Overview

      Obesity is increasingly recognised not merely as excess weight, but as a chronic, relapsing, multisystem disease driven by dysfunctional adiposity. The Adiposity-Based Chronic Disease (ABCD) framework reframes obesity beyond BMI, integrating adipose tissue function, environmental and sociocultural context, and the burden of related complications. This paradigm shift enables personalised, complication-focused care and positions GLP-1 receptor agonists (GLP-1RAs) as disease-modifying therapies rather than simple weight-loss agents.

      Why ABCD Matters?

      Traditional BMI-centric definitions fail to capture fat distribution, metabolic risk, and downstream complications. Global consensus statements now define obesity as a chronic disease requiring long-term management. In India, rising rates of generalised and abdominal obesity often at lower BMI thresholds underscore the need for this more nuanced approach.

      The ABCD model evaluates:

• Adiposity: quantity, distribution, and function of fat
• Context: behavioural, environmental, and socioeconomic drivers
• Burden: severity of obesity-related complications

      This approach supports earlier intervention and more accurate risk stratification.

      Pathophysiology: From Adiposity to Multisystem Disease

      Dysfunctional adipose tissue promotes chronic inflammation, insulin resistance, ectopic fat deposition, and altered gut-hormone signalling. These changes drive a spectrum of conditions including type 2 diabetes (T2D), cardiovascular disease (CVD), hypertension, dyslipidaemia, MASLD, chronic kidney disease (CKD), PCOS, and heart failure with preserved ejection fraction (HFpEF).

      GLP-1 Receptor Agonists: A Cornerstone Therapy

      GLP-1RAs directly address the pathophysiology of ABCD by:

• Enhancing glucose-dependent insulin secretion
• Suppressing appetite via central pathways
• Reducing visceral and ectopic fat
• Improving lipid profiles, blood pressure, and inflammatory markers

      Beyond glycaemic control, GLP-1RAs deliver pleiotropic benefits across all eight ABCD pillars, including obesity, T2D, CVD/HF, MASLD, PCOS/infertility, CKD, hypertension, and dyslipidaemia.

      Clinical Impact Across ABCD Pillars

• Type 2 Diabetes: Sustained HbA1c reduction, weight loss, and β-cell preservation; semaglutide shows “very high efficacy” for both glycaemic and weight outcomes.
• Cardiovascular Disease: Significant reductions in major adverse cardiovascular events (MACE), blood pressure, and residual cardiovascular risk.
• HFpEF: Weight loss and improved functional status, particularly in obesity-driven HFpEF phenotypes.
• MASLD: Reduction in hepatic steatosis and inflammation; high rates of disease resolution in clinical trials.
• PCOS: Improved weight, insulin resistance, menstrual regularity, and fertility-related outcomes.
• CKD: Slower eGFR decline, reduced albuminuria, and lower risk of kidney disease progression.

      Oral Semaglutide: Expanding Access

      While injectable GLP-1RAs face barriers in low- and middle-income settings, oral semaglutide improves accessibility by eliminating injection-related stigma and cold-chain requirements. Real-world and trial data confirm meaningful reductions in HbA1c, body weight, and cardiometabolic risk with a favourable safety profile.

      Prioritising GLP-1RAs in Practice

      Guidelines recommend early use of GLP-1RAs in individuals with BMI ≥25–27 kg/m² and obesity-related complications, particularly when lifestyle measures alone are insufficient. Their integration with lifestyle therapy and, when appropriate, SGLT2 inhibitors offers comprehensive risk reduction.

      Challenges and Future Directions

      Cost, access, and health-system limitations remain key challenges, especially in resource-constrained settings. Strategies such as inclusion in national formularies, price negotiations, oral formulations, and decentralised care models are essential to maximise population-level benefit.

      Key Takeaway

      The ABCD framework transforms obesity care from weight-centric management to holistic, complication-focused disease modification. Within this model, GLP-1 receptor agonists particularly oral Semaglutide emerge as foundational therapies, delivering sustained metabolic, cardiovascular, renal, hepatic, and reproductive benefits well beyond weight loss.