ORIGINALLY PUBLISHED
4 November 2025
Obesity is a known driver of complications and comorbidities across cardiometabolic and kidney health.1
The AstraZeneca-sponsored 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.2-6 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).2
The study used different BMI thresholds to define obesity in each country, reflecting local criteria and datasets: ≥30 kg/m² in the US and ≥25 kg/m² in Japan. 2
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.7,8
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, among 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.4
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.
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%).3
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.
The risk trajectory: complications develop over time and the sequence matters
Longitudinal analyses from the CALOR programme show that the risk of developing CKD and heart failure (HF) increased over time in people living with overweight or obesity. The risk of these complications is particularly amplified in people living with type 2 diabetes as well, who experienced an additional two- to three-fold higher risk of developing CKD and around a 1.5-fold increase in HF risk compared with people without type 2 diabetes.5
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.
Further trajectory data from over 2.8 million people in the US, UK and Japan provide insight into how CKD and HF develop following a diagnosis of type 2 diabetes, showing that risk not only increases over time, but can also compound once one complication has developed.6
In both the US and UK, within five years of a type 2 diabetes diagnosis, CKD was more than twice as likely as HF to be the first cardiorenal complication. In Japan, the pattern was reversed, with the risk of developing HF first (8.6%) being nearly twice as high as the risk of developing CKD first (4.4%).6
However, complications do not just accumulate; the order in which they appear can shape what comes next. Once patients developed either CKD or HF, they faced a considerable 5-year risk of subsequently developing the other complication, although the pattern differed across countries. These findings provide important insight into how cardiorenal disease progresses following a T2D diagnosis, an area where temporal evidence has been limited.6
Viewed over the longer term, the combined risk of developing CKD, HF or death at five or ten years after a type 2 diabetes diagnosis was considerable across countries.6
These findings show that complications do not just accumulate; they compound. Once someone develops CKD or HF, there is a substantial risk of subsequently developing the other. This reinforces the importance of not managing type 2 diabetes, CKD and HF as separate conditions, and highlights the need for earlier, more proactive and joined-up care.
CALOR: guiding the path forward
Many national approaches to patient care remain siloed, with obesity prevention and management often separated from strategies for managing interconnected CVRM conditions.7 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.
The CALOR findings reinforce a clear message: if obesity is diagnosed late, interconnected health comorbidities will have already advanced. Earlier intervention is likely to change this trajectory – enabling more timely intervention, co-ordinated care and improved long-term outcomes.2
By translating real-world insights into scientific and clinical innovation, AstraZeneca is helping to shift obesity care from reaction to prevention.
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
- Yang M, et al. The Related Metabolic Diseases and Treatments of Obesity. Healthcare. 2022;10(9):1616.
- 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
- Sattar N, et al. Cardiorenal disease trajectories in patients newly diagnosed with type 2 diabetes. Presented at European Association for the Study of Diabetes (EASD) Congress; 28 September – 2 October 2026; Milan, Italy
- 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: September 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.
- 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: September 2026)
Veeva ID: Z4-89080
Date of preparation: September 2026