Abstract Background Diabetes mellitus (DM) is a common comorbidity among heart failure (HF), complicated with 10% to 47% of HF patients. DM is also known to be associated with cardiovascular mortality and hospitalization for heart failure (HHF) in HFpEF and HFrEF. Though HbA1c is the most used glycemic control target, whether HbA1c is the most appropriate glycemic control marker remains to be investigated. Purpose To evaluate relationships between clinical outcomes and glycemic markers among heart failure patients, including HbA1c, HOMA-β and HOMA-IR. Methods We retrospectively evaluated the relationships between fasting state glycemic markers, including HbA1c, HOMA-β and HOMA-IR, and clinical outcomes in heart failure patients admitted to our hospital from 2016 to 2020. These glycemic markers were calculated from fasting blood glucose and insulin concentrations. The primary outcome was composite of all cause death or HHF. Multivariate Cox regression proportional hazards models were used to assess the relationship between glycemic markers and clinical outcomes, adjusting for age, sex, DM, BMI, ischemic etiology, eGFR, log-transformed BNP and urgent hospitalization. Results 682 patients were included in the analyses. Median age was 70 years (IQR 59 to 77 years), and 66% were male. 41% patients had left ventricular ejection fraction below 40%, and 32% had DM. The median follow-up periods were 16.5 months (IQR 4.4 to 37.3 months). HOMA-IR was independently associated with the primary outcome (HOMA-IR 1.0 to 2.5: HR1.34, 95%CI 0.79 to 2.28, p = 0.27; HOMA-IR 2.5 to 10: HR2.19, 95%CI 1.30 to 3.66, p = 0.003; HOMA-IR >10: HR2.92, 95%CI 1.61 to 5.30, p<0.001), but HbA1c and HOMA-β were not associated with the primary outcome (HbA1c 6.0 to 7.0: HR0.99, 95%CI 0.70 to 1.38, p = 0.94; HbA1c 7.0 to 8.0: HR0.80, 95%CI 0.48 to 1.34, p = 0.39; HbA1c >8.0: HR1.02, 95%CI 0.48 to 2.20, p = 0.95; HOMA-β <30: HR0.98, 95%CI 0.64 to 1.51, p = 0.94) (figure 1). Receiver-operator characteristics curve analysis revealed that HOMA-IR (AUC 0.60, 95%CI 0.55 to 0.65) had a significantly better predictive value for the primary outcome compared with HbA1c (AUC 0.56, 95%CI 0.51 to 0.61) and HOMA-β (AUC 0.51, 95%CI 0.46 to 0.56) (Figure 2). Conclusion Among fasting state glycemic biomarkers, HOMA-IR was independently associated with mortality and morbidity in HF, but HbA1c and HOMA-β were not. HOMA-IR may aid better DM managements among HF patients beyond current HbA1c targeted DM managements.Adjusted hazard ratio of glycemic markerROC analysis for the primary outcome