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.