Initial glucose-lowering therapy for adults with type 2 diabetes mellitus with eGFR <45 mL/min/1.73 m² and glucose levels <250 mg/dL (13.9 mmol/L)

CVD: cardiovascular disease; eGFR: estimated glomerular filtration rate; GLP-1 RA: glucagon-like peptide-1 receptor agonist; SGLT2: sodium-glucose cotransporter 2.

* A GLP-1 RA with CVD and kidney benefit (ie, subcutaneous semaglutide, liraglutide, or dulaglutide) is a reasonable alternative. SGLT2 inhibitors have little glucose-lowering efficacy when eGFR is <45 mL/min/1.73 m². However, a low-dose SGLT2 inhibitor is often indicated for its cardiovascular and/or kidney protective benefits in patients with eGFR below this threshold. In patients with mild hyperglycemia, an SGLT2 inhibitor may suffice for glucose lowering, particularly when used in combination with metformin.

¶ In this population, we typically measure electrolytes and serum creatinine for calculation of eGFR 1 month after treatment initiation and every 3 to 6 months thereafter.

Δ Gastrointestinal side effects are the most common reason for metformin discontinuation. Hypoglycemia is rare with metformin monotherapy.

◊ GLP-1 RAs with demonstrated benefit in atherosclerotic CVD include subcutaneous semaglutide, liraglutide, and dulaglutide. These agents also have protective effects for kidney disease outcomes. GLP-1 RAs should be titrated slowly, with monitoring for gastrointestinal side effects, which could precipitate dehydration and acute kidney injury. Patients should be counseled about signs and symptoms of dehydration.

§ The risk of hypoglycemia with sulfonylurea or meglitinide treatment is higher in individuals with chronic kidney disease than in those with normal kidney function. Patients should be counseled about this risk and provided with clear instructions for glucose and symptom monitoring and for the treatment of hypoglycemia.