Obesity is increasingly recognized as a chronic, relapsing, and progressive disease that acts as a major upstream driver of cardiovascular, kidney, and metabolic disorders, with South Asians experiencing heightened vulnerability at lower adiposity thresholds. Despite this, effective metabolic therapies remain underutilized in cardiology practice. Semaglutide, a GLP-1 receptor agonist, has emerged as a multisystem, disease-modifying agent with benefits that extend well beyond glycemic control. Accumulating evidence from the STEP (Semaglutide Treatment Effect in People with Obesity) program, the SELECT cardiovascular outcomes trial, the SOUL trial, heart failure with preserved ejection fraction (HFpEF) studies, and real-world cohorts underscores its relevance for cardiometabolic risk reduction and symptom improvement. Recognizing the need for India-specific guidance, a panel of cardiologists from across the country reviewed pivotal randomized trials, including STEP 1-8, STEP-HFpEF, STEP-HFpEF DM, STEP TEENS, SELECT, SOUL, SUSTAIN-6, and PIONEER-6, along with meta-analyses, observational data, and international recommendations to formulate practical, context-appropriate guidance for cardiology practice. Across diverse studies, semaglutide consistently produces substantial reductions in body weight and visceral fat, accompanied by improvements in blood pressure, glycemic control, inflammatory markers, and hepatic steatosis. SELECT demonstrated a significant reduction in major adverse cardiovascular events in adults with overweight or obesity and established atherosclerotic cardiovascular disease (ASCVD), independent of diabetes status. Benefits of obesity-related HFpEF include meaningful gains in symptoms, exercise tolerance, and quality of life. Emerging data also support renal and hepatic protection across CKM domains. Findings from high-dose 7.2 mg studies highlight a dose-response continuum but call for careful assessment of tolerability. As international guidelines increasingly position GLP-1 receptor agonists as cardiometabolic therapies, Indian data emphasize the importance of early, phenotype-driven intervention. Semaglutide represents a practice-changing therapy that addresses core pathophysiological drivers of ASCVD and HFpEF through integrated modulation of adiposity and metabolic dysfunction. Its cardiovascular efficacy, multisystem benefits, and suitability for South Asian phenotypes support broader incorporation into contemporary cardiology. This consensus offers a framework for evidence-based patient selection, contraindications, monitoring, maintenance strategies, and coordinated multidisciplinary implementation to ensure safe and effective use in Indian clinical practice.
