Glucose-lowering medication in type 2 diabetes: Overall approach

ASCVD: atherosclerotic cardiovascular disease; CKD: chronic kidney disease; HF: heart failure; A1C: glycated hemoglobin; LVH: left ventricular hypertrophy; GLP-1 RA: glucagon-like peptide 1 receptor agonist; CVD: cardiovascular disease; SGLT2i: sodium-glucose co-transporter 2 inhibitor; CV: cardiovascular; TZD: thiazolidinedione; DPP-4i: dipeptidyl peptidase-4 inhibitor; SU: sulfonylurea; HFrEF: heart failure reduced ejection fraction; LVEF: left ventricular ejection fraction; DKD: diabetic kidney disease; CVOTs: cardiovascular outcomes trials; T2D: type 2 diabetes mellitus; eGFR: estimated glomerular filtration rate.
* Actioned whenever these become new clinical considerations regardless of background glucose-lowering medications.
¶ Most patients enrolled in the relevant trials were on metformin at baseline as glucose-lowering therapy.
Δ Proven CVD benefit means it has label indication of reducing CVD events.
◊ Low dose may be better tolerated though less well studied for CVD effects.
§ Degludec or U-100 glargine have demonstrated CVD safety.
¥ Choose later-generation SU to lower risk of hypoglycemia; glimepiride has shown similar CV safety to DPP-4i.
‡ Be aware that SGLT2i labeling varies by region and individual agent with regard to indicated level of eGFR for initiation and continued use.
† Empagliflozin, canagliflozin, and dapagliflozin have shown reduction in HF and to reduce CKD progression in CVOTs. Canagliflozin and dapagliflozin have primary renal outcome data. Dapagliflozin and empagliflozin have primary HF outcome data.
** Proven benefit means it has label indication of reducing HF in this population.
¶¶ Refer to Section 11: Microvascular Complications and Foot Care^[1].
ΔΔ Degludec/glargine U-300 < glargine U-100 / detemir < NPH insulin.
◊◊ Semaglutide > liraglutide > dulaglutide > exenatide > lixisenatide.
§§ If no specific comorbidities (ie, no established CVD, low risk of hypoglycemia, and lower priority to avoid weight gain or no weight-related comorbidities).
¥¥ Consider country- and region-specific cost of drugs. In some countries, TZDs are relatively more expensive and DPP-4i are relatively cheaper.