Table 9.2.

Contraindicated with eGFR <30 mL/min/1.73 m²

GI side effects: mitigate with slow dose titration, extended-release formulations, and administration with food

Potential for vitamin B12 deficiency: monitor and replete as appropriate

See labels of individual agents for dosage considerations for kidney function

Glucose-lowering effect is minimal at eGFR <45 mL/min/1.73 m² and lower; continue or start for cardiovascular and kidney benefit if eGFR >20 mL/min/1.73 m². May continue until dialysis or transplantation

DKA risk in individuals with insulin deficiency (rare in T2D): discontinue, evaluate, and treat promptly if suspected; be aware of predisposing risk factors and clinical presentations (including euglycemic DKA); mitigate risk with sick-day planning; discontinue before scheduled surgery (e.g., 3–4 days), during critical illness, or during prolonged fasting

Genital mycotic infections: mitigate risk with genital hygiene and avoid use in high-risk individuals

Urosepsis and pyelonephritis: evaluate individuals for signs and symptoms of urinary tract infections and treat promptly

Necrotizing fasciitis in the perineum (Fournier gangrene): rare; prompt treatment if suspected

Intravascular volume depletion: attention to volume status and blood pressure, particularly when ill or fasting; adjust other volume-contracting agents as applicable; monitor kidney function upon initiation

See labels of individual agents for dosage considerations for kidney function

No dose adjustment for dulaglutide, liraglutide, or semaglutide

Monitor kidney function when initiating or escalating doses in individuals with kidney impairment reporting severe adverse GI reactions

Thyroid C-cell tumors identified in rodents; human relevance not determined

Provide guidance on discontinuation prior to surgical procedures to mitigate potential for pulmonary aspiration with general anesthesia or deep sedation

Pancreatitis: acute pancreatitis has been reported, but causality has not been established; do not initiate if at high risk for pancreatitis, and discontinue if pancreatitis is suspected

Biliary disease: evaluate for gallbladder disease if cholelithiasis or cholecystitis is suspected; avoid use in at-risk individuals

Ileus: reported, but risk level is not well established

Diabetic retinopathy: close monitoring of retinopathy in those at high risk (older individuals and those with longer duration of T2D [≥10 years])

Nonarteritic anterior ischemic optic neuropathy (NAION) reported (rare incidence); monitor for NAION during eye examinations

Impact on drug absorption: orally administered drug absorption may be impaired during dose titration (including oral contraceptives)

GI side effects: counsel on potential for GI side effects; provide guidance on dietary modifications to mitigate GI side effects (reduction in meal size, mindful eating practices [e.g., stop eating once full], decreasing intake of high-fat or spicy food); consider slower dose titration for those experiencing GI challenges; not recommended for individuals with gastroparesis

See labels of individual agents for dosage considerations for kidney function

No dose adjustment

Monitor kidney function when initiating or escalating doses in individuals with kidney impairment reporting severe adverse GI reactions

Dose adjustment required based on kidney function (sitagliptin, saxagliptin, alogliptin)

No dose adjustment required for linagliptin

Pancreatitis has been reported but causality has not been established; discontinue if pancreatitis is suspected

Postmarketing concerns about joint pain (consider discontinuing if debilitating and other treatment options are feasible) and bullous pemphigoid (discontinue if suspected) reversible upon discontinuation

No dose adjustment required

Generally not recommended in kidney impairment due to potential for fluid retention

Increased risk of HF and fluid retention; do not use in setting of HF

Risk of bone fractures

Bladder cancer: do not use in individuals with active bladder cancer, and use caution in those with prior history of bladder cancer; association observed with higher cumulative exposure (e.g., longer duration, higher doses)

Glyburide: generally not recommended in CKD

Glipizide and glimepiride: initiate conservatively to avoid hypoglycemia

FDA Special Warning on increased risk of CV mortality based on studies of an older sulfonylurea (tolbutamide); glimepiride shown to be CV safe (see text)

Use with caution in individuals at risk for hypoglycemia, particularly if in combination with insulin

Lower insulin doses required with a decrease in eGFR; titrate per clinical response

Injection site reactions

Higher risk of hypoglycemia with human insulin (NPH or premixed formulations) vs. analogs

Risk of hypoglycemia and duration of activity increases with severity of impaired kidney function

Refer to device-specific instructions for insulins compatible with different delivery systems (i.e., pumps, connected insulin pens, insulin patches)