Diabetes mellitus independently increases the risk of and mortality from heart failure in a manner that is well established but inadequately understood. Glycemic optimization does not eliminate this risk, and measures of glycemic control are insufficient markers of cardiovascular risk. In response to a regulatory guidance from the US Food and Drug Administration, glucose-lowering agents are now routinely evaluated in large cardiovascular outcome trials. These recent trial experiences of novel and established glucose-lowering therapies have shown variable risks and benefits with respect to heart failure. Cardiovascular outcome trials have increasingly included heart failure events as either a component of the primary end point or a secondary adjudicated end point. We comprehensively review each established and novel currently marketed glucose-lowering therapy, their biological targets, mechanisms of action, and relationships with heart failure. We then highlight gaps in available evidence and directions for future research regarding the ascertainment of heart failure-related data in the evaluation of emerging glucose-lowering therapies.

糖尿病独立地增加心力衰竭的风险和死亡率，其方式已得到充分证实但尚未充分了解。血糖优化并不能消除这种风险，并且血糖控制措施不足以作为心血管风险的标志。为了响应美国食品和药物管理局的监管指导，降糖药物现在在大型心血管结果试验中进行常规评估。最近的这些新型和已建立的降糖疗法的试验经验显示了与心力衰竭有关的不同风险和益处。心血管结局试验越来越多地将心力衰竭事件作为主要终点或次要判定终点的组成部分。我们全面回顾了目前上市的每一种已建立的和新颖的降糖疗法、它们的生物学靶点、作用机制以及与心力衰竭的关系。然后，我们强调了在评估新兴降糖疗法时确定心力衰竭相关数据方面现有证据和未来研究方向的差距。