Review Article

Managing Obesity in Individuals with Cardiovascular Disease: Are We Missing the Obvious?

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Abstract

Obesity is a modifiable driver of cardiovascular disease and coexistent diabetes adds to adverse vascular outcomes. Guidelines uniformly highlight weight management as a cornerstone of cardiovascular prevention and recommend stepwise strategies starting with lifestyle modifications, then pharmacotherapies, followed by bariatric surgery in non‑responders. Despite a large body of evidence, use of weight loss cardiovascular protective agents remains low in clinical practice due to high costs and limited familiarity. Additional barriers include inadequate prioritisation of weight management in cardiac care, fragmented cross-specialties coordination, and lack of specific guidance in some high‑risk groups (e.g. those with type 1 diabetes). Given various difficulties, implementation of effective anti-obesity strategies remains suboptimal and requires more support of non-specialists together with greater efforts to align healthcare provider practices and system-level policies to ensure the delivery of equitable and sustainable weight loss interventions at scale.

Keywords

Cardiovascular disease, diabetes, obesity, overweight, weight management,

Received:

Accepted:

Published online:

DOI: https://doi.org/10.15420/ecr.2025.53

Disclosure: RAA has received institutional research grants from Abbott Diabetes Care, Bayer, Eli Lilly and Novo Nordisk and honoraria/education support/consulting fees from Abbott Diabetes Care, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Dexcom, Eli Lilly, GlaxoSmithKline, Menarini Pharmaceuticals, Merck Sharp & Dohme and Novo Nordisk. All other authors have no conflicts of interest to declare.

Correspondence: Ramzi A Ajjan, Leeds Institute for Cardiovascular and Metabolic Medicine, University of Leeds, Woodhouse Lane, Leeds LS2 9JT, UK. E: R.Ajjan@leeds.ac.uk

Copyright:

© The Author(s). This work is open access and is licensed under CC-BY-NC 4.0. Users may copy, redistribute and make derivative works for non-commercial purposes, provided the original work is cited correctly.

Cardiovascular disease (CVD) remains the leading cause of premature mortality globally.1 Among the modifiable risk factors for CVD is obesity, a global epidemic that affects billions, with prevalence having more than doubled since the 1980s.2 Obesity has been shown to rapidly accelerate CVD through established mechanisms, including chronic inflammation, insulin resistance and endothelial dysfunction.3 These pathophysiological processes amplify established CVD risk factors, including type 2 diabetes (T2D) and dyslipidaemia.4

Despite substantial advancements in both interventional and pharmacological treatment, outcomes in individuals with obesity (particularly central obesity) remain disproportionately poor.5 This may be related to the relatively limited attention to obesity in cardiology care pathways, largely due to historical absence of effective treatments.6 This has contributed to both under-recognition and under-treatment of obesity in cardiovascular practice. This represents a gap in cardiovascular care, where a well-recognised modifiable risk factor remains insufficiently addressed.

The European Society of Cardiology noted that 67.5% of obesity-related mortality is due to CVD and identified glucagon-like peptide-1 receptor agonists (GLP-1RAs) as key drugs with proven outcomes in this population.7 In individuals with diabetes, a group with increased CV risk, early introduction of cardioprotective agents, including GLP-1RAs and sodium–glucose cotransporter 2 inhibitors (SGLT2Is) are advocated, particularly in the presence of obesity.8 In contrast to T2D, clear guidance on managing obesity in type 1 diabetes (T1D) is lacking, despite the increased CVD risk in overweight individuals with T1D.9

To complicate matters, some studies have documented an “obesity paradox”, whereby individuals classified as overweight or having class 1 obesity appear to have better short- and mid-term cardiovascular outcomes than their low or normal BMI counterparts.10 However, many studies supporting the obesity paradox overlook individuals with central obesity, in whom excess visceral fat contributes to worse long-term outcomes.11 This is a key limitation of using BMI as an obesity measure, which can fail to reflect true metabolic risk and fat distribution.12 Moreover, a recent meta-analysis has questioned the validity of the paradox, suggesting that these findings may be influenced by selection bias, collider stratification bias, and reverse causality.13

The aim of this paper is to provide of overview on managing obesity to reduce cardiovascular risk, with a focus on coronary artery disease (CAD), spanning groups with normoglycaemia to those with deranged glucose metabolism, including T1D and T2D. Details of the literature search can be found in the Supplementary Material.

