OBJECTIVE: The objective of this study was to assess antihypertensive and lipid-lowering treatment changes in participants receiving semaglutide 2.4 mg versus placebo across pooled populations from five Semaglutide Treatment Effect in People with Obesity (STEP) trials. METHODS: Efficacy and safety of semaglutide 2.4 mg were evaluated in the STEP clinical trials. In this post hoc analysis, STEP 1, 3, 6, and 8 (which included people with overweight or obesity) and, separately, STEP 2 and 6 (which included people with overweight or obesity and type 2 diabetes) were pooled for analysis. Changes in antihypertensive or lipid-lowering treatment intensity from randomization to end of treatment were evaluated. RESULTS: In both pooled samples, a higher proportion of participants in the semaglutide 2.4 mg group versus placebo underwent antihypertensive or lipid-lowering treatment intensity reduction by end of treatment. A smaller proportion underwent antihypertensive or lipid-lowering treatment intensification by end of treatment in the semaglutide 2.4 mg group of both samples versus placebo. In participants receiving antihypertensive or lipid-lowering medications in both samples, greater numeric reductions in body weight were observed in the semaglutide 2.4 mg group versus placebo. CONCLUSIONS: These results support a relationship between semaglutide 2.4 mg treatment of overweight and obesity and reduced need for antihypertensive and lipid-lowering treatment, facilitating treatment intensity reduction/discontinuation and abating treatment intensification.