In a meta-analysis of 8 ran- domized, controlled trials (that included a total of 37229 patients) comparing more with less intensive glucose- lowering strategies, the risk of HF-related events did not differ significantly between more intensive regimens and standard therapy despite achieving an average HbA1c In subgroup analyses limited to clinical trials specifically designed to compare strategies targeting more intensive and standard glycemic control (VA-CSDM [Veterans Affairs Cooperative Study on Glycemic Control and Complications in Type II Diabetes] Feasibility, UKPDS [United Kingdom Prospective Diabetes Study], ADVANCE [Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation], ACCORD [Action to Control Cardiovascular Risk in Diabetes], and VADT [Vet- erans Affairs Diabetes Trial]), intensive glucose-lowering strategies were not associated with a reduced risk of HF compared with standard regimens (odds ratio, 1.02; Glycemic Control and Outcomes in Patients With Established HF In patients with established HF at baseline, the relation- ship between glycemic control and outcomes has not been clearly defined. Some observational data have demonstrated a potential U-shaped or inverse relation- ship between glycemic levels (HbA1c) and mortality in in- dividuals with established HF and diabetes mellitus.123 125 In a study of 5815 ambulatory patients with HF receiving Management of Comorbidities in Chronic Heart Failure CLINICAL STATEMENTS AND GUIDELINES medical treatment for diabetes mellitus treated at Vet- erans Affairs medical centers, individuals with modest glycemic control (HbA1c >7.1% 7.8%) had lower mor- tality compared with individuals with either higher or low- er HbA1c levels (Figure 4).123 In another cohort of 123 diabetic individuals with advanced HFrEF referred to a single academic medical center, patients with an HbA1c 7.0% had significantly increased mortality compared with those with an HbA1c >7.0% (adjusted HR, 2.3; 95% In a similar study of 358 patients with advanced HFrEF and diabetes mellitus, the relationship between HbA1c levels and 2-year mortality or need for urgent transplantation was assessed with the use of 7.2%; quartile 3, 7.3% 8.5%; and quartile 4, 8.6%). 