Obesity, CVD and Normoglycaemia

Obesity is well-established as a significant risk factor for CVD through multiple interrelated mechanisms.3 Excess adiposity contributes to CAD and heart failure (HF) through association with traditional risk factors (hypertension, hyperglycaemia, dyslipidaemia, insulin resistance) and promotion of an inflammatory environment.3 Individuals with obesity, especially those with excess abdominal/visceral fat, tend to develop complex atherosclerotic plaques at younger ages and have higher cardiovascular mortality than normal-weight individuals.14,15

Epidemiologic studies indicate that each standard deviation increase in BMI raises the risk of coronary events by about 20%.16 Even in metabolically healthy individuals with obesity, there is a higher HF risk (HR 1.65; 95% CI [1.30–2.09]) compared to healthy-weight adults in nearly 30 years of follow-up.17 Clinically, individuals with HF and obesity often have worse cardiac function compared to individuals with healthy weight.18

These findings explain why major clinical cardiovascular guidelines advocate weight management as a critical component of cardiovascular care, and highlight multidisciplinary approaches, including nutrition, exercise and behavioural support.3,7,19–22 However, implementing weight-loss strategies has been challenging due to the effort required by individuals with CVD and healthcare professionals, as well as the general absence of effective weight loss medications until relatively recently.

Lifestyle modification remains the first-line strategy for weight management in individuals with CVD and obesity.7,23,24 As weight loss through lifestyle changes alone has not consistently reduced CAD event rates, recent guidelines and consensus statements also acknowledge newer therapies such as GLP-1RAs, originally developed to manage hyperglycaemia in individuals with T2D, and which have repeatedly shown cardiovascular benefits.25–27 When neither lifestyle nor therapeutic agents are effective at managing obesity, bariatric/metabolic surgery is considered, particularly in cases of severe obesity and the presence of comorbidities.7,28,29

Lifestyle therapy usually achieves modest weight loss, associated with clinically relevant improvements in functional and vascular risk factors, but gains typically peak by 6 months and attenuate by 12, making the long-term benefits questionable. Bariatric/metabolic surgery reduced the largest and most durable weight with significant cardiometabolic gains (Supplementary Table 1). However, surgical approaches are constrained by access and require lifelong postoperative monitoring, with procedure-specific adverse effects.30 In contrast, GLP-1RAs therapies, both injectable and oral, provide substantial weight loss and have shown to improve cardiovascular risk, offering a scalable adjunct to guideline-directed cardiometabolic care.

While obesity management is mentioned in CVD guidelines, this is not regularly implemented. A European multi-country study (EUROASPIRE) of more than 10,000 individuals with CAD found that less than 20% had healthy BMI at the time of their cardiac hospitalisation, with 35% being obese and 46% overweight.31–33 Worryingly, over one-third of individuals with CVD and obesity in the survey received no advice on dietary or physical activity, and nearly one-quarter were not even told they were overweight. The failure to focus on obesity management in individuals with CVD contributes to worse outcomes in this population.32 These findings suggest that obesity is not usually regarded by healthcare professionals as a serious medical problem requiring intervention in real-world settings. Alternatively, the failure to tackle obesity may be related to limited familiarity with current anti-obesity agents or simply due to cost implications

In addition to outcome studies, cost-effectiveness analysis is required to justify prescription of anti-obesity agents. Also, given the obesity epidemic, future studies should adopt a pragmatic approach starting with the lowest cost intervention, escalating treatment according to preset targets that are known to influence CV risk. Indeed, beneficial weight loss has been defined in the 2025 ACC expert consensus statement, but it remains unclear whether the relationship between the degree of weight loss and CVD benefit is linear or if there is a more complex interaction necessitating individualised targets for each individual.30 Moreover, the CV benefits of some agents may be independent of weight loss, calling for the identification of easy-to-measure markers than can track the vascular benefits of a particular weight loss management strategy.

