The beneficial effects of beta blockers in younger patients with heart failure (HF) due to systolic dysfunction are well established. However, data from patients > or =70 years old with diabetes mellitus and HF are lacking. The Study of Effects of Nebivolol Intervention on Outcomes and Rehospitalization in Seniors with heart failure [SENIORS] tested the efficacy of the vasodilator beta blocker nebivolol in patients > or =70 years old with HF and impaired or preserved left ventricular ejection fraction. In the present analysis, we evaluated the association between diabetes mellitus and baseline glucose levels on the primary outcome (all-cause mortality and cardiovascular hospitalization) and secondary end points, including all-cause mortality, cardiovascular hospitalizations, and cardiovascular mortality. Of 2,128 patients, 555 (26.1%) had diabetes mellitus. Of the 555 patients with diabetes mellitus, 223 (40.2%) experienced the primary end point compared to 484 (30.8%) of the 1,573 nondiabetic patients (p <0.001). For the nondiabetic patients, the rate of the primary outcome for placebo compared to nebivolol was 33.7% for the placebo group and 27.8% for the nebivolol group (hazard ratio 0.78, 95% confidence interval 0.65 to 0.93; p = 0.006). In the diabetic subset, the rate was 40.3% for the placebo group and 40.1% for the nebivolol group (hazard ratio 1.04, 95% confidence interval 0.80 to 1.35, p = 0.773). The subgroup interaction p value was 0.073. The baseline glucose levels in the nondiabetic patients did not significantly affect the outcomes. The effect of diabetes mellitus on outcome was independent of the left ventricular ejection fraction and was most pronounced in those with HF due to a nonischemic etiology. In conclusion, in patients > or =70 years old with HF, diabetes mellitus was associated with a worse prognosis. Nebivolol was less effective in the patients with diabetes and HF than in those with HF but without diabetes who were > or =70 years old.