Choosing glucose-lowering medication for patients with indicators of high risk or established ASCVD, CKD, or HF. 1Proven CVD benefit means having an indication for reduction of CVD events. 2SGLT2 inhibitor labeling varies by region and individual agent with regard to indicated level of eGFR for initiation and continued use. 3Empagliflozin, canagliflozin, and dapagliflozin have shown reduction in HF and in CKD progression. Canagliflozin has shown reduction in a composite primary renal outcome. Dapagliflozin has shown reduction in HF. 4Use caution with GLP-1 receptor agonists in ESRD. 5Degludec and U-100 glargine insulins have demonstrated CVD safety. 6Low dose may be better tolerated though less well studied for CVD effects. 7Choose later-generation sulfonylurea to lower risk of hypoglycemia. Glimepiride has shown similar cardiovascular safety to DPP-4 inhibitors. *Recommendations regarding GLP-1 receptor agonist use when ASCVD predominates, discussed in more detail on p. 8, are based on recent evidence and expert opinion; therefore, they differ slightly in emphasis from corresponding recommendations in the 2020 ADA Standards of Care. CV, cardiovascular; DPP-4i, DPP-4 inhibitor; GLP-1RA, GLP-1 receptor agonist; LVEF, left ventricular ejection fraction; LVH, left ventricular hypertrophy; SGLT2i, SGLT2 inhibitor; SU, sulfonylurea. Adapted from refs. 13 and 14.