Background <p>Diabetes is a leading cause of morbidity and mortality in the United States. We aimed to characterize secular trends in diabetes prevalence, control of glucose and associated comorbidities, and medication use.</p> Methods <p>This was a retrospective analysis of National Health and Nutrition Examination Series data from 2001 to 2023. We focused on three outcomes: (1) prevalence of diabetes defined by known diagnosis, hemoglobin A1c ≥ 6.5%, or fasting glucose ≥ 126&#xa0;mg/dL, and among individuals with diabetes (2) control of glucose levels, low-density lipoprotein, and blood pressure and (3) medication therapy. Predictors were cycle (year) and demographics, specifically age, sex, race/ethnicity, educational level, and household income.</p> Results <p>We included 27,437 participants of whom 3467 had diagnosed diabetes and an additional 1602 had undiagnosed diabetes. Diabetes prevalence increased from 10.0% in 2001–2002 to 15.1% in 2021–2023 and was higher in men versus women, and Hispanic/Latino or non-Hispanic Black vs. non-Hispanic White participants. Glycemic control declined over time, from 61.5 to 44.9% having hemoglobin A1c &lt; 7% in 2001–2002 vs. 2021–2023; control was lower in younger participants and those with lower educational attainment. Lipid control improved over time but remained poor: 73.1% had low-density lipoprotein ≥ 70&#xa0;mg/dL in 2017–2020, and only half of these individuals were taking a statin. There were no significant changes over time in blood pressure control, with 44–56% having blood pressure ≥ 130/80&#xa0;mmHg. Other than lower lipid control in women, we did not observe differences in control of lipids or blood pressure, or in medication treatment, based on sex and race/ethnicity.</p> Discussion <p>Diabetes has increased in prevalence from 2001 to 2023 and management of hyperglycemia and associated risk factors remains inadequate.</p>