Sitagliptin in Type 2 Diabetes Mellitus and Cardiovascular Disease: A Public Health and Health Equity Perspective

ABSTRACT: Type 2 diabetes mellitus and cardiovascular disease are interrelated conditions that disproportionately affect underserved populations, with compounded risk in communities facing systemic barriers to care. This review synthesizes clinical trial evidence, preclinical research, and public health perspectives to evaluate sitagliptin’s pharmacologic profile, safety, and potential vascular effects, particularly in resource-limited settings. Sitagliptin, the first FDA-approved oral DPP-4 inhibitor, demonstrates weight neutrality, minimal hypoglycemia risk, and renal dosing flexibility. Large cardiovascular outcomes trials confirm cardiovascular neutrality, while preclinical and animal studies suggest possible microvascular benefits. Despite superior cardiovascular outcomes with newer agents like GLP-1 receptor agonists and SGLT2 inhibitors, sitagliptin remains a practical option for patients who cannot access or tolerate these therapies, supported by oral dosing, low side-effect burden, and anticipated generic availability in the US. Its continued value is evident in U.S. safety-net systems such as federally qualified health centers (FQHCs), and globally in low- and middle-income countries where newer drugs remain unaffordable. Achieving meaningful public health impact will require pairing pharmacologic safety with structural access improvements, including expanded insurance coverage, protection of safety-net drug pricing programs, culturally tailored interventions, and inclusive research practices. Sitagliptin illustrates a broader principle in chronic disease care: even safe therapies cannot close disparities until equitable access.