Overall, integrating structured weight management into standard cardiac care holds great promise but will require more evidence of the best modality to use and the degree of beneficial weight loss in each individual while also conducting health economic analyses.

Obesity, CVD and Hyperglycaemia

Type 2 Diabetes

Obesity is often accompanied by hyperglycaemia, which further increases the risk of cardiovascular events and mortality by twofold to fourfold.8,34 In addition, T2D and obesity are independent risk factors for chronic kidney disease, a condition that independently increases the risk of cardiovascular events.35 Even pre-diabetes and metabolic syndrome are linked to an almost 15% increased risk of CAD and a similar increase in stroke risk compared to normoglycaemia.36 The combination of obesity and T2D creates the perfect storm of metabolic and inflammatory derangements that accelerate atherosclerosis, worsen coronary plaque instability, and impair cardiac function, explaining the disproportionately higher rates of cardiovascular events, HF, and mortality in this group.

A UK Biobank cohort study reported that T2D independently raises cardiovascular mortality by 55% compared with metabolically healthy, normal-weight adults. Adding excess body weight compounds this risk in a graded fashion with overweight pushing the excess risk to 70%, while obesity almost doubles the risk (HR 1.96).34 Moreover, obesity amplifies the adverse cardiovascular effects of other metabolic comorbidities and, therefore, we can no longer manage these conditions in isolation.

Given the presence of diabetes accelerates the “cardio-metabolic continuum” and the close relationship between obesity and diabetes, weight loss therapies received greater attention in this group compared to overweight individuals with normal glucose metabolism. Fortunately, international clinical guidance has prioritised optimising weight loss therapy in this population, given both the metabolic and cardiovascular benefits.8,22,25,37,38

Sustained adherence to lifestyle therapy is recommended, yet it seldom achieves durable weight loss sufficient to resolve complications in individuals with CVD and T2D (Supplementary Table 2). By contrast, bariatric surgery is highly effective but can have undesirable long-term consequences, whereas pharmacotherapy offers a more favourable benefit–risk ratio.39 GLP-1RAs can exert a beneficial cardiovascular effect not only through reducing weight but also through other mechanisms that are not necessarily related to weight loss.5 GLP-1RAs appear to reduce systemic inflammation and postprandial lipaemia, improve endothelial function and arterial stiffness, and modestly lower blood pressure.40 In SELECT, cardiovascular risk reduction with semaglutide occurred in individuals without diabetes and was independent of baseline or change in HbA1c, consistent with pleiotropic, weight- and glycaemia-independent mechanisms.26,41 Recent mechanistic and clinical studies further support decreases in high-sensitivity C-reactive protein and pro-atherogenic lipid species, enhanced microvascular perfusion, and attenuation of postprandial triglyceride excursions.42,43 It should be noted that newer dual GLP-1/glucose-dependent insulinotropic polypeptide receptor agonists are even more effective than GLP-1RAs at reducing weight in individuals with obesity with or without T2D with favourable cardiovascular outcomes (Supplementary Tables 1 and 2).44–46 In addition to this, there are new agents in the pipeline, such as once-monthly maridebart cafraglutide (MariTide) that may result in a more durable weight loss; data are awaited with interest.47 Recently, a small molecule mimetic of GLP-1 receptor, orforglipron, has shown promise as a weight loss agent that improves glycaemia in early T2D.48 Moreover, orforglipron treatment appears to improve vascular biomarkers and cardiovascular outcome studies are awaited with interest.49

Other agents that induce weight loss are the SGLT2I family of drugs that have shown cardiovascular protective properties, mainly related to improvement in HF.50 These agents are less effective at reducing weight and, unlike GLP-1RAs, do not appear to significantly affect the atherosclerotic process as their effects are mainly haemodynamic, explaining their benefits in various forms of HF. However, weight loss is modest at best with SGLT2Is and not a central factor in their beneficial cardiac effect; therefore, unlike GLP-1RAs, they are not regarded as anti-obesity medications.

