeneca prioritises endpoints that reflect full body health, and our study designs incorporate insights about the lived experience of patients to ensure endpoints, study participation, and patient materials reflect patients’ key priorities.
Hear from Professor Melanie Davies, lead of a centre of research excellence, as she shares her priorities in obesity and weight management research.
Innovation in obesity management only matters if it reaches the people who need it most. By listening to and learning from the community – better understanding their experiences, challenges and goals – we can develop treatments that are not only scientifically advanced, but meaningful to their everyday lives.
Collaborations and partnerships in obesity and weight management
As part of our long-term commitment to developing innovative medicines for obesity, we work with partners who share our dedication to pioneering science and helping patients in need.
Eccogene
Collaboration centred on developing potential oral treatment of obesity and type 2 diabetes
SOPHIA Consortium
Delivering evidence-based insights to redefine obesity and optimise future treatment
CSPC Pharmaceuticals
Advancing the development of multiple next-generation therapies for obesity and type 2 diabetes
The Foundation for the National Institutes of Health (FNIH) Biomarkers Consortium
Comparing technologies for body fat distribution measurements
Shanghai Institute of Materia Medica, Chinese Academy of Sciences (SIMM)
Early research collaboration exploring unimolecular and combination small molecules for obesity
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Veeva ID: Z4-80019
Date of preparation: May 2026