ORIGINALLY PUBLISHED
4 November 2025
Despite growing consensus that obesity is a chronic, relapsing, multifactorial disease, millions of people remain undiagnosed until serious health complications emerge.1,2,3
Findings from the AstraZeneca-sponsored CALOR real-world evidence study highlight a consistent pattern: obesity is often under-recognised, many people are already living with interconnected conditions by the time of diagnosis, and the risk of cardiometabolic and kidney disease continues to increase over time.4,5,6,7
Obesity is more than a number on the scale
Obesity is a known driver of complications and comorbdities across cardiometabolic and kidney health.8
The CALOR real-world evidence programme brings scale to this understanding, analysing data from millions of people living with obesity or overweight across the United States, United Kingdom and Japan.4,5,6,7 Through large, real-world datasets spanning multiple healthcare systems, CALOR provides a unique view of how obesity and its related conditions are experienced in routine clinical practice.
The hidden majority: underdiagnosis and its impact
Data from the CALOR programme highlight a persistent gap in recognition. Of the ~3.6 million people in the US studied, around 30% of those who met the clinical criteria for obesity (body mass index (BMI) ≥30 kg/m²) did not have a recorded diagnosis, despite established clinical pathways and the availability of effective treatments.4 In Japan, where formal recognition of obesity has historically been limited, only 2.3% of the ~3.1 million people included in the study had a recorded obesity diagnosis (BMI ≥25 kg/m²).4
This gap matters. Without a formal diagnosis, obesity may remain unmanaged – limiting access to guideline-based care, referrals, and co-ordinated support, and delaying opportunities for earlier intervention and prevention.3,9
As someone who has lived with obesity for most of my adult life, I know the reality of having your health reduced to ‘just try harder’. Too many people are still only recognised when serious complications have already developed, missing critical opportunities for earlier support, intervention and compassionate care. Obesity is not a simple issue of willpower or weight alone; it is a complex, chronic disease that impacts multiple aspects of health, and these findings highlight why earlier recognition and more holistic, person-centred care are urgently needed.
The weight of comorbidity: diagnosed late, complicated early
For many people, obesity is identified once obesity-related conditions have already developed. As seen in the CALOR analyses, the prevalence of type 2 diabetes and interconnected cardiometabolic and kidney diseases, such as hypertension, dyslipidaemia, chronic kidney disease (CKD) and heart failure (HF), is substantial in people with recorded overweight or obesity in the United States and Japan.4
In the US, 87% of people with obesity or overweight had at least one cardiorenal comorbidity, rising to 99% among those with type 2 diabetes. In Japan, comorbidity prevalence was also high—64% of people with obesity or overweight had at least one cardiorenal comorbidity— which was even higher among those with type 2 diabetes (prevalence increased to 82%).5
These findings suggest that many individuals are already living with multiple, interconnected conditions by the time obesity is diagnosed – reinforcing the need for earlier, more holistic approaches to care.
The data show that when obesity and type 2 diabetes coexist, the risk of cardiovascular and renal complications rises sharply. This underscores the need to move beyond treating these conditions in isolation and to recognise their shared biological and clinical pathways.
Furthermore, the analysis showed that among people with a recorded obesity diagnosis, occurrence of complications and comorbidities was higher compared to those without a diagnosis across both the US and Japan—underscoring how most individuals were already managing multiple conditions by the time obesity was formally recognised.4
Obesity and type 2 diabetes are deeply interconnected, driving overlapping cardiovascular, renal and metabolic risks. As their prevalence continues to rise, healthcare systems must evolve from fragmented, single-disease management to integrated, multi-specialty models that address shared risks earlier in collaboration with primary care. Real-world evidence from studies like CALOR strengthens the case for this shift — showing the broader impact of delayed recognition and why cardio-renal-metabolic protection must guide policy, guidelines and care delivery.
The risk trajectory: complications develop over time
Building on the high baseline burden of complications and comorbidities, longitudinal analyses from the CALOR programme show that the impact of obesity is not static – risk continues to increase over time.
Drawing on real-world data from more than 10 million people across the US and Japan, these findings show that the risk of developing CKD and HF increased substantially over time.7
Over time, the risk of developing CKD and HF increased - rising two- to three-fold within the first three years and up to five-fold over five years. This trajectory was further exacerbated in people living with type 2 diabetes, who experienced an additional two- to three-fold higher risk of developing CKD and around a 1.5-fold increase in HF risk. 7
These findings reinforce that the risk associated with obesity is not static. Without earlier recognition and intervention, the likelihood of developing serious complications continues to rise over time.
