Considerations for glucose-lowering medications in type 2 diabetes mellitus
| Monotherapy is usually inadequate for glycemic control |
| Medications that work by different mechanisms have additive effects for glucose control |
| Insulin therapy can be broadly used as monotherapy or in combination with other agents |
| Sodium-glucose cotransporter 2 (SGLT2) inhibitors have benefits in terms of renal failure, heart failure, and major adverse cardiovascular events (including death) |
| Some glucagon-like peptide 1 receptor agonists (liraglutide,48 dulaglutide,49 and semaglutide,50 but not lixisenatide51 or exenatide [weekly formulation])52 reduce risk of major adverse cardiovascular events |
| Comorbidities of diabetes affect the selection of glucose-lowering medications |
| In renal compromise: |
| Metformin poses risk of lactic acidosis; do not initiate if estimated glomerular filtration rate (eGFR) is < 45 mL/min/1.73 m2; but patients currently on metformin with eGFR ≥ 30 and < 45 mL/min/1.73m2 may continue cautiously, considering a 50% reduction and frequent monitoring of renal function; discontinue if eGFR is < 30 mL/min/1.73 m2 |
| Adjust dose of dipeptidyl peptidase 4 (DPP4) inhibitors |
| SGLT2 inhibitors have reduced efficacy |
| In heart failure or risk of heart failure: |
| Discontinue peroxisome proliferator-activated receptor (PPAR) gamma agonists |
| Use DPP4 inhibitors (saxagliptin, alogliptin) with caution |
| In hypoglycemia: |
| Avoid sulfonylureas |
| Adjust dose of insulin |
Based on information in references 45–52.