Abstract
Introduction: While glucagon-like peptide-1 receptor agonists (GLP-1 RAs) like semaglutide demonstrate cardiovascular benefits in clinical trials, their real-world impact on intermediate outcomes like blood pressure (BP) in multimorbid populations remains poorly characterized. Given the impact of various sociodemographic disparities on BP control, evaluating semaglutide's effects in a diverse cohort is essential. This study assessed the association between semaglutide use and BP outcomes in adults with coexisting hypertension, obesity, and type 2 diabetes (T2D).
Hypothesis: Semaglutide use will be associated with lower BP in adults with coexisting hypertension, obesity, and T2D.
Methods: A retrospective cohort study was conducted with survey and electronic health record data from the NIH All of Us Research Program. Adults with hypertension, obesity, and T2D were studied. Semaglutide users were compared to unexposed individuals via 1:1 nearest-neighbor propensity score matching. Matching variables included age, sex, race/ethnicity, cardiovascular and kidney disease, prior antihypertensive use, employment, and area deprivation index. BP was assessed from index date (first prescription or matched timepoint) through final measurement. Sequential multivariable linear regression models estimated associations between semaglutide use and BP. To address sociodemographic disparities, models adjusted for demographics, clinical factors such as baseline BP, and social determinants of health.
Results: The cohort included 266 adults with these comorbidities (mean age 65±10, 68% female, 80% White); 133 had received semaglutide. Exposed and unexposed groups were balanced after matching cardiovascular disease prevalence (43% vs. 41%) and antihypertensive use (96% vs. 97%). Semaglutide users had lower baseline BP (127/74 vs. 134/78 mmHg, p<0.01). Semaglutide use was associated with -6.3 mmHg (Table) lower SBP and -3.2 mmHg lower DBP over follow-up without adjustment. In fully adjusted models, SBP remained significantly lower (-2.4 mmHg), while DBP difference was not significant (-0.74 mmHg).
Conclusion: In this real-world cohort with cardiometabolic multimorbidity, semaglutide was associated with meaningful SBP reductions. This suggests GLP-1 RAs may offer BP benefits in addition to metabolic effects, supporting their use in cardiovascular risk reduction strategies, particularly for patients with concurrent hypertension, obesity, and diabetes.