Cardiovascular outcome trials of antihyperglycaemic drugs and non-statin LDL-cholesterol-lowering drugs in patients with type 2 diabetes who have, or who are at high risk of, atherosclerotic cardiovascular disease have provided new evidence that has substantially affected the management of cardiovascular risk in these patients. On the basis of proven cardiovascular and renal benefit, the antihyperglycaemic drugs empagliflozin, liraglutide, and semaglutide-the latter being under review for approval by the US Food and Drug Administration and the European Medicines Agency-should be preferentially used as second-line treatments in these patient populations, typically in addition to metformin. Further treatment differentiation among the remainder of the antihyperglycaemic drugs should be made on the basis of evidence regarding cardiovascular safety, which is available for lixisenatide, alogliptin, saxagliptin, sitagliptin, and insulin glargine. The risk of heart failure, stroke, or retinopathy, or prevalent fasting versus postprandial hyperglycaemia, could also be considered in treatment decision making. Finally, emerging evidence of cardiovascular benefit for ezetimibe, alirocumab, and evolocumab positions these drugs as add-ons to maximally tolerated statin therapy or for those with statin intolerance.
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