Understanding obesity through a new clinical lens
Together, these findings highlight that obesity is not only associated with a high and increasing burden of complications and comorbidities, but that these conditions are often interconnected. Analyses from the CALOR programme build on this by characterising how these complications and comorbidities cluster in real-world clinical practice using the European Association for the Study of Obesity (EASO) framework.
Across more than 7 million people living with obesity in the United States, United Kingdom and Japan, the majority were already living with obesity-related comorbidities driven by metabolic dysfunction, mechanical burden, or both.6
In the UK and Japan, over 50% of individuals had at least one of these disease drivers, while in the United States this rose to more than 80%. Notably, a substantial proportion, particularly in the US (43%), were living with both, highlighting the extent of overlapping, multi-system disease.6
What these data show is that obesity rarely exists in isolation. Many people are already living with multiple, overlapping comorbidities - highlighting the need to move beyond single-disease approaches to more holistic care.
Metabolic adipose disease is linked to disruptions in the body’s internal systems - such as metabolism and inflammation – for example type 2 diabetes or metabolic dysfunction-associated steatotic liver disease (MASLD). Mechanical adipose disease relates to the physical effects of excess weight on the body – for example osteoarthritis or obstructive sleep apnoea.
Using the EASO framework, CALOR data show that obesity is frequently associated with multiple, coexisting disease pathways. While the prevalence of these conditions varies across countries and healthcare systems, the presence of overlapping disease drivers highlights the complexity of obesity in real-world clinical practice and supports the need for more comprehensive, integrated approaches to management.
CALOR: guiding the path forward
The CALOR programme represents a cornerstone of AstraZeneca’s commitment to advancing understanding of obesity through a growing body of real-world evidence. By analysing millions of patient records across diverse healthcare systems, CALOR provides new insight into diagnostic trends, comorbidity burden, and the complex interplay between obesity, diabetes and other CVRM diseases.
Many national approaches to patient care remain siloed, with obesity prevention and management often separated from strategies for managing interconnected CVRM conditions.9 The insights from CALOR reinforce the need to develop more integrated, person-centred approach to care – supporting earlier identification, better co-ordination across specialties, and more holistic management of obesity and its comorbidities.
Ultimately, the findings underscore the importance of moving beyond a singular focus on weight to a broader, more continuous approach to CVRM health, one that reflects the interconnected nature of obesity and its associated conditions.
The CALOR findings reinforce a clear message: if obesity is diagnosed late, interconnected health comorbidities will have already advanced. Earlier intervention can help change this trajectory – enabling more timely intervention, co-ordinated care and improved long-term outcomes.4
Real-world insights are not just data points—they’re the stories of people who could have been identified sooner. If we act on this knowledge, we can change the trajectory of obesity.
Our ambition is clear: to lead a new era of obesity care and weight management, with integrated solutions and sustainable progress across the CVRM spectrum.
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References
- Kapoor A, et al. Weighing the odds: Assessing underdiagnosis of adult obesity via electronic medical record problem list omissions. Digital Health. 2020 Jan;6:205520762091871.
- World Health Organization. Obesity and Overweight. Available from: https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight. Last updated: 8 December 2025 (Accessed May 2026).
- Meron MK, et al. Missed diagnosis—a major barrier to patient access to obesity healthcare in the primary care setting. Int J Obes (Lond). 2024;48(7):1003–1010.
- Horn DB et al. Trends in Diagnosing Obesity (the CALOR study). Presented at ObesityWeek 2025; 04–07 November 2025, Atlanta, USA.
- Waki H, et al. Type 2 diabetes associates with higher occurrence of cardiorenal comorbidities in people living with overweight or obesity (the CALOR study). Presented at European Association for the Study of Diabetes (EASD) Congress; 15–19 September 2025, Vienna, Austria.
- McGowan, B et al. Characterising patients in routine clinical practice to support the EASO algorithm (CALOR study). Presented at ECO 2026; 12-15 May 2026, Istanbul, Turkey
- Horn DB, et al. Risk of developing cardiorenal complications in people living with overweight or obesity, with versus without T2D (CALOR study). Presented at ADA 2026; 05-08 June 2026, New Orleans USA
- Yang M, et al. The Related Metabolic Diseases and Treatments of Obesity. Healthcare [Internet]. 2022 Sep 1;10(9):1616. Available from: https://www.mdpi.com/2227-9032/10/9/1616 (Accessed: May 2026)
- Daley SF, et al. Overcoming Stigma and Bias in Obesity Management [Internet]. PubMed. Treasure Island (FL): StatPearls Publishing; 2025. Available from: https://www.ncbi.nlm.nih.gov/books/NBK578197 (Accessed: May 2026)
Veeva ID: Z4-83927
Date of preparation: June 2026