A few studies based on older-generation sulfonylureas have led to conflicting results for cardiovascular risk. Some evidence suggests greater risk of mortality with first-generation sulfonyl- compared with more recent ones that have been implicated in marginal cardiovascular benefit.165 These older studies have been criticized for flaws in clinical trial Although no certain cardioprotective effect or beneficial effect in HF can be attributed to sulfonylureas, newer-generation compounds have not been associated with adverse cardiovascular outcomes.165 Mechanistic differences exist between sulfonylureas. Impairment of Table 6. Recommendations for the Treatment of Diabetes Mellitus in Stage C HF: Patients With Cardiac Structural Abnormalities or Remodeling With Prior or Current Symptoms of HF Recommendations COR LOE Referenced Guideline References Physicians should control diabetes mellitus in patients with HF in accordance with recommended guidelines Caution is urged for the use of thiazolidinediones in all patients with signs and symptoms of congestive HF. Initiation of these agents is contraindicated in patients with class III or IV HF. III: Harm for NYHA class III IV HF COR indicates Class of Recommendation; HF, heart failure; LOE, Level of Evidence; and NYHA, New York Heart Association. Management of Comorbidities in Chronic Heart Failure CLINICAL STATEMENTS AND GUIDELINES cardiac ischemic preconditioning has been implicated as a reason for the potential detrimental cardiovascular effect of older-generation sulfonylureas on the basis of nonselective effects of these agents on pancreatic and cardiac K-ATPase channels. Impairment of cardiac isch- emic preconditioning does not seem to occur with more selective and newer-generation sulfonylureas.166 The incretin-based therapies (glucagon-like peptide-1 hibitors) have emerged as a new class of hyperglycemic medications. 