Recent trials underscore the cardiovascular (CV), renal, and metabolic benefits of semaglutide in individuals with and without type 2 diabetes (T2D). In T2D, semaglutide enhances glycemic control, reduces major adverse CV events (MACE), and slows chronic kidney disease (CKD) progression. The SUSTAIN-6 trial demonstrated a 26% MACE reduction (HR 0.74; 95% CI: 0.58-0.95; = 0.02) in high CV-risk patients with T2D using semaglutide (0.5 or 1.0 mg weekly). Similarly, the FLOW trial showed a 24% reduction in major kidney disease events (HR 0.76; 95% CI: 0.66-0.88; = 0.002) with weekly 1.0 mg semaglutide in individuals with T2D with CKD. Beyond T2D, the SELECT trial highlighted semaglutide's efficacy in reducing MACE by 20% (HR 0.80; 95% CI: 0.72-0.90; < 0.001) and slowing kidney function loss in overweight or obese individuals with preexisting CV disease using 2.4 mg weekly. Additionally, semaglutide alleviates heart failure symptoms and reduces hospitalizations in obese individuals regardless of T2D status. These findings underscore semaglutide's role in improving kidney, CV, and survival outcomes among high-risk patients. This review highlights the cardio-kidney-metabolic benefits of semaglutide in individuals with and without T2D to inform cardiologists about its potential to enhance patient care.