TABLE 5.

Oral and Noninsulin Injectable Medications for Type 2 Diabetes and Considerations Related to Cognitive Impairment

MedicationAdvantages in Cognitive ImpairmentPossible Disadvantages in Mild Cognitive ImpairmentPossible Disadvantages in DementiaOther Considerations
Metformin• Oral medication; easy to use; inexpensive
• Once-daily dosing (with extended release preparations)
• Very low risk of hypoglycemia
• None specific to cognitive impairment
• May cause GI side effects, reduced appetite
• None specific to dementia
• May cause GI side effects, reduced appetite
• Vitamin B12 deficiency possible
• Use with caution if age is >80 years, with attention to need for dose adjustment for renal insufficiency; do not use if GFR <30 mL/min/1.73 m2
Sulfonylureas
(glipizide, glimepiride,
glyburide)
• Oral medication; easy to use; inexpensive
• Once-daily dosing possible
• Risk of hypoglycemia
• Glipizide is associated with lowest risk of hypoglycemia
• Avoid glyburide because of increased risk of prolonged hypoglycemia
• Risk of hypoglycemia increased with unreliable food intake (low-dose glipizide preferred)
• Hypoglycemia risk increased with poor or unreliable intake of food
• Avoid glyburide because of increased risk of prolonged hypoglycemia
Meglitinides
(repaglinide, nateglinide)
• Oral medication; easy to use
• Mealtime dose can be held if the patient skipped the meal or ate a small meal
• Risk of hypoglycemia (but less than with sulfonylureas)
• May be difficult to remember multiple daily dose regimen
• Risk of hypoglycemia
• Three-times-daily mealtime dosing; would require involvement of a caretaker
• Possible advantage of flexibility in patients with irregular eating habits; would require involvement of a caretaker
DPP-4 inhibitors
(sitaglipitin, saxagliptin, linagliptin, alogliptin)
• Oral medication; easy to use
• Once-daily dosing
• Very low risk of hypoglycemia
• None specific to cognitive impairment• None specific to cognitive impairment• Expensive
• May need to adjust dose based on renal function
GLP-1 receptor agonists (exenatide, liraglutide, albiglutide, dulaglutide)• Twice-daily, daily, or weekly dosing
• Weekly dosing in particular might help simplify medication regimen
• Injectable only; delivery devices may be difficult to use
• Weekly dosing can be hard to remember
• Can contribute to hypoglycemia when used with insulin or a sulfonylurea
• GI side effects, especially nausea, and weight loss may limit use
• Injection devices would likely require involvement of a caregiver
• Can contribute to hypoglycemia when used with insulin or a sulfonylurea
• GI side effects, especially nausea, and weight loss may limit use
• Expensive
TZDs
(pioglitazone, rosiglitazone)
• Oral medication; easy to use
• Once-daily dosing possible
• Low risk of hypoglycemia
• None specific to cognitive impairment• None specific to cognitive impairment• Use with caution in the elderly due to possible increased fluid retention, exacerbation of heart failure, and increased risk of fractures
α-Glucosidase inhibitors (acarbose, miglitol)• Oral medication; easy to use
• Low risk of hypoglycemia
• May be difficult to remember multiple daily dose regimen• Possible advantage of flexibility in patients with irregular eating habits; would require involvement of a caretaker• GI side effects of diarrhea, flatulence, and abdominal pain may limit use
SGLT2 inhibitors
(canagliflozin, dapagliflozin, empagliflozin
• Oral medication; easy to use
• Once-daily dosing
• Low risk of hypoglycemia
• Dehydration may worsen cognition and cause dizziness or lightheadedness, increasing fall risk
• Risk of UTIs, which may worsen cognition
• Decreased fluid intake could lead to intravascular volume depletion (increasing fall risk) and renal impairment
• Risk of UTIs and addition of delirium to dementia
• Expensive
• Worsening of urinary incontinence
• Risk of DKA (especially if insulin is also required)