Despite clear evidence and consensus recommendations, real-world implementation of guideline-directed therapies remains inadequate. Usage of GLP-1RAs among eligible individuals with T2D and cardiovascular comorbidity remains low despite the strong clinical data.5 In the US, it has been estimated that approximately 1–5% of people with diabetes are prescribed GLP-1RAs.51 Europe does not fare much better as a database study in Spain, recently showed <5% individuals with T2D on this treatment, while in the UK, GLP-1RAs account for 5% of the total items prescribed for diabetes in 2024/2025.52,53 Key studies summarising the benefits of these agents on weight and cardiovascular risk in T2D are summarised in Supplementary Table 2.

Several factors may contribute to this deficient implementation; therapeutic inertia, limited familiarity with novel pharmacological agents, and uncertainty regarding long-term safety profiles may hinder prescribing behaviours among clinicians.54 Additionally, financial barriers remain substantial; high costs and formulary restrictions were identified as major barriers to GLP-1RA usage in practice limiting their accessibility in both high- and low-income settings.

Another factor may be fragmented clinical care as individuals with obesity, T2D and CVD often see multiple specialists. Lack of coordination may lead to disjointed and inconsistent management. For example, cardiologists may prioritise cardiac outcomes while overlooking metabolic and weight-related issues, whereas endocrinologists may focus entirely on metabolic factors. Without coordinated care pathways and clearly defined roles, crucial aspects of treatment may be neglected.

Individual-level barriers also deserve attention. Adherence to complex treatment regimens involving multiple medications and lifestyle modifications can be challenging. Additionally, weight stigma within healthcare environments may discourage individuals from seeking timely and appropriate care.

Type 1 Diabetes

Throughout history, T1D has often been regarded as a condition primarily affecting individuals with a normal or low BMI.55 In recent decades, however, the prevalence of overweight and obesity among those with T1D has increased significantly.9 This could be attributed to several factors, including the general global obesogenic trend, but also an intensified insulin regimen and insulin delivery method (subcutaneous rather than portal venous), which can induce peripheral insulin resistance.9 Such treatment promotes weight gain and fat accumulation through a complex interplay of insulin-driven physiological mechanisms and behavioural responses aimed at preventing hypoglycaemia.56 Despite the growing prevalence of the obesity–CVD–T1D triad, there remains a striking lack of guideline recommendations for managing obesity while maintaining optimal glycaemic control in T1D, despite its clear CVD implications.

CVD is widely recognised as the leading cause of morbidity and mortality in individuals with T1D.1 These individuals face a markedly higher risk of cardiovascular complications, including HF and CAD, with events occurring 10–15 years earlier and at a fourfold to 10-fold greater rate than in individuals without diabetes.57 This is further supported by a landmark study by Rawshani et al., which reported that individuals diagnosed with T1D before the age of 10 had a 30-fold increased risk of CAD and an average loss of 14.2 years of life expectancy compared to matched controls with normal glucose metabolism.58

While several guidelines, such as the European Society of Cardiology, American Diabetes Association and National Institute for Health and Care Excellence, acknowledge the increased CVD risk in individuals with T1D who are overweight or have obesity, there is a clear absence of tailored recommendations for obesity management in this group.8,20,59 In contrast, individuals with T2D benefit from both pharmacological and structured weight management pathways, which are absent in T1D guidelines, even for those with coexisting CVD. Agents of the GLP-1RA family have shown promise in individuals with T1D, particularly those who are overweight or have obesity. Notably, two Phase III trials, ADJUNCT ONE and ADJUNCT TWO, assessed liraglutide in over 2,200 individuals with T1D.60,61 Results demonstrated a dose-dependent weight loss of up to 5.1 kg, and improvements in quality-of-life scores, but the relatively small drop in HbA1c of 0.33% limited enthusiasm for this treatment. A key difficulty in T1D is the absence of outcome studies with GLP-1RAs, given the attention is devoted to individuals with T2D.

