Version July 2025
ACEi: angiotensin-converting enzyme inhibitor; ACR: albumin-to-creatinine ratio; ARB: angiotensin receptor blocker; ASCVD: atherosclerotic cardiovascular disease; CGM: continuous glucose monitoring; CKD: chronic kidney disease; CV: cardiovascular; CVD: cardiovascular disease; CVOT: cardiovascular outcomes trial; DPP-4i: dipeptidyl peptidase 4 inhibitor; DSMES: diabetes self-management education and support; eGFR: estimated glomerular filtration rate; GLP-1 RA: glucagon-like peptide 1 receptor agonist; HF: heart failure; HFpEF: heart failure with preserved ejection fraction; HFrEF: heart failure with reduced ejection fraction; HHF: hospitalization for heart failure; MACE: major adverse cardiovascular events; MI: myocardial infarction; SGLT2i: sodium-glucose cotransporter 2 inhibitor; T2D: type 2 diabetes; TZD: thiazolidinedione.
* In people with HF, CKD, established CVD, or multiple risk factors for CVD, the decision to use a GLP-1 RA or SGLT2i with proven benefit should be independent of background use of metformin.
¶ A strong recommendation is warranted for people with CVD and a weaker recommendation for those with indicators of high CV risk. Moreover, a higher absolute risk reduction and thus lower numbers needed to treat are seen at higher levels of baseline risk and should be factored into the shared decision-making process. Refer to UpToDate content on the initial management of hyperglycemia and management of persistent hyperglycemia in adults with T2D.
Δ For GLP-1 RA, CVOTs demonstrate their efficacy in reducing composite MACE, CV death, all-cause mortality, MI, stroke, and kidney endpoints in individuals with T2D with established/high risk of CVD.
◊ For SGLT2i, CV/kidney outcomes trials demonstrate their efficacy in reducing the risk of composite MACE, CV death, all-cause mortality, MI, HHF, and kidney outcomes in individuals with T2D with established/high risk of CVD.
§ Low-dose TZD may be better tolerated and similarly effective.