Other agents with weight-loss properties have been investigated in T1D such as SGLT2I in the DEPICT-1 and DEPICT-2 trials, which included over 1,600 individuals with T1D.62,63 Over 52 weeks, dapagliflozin 5 and 10 mg significantly reduced HbA1c (up to 0.36%) and body weight (up to 4.9%) compared to placebo but were associated with a higher incidence of diabetic ketoacidosis (up to 4%), though most events were mild. Beyond clinical trials, real-world data support these findings; a 5-year cohort study (n=1,822 on GLP-1RA and n=992 on SGLT2I) showed higher reduction of HbA1c with GLP1-RA versus SGLT2I (5.4 versus 2.6 mmol/mol, respectively) but better protection of renal function and lower HF with the latter treatment. However, the observational nature of this work makes it difficult to draw definitive conclusions of the superiority of one agent over the other.64 A comprehensive review of adjunctive therapies in T1D has been recently published, which emphasises the lack of adequately powered hard endpoint outcome trials in this population.65

Despite promising evidence of SGLT2I and GLP-1RA in T1D, continued exclusion of this group from CVD trials remains a concern, limiting our understanding of how best to target obesity alongside glycaemic control to reduce CVD risk in T1D. In individuals with T1D, obesity is associated with abnormal lipid profile and increased insulin resistance, hypertension and subclinical atherosclerosis, all of which further exacerbate the already elevated cardiometabolic risk.66 While several studies have demonstrated that GLP-1RA use can reduce body weight and insulin dose requirements in this population, the absence of vascular outcome studies has limited the use of these agents in T1D.67 It can be argued, however, that these agents are beneficial in both T2D and normoglycaemia and, therefore, why should the T1D population be different?

Key studies summarising the benefits of lifestyle and pharmacological agents on weight and cardiovascular risk are presented in Supplementary Table 3.

Conclusion

There is little doubt that obesity increases cardiovascular risk in general, with hyperglycaemia acting as a force multiplier. As the evidence mounts, the message is increasingly consistent; obesity is an important part in CVD management in individuals with or without hyperglycaemia. Although global clinical guidelines advocate for weight management as a core component of care in CVD, the guidance lacks clear targets, akin to those seen with other cardiovascular risk factors. To further complicate matters, implementation of weight-loss strategies in practice is suboptimal. In particular, the use of cardiovascular protective agents that promote weight loss, including GLP-1RAs and dual GLP-1/glucose-dependent insulinotropic polypeptide agonists, remains alarmingly inadequate even in high-income countries. While cost implications play a role in the reduced prescription of cardiovascular protective agents, there is also the fundamental issue of limited familiarity with these agents and/or the focus on other risk factors. Moreover, some groups, such as those with T1D, particularly lose out due to lack of clinical recommendations secondary to the absence of adequately powered studies.

Figure 1: Summary of Barriers and Potential Actionable Integrated Care Pathways in Individuals at High Risk of Cardiovascular Disease

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Given the irrefutable evidence, GLP-1RAs should be used more frequently in individuals with CVD and obesity, whether they are normoglycaemic or have T2D. There is also a case for using these agents in T1D, but this is hindered by the lack of adequately powered outcome studies. A more prominent role for these agents in clinical cardiovascular guidelines would help expand their use, particularly in the presence of favourable cost-effectiveness analysis. Moreover, educating healthcare professionals on the benefits of these agents would also help increase their uptake. Addressing the interconnected challenges of obesity, diabetes and CVD can be a starting point as there should be little resistance to the use of GLP-1RA in such a population. This will require an effective working partnership between healthcare professionals in diabetes and cardiac health, which can take place through dedicated multidisciplinary cardiometabolic clinics optimising the care of high-risk individuals with the triad of obesity, diabetes and CVD. Although the implementation of such an approach remains challenging in routine clinical practice, delivering integrated obesity management programmes will improve cardiovascular health.

Figure 1 provides a summary of gaps in knowledge and barriers to targeting adequate weight-loss strategies and potential actionable integrated care pathways in individuals at high risk of CVD.

Click here to view Supplementary Material.

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