Simplify type 2 diabetes regimens in geriatrics

Adjust or deprescribe medications as A1C goals are relaxed. Avoid glyburide (Diavance, Daonil) and glimepiride (Amaryl), they're on the Beers Criteria
Abdelwahab Ward, BS Pharm, PharmD

More than 1 in 4 patients over 65 have type 2 diabetes. Individualize care by focusing on health status, not just age. So, follow these simple steps...

          Focus on avoiding hypoglycemia. It's linked to an increased risk of falls, cognitive decline, and death. Explain that in many older adults, these risks often outweigh benefits of tight glucose control.

Reassess A1C goals often and resist overtreatment. Consider keeping current goals for healthier, independent older adults especially if they're doing well. But relax goals for others. For example, consider an A1C goal under 8% for those with multiple comorbidities or an even looser goal for frail elderly, severe dementia patients, nursing home residents, etc. Adjust or deprescribe medications as A1C goals are relaxed. Avoid glyburide (Diavance, Daonil) and glimepiride (Amaryl), they're on the Beers Criteria (see PDF available at: https://dcri.org/wp-content/uploads/2016/11/2012AGSBeersCriteriaCitations.pdf) due to risk of hypoglycemia. If a sulfonylurea is preferred because of cost, consider glipizide at a starting dose of 2.5 mg/day.

If insulin is needed, give basal insulin in the AM instead of PM, lower any mealtime doses and avoid sliding scales. Continue to rely on metformin (Glucophage). It can be continued in stable kidney disease down to an estimated glomerular filtration rate (eGFR) of 30 mL/min.

Consider GLP-1 agonists or SGLT2 inhibitors for potential non-glycemic benefits, if patients can tolerate and afford them. Keep in mind, certain GLP-1 agonists (Victoza, etc) decrease risk of CV events and seem to slow progression of nephropathy. Feel comfortable continuing these medications in older CV patients, if they can use a pen device. Or SGLT2 inhibitors (Jardiance, etc) may reduce risk of CV events, heart failure, and nephropathy. Lean toward continuing these in older adults with CV disease or CV risks. Warn about dizziness and hypotension. DPP-4 inhibitors (Januvia, etc) have low hypoglycemia risk, but they're reasonable to deprescribe when loosening A1C goals.

Table (1). Medications Used to Treat Hyperglycemia and Special Concerns With Use in Older Patients With CKD and CVD
Medication Class Use in Older Patients Use in Patients With CKD (Stages 3 to 5) Use in Patients With CVD
Insulin Can cause hypoglycemia Decreased clearance. Increased risk of hypoglycemia. Dosages may need adjusting. Consider giving rapid-acting insulin postprandially because of gastroparesis. May worsen fluid retention when used with thiazolidinediones. Hypoglycemia to be avoided because of potential arrhythmias and stroke
Metformin Can cause gastrointestinal intolerance Reduce dosage to 1000 mg/d if eGFR <45; do not start if eGFR <45 May be beneficial in patients with coronary artery disease. Avoid use in patients with severe CHF to avoid lactic acidosis
Does not cause hypoglycemia Stop if eGFR <30
May cause vitamin B12 deficiency Stop if increased risk of acute kidney injury (radiocontrast dye, hypotension, sepsis, shock, hypoxia).
SUs Can cause hypoglycemia Glyburide: avoid if eGFR <60 Can cause hypoglycemia, which is to be avoided because of potential arrhythmias and stroke
Can cause weight gain Glimepiride: avoid if eGFR <30
Avoid glyburide Glipizide: use with caution if eGFR < 30
Glinides Can cause hypoglycemia Nateglinide: stop if eGFR <60 but can use if patient is on dialysis Can cause hypoglycemia, which is to be avoided because of potential arrhythmias and stroke
May be useful for individuals who skip meals Repaglinide: use with caution if eGFR <30
Thiazolidinediones Does not cause hypoglycemia No dosage adjustment needed. Can cause fluid retention. Can increase fractures. Pioglitazone has been shown to reduce CVD mortality. Can cause fluid retention with potential to worsen heart failure
Can increase fracture risk
Can cause fluid retention
Can cause weight gain
α-Glucosidase inhibitors Does not cause hypoglycemia Avoid if serum creatinine >2.0 mg/dL because of lack of studies in such patients
Gastrointestinal side effects may cause nonadherence
DPP-4 inhibitors Does not cause hypoglycemia Sitagliptin: Saxagliptin has been shown to increase the risk of heart failure
 eGFR >50: 100 mg/d
 eGFR 30–50: 50 mg/d
 eGFR <30: 25 mg/d
Saxagliptin:
 eGFR >50: 2.5 or 5 mg daily
 eGFR ≤50: 2.5 mg daily
Alogliptin:
 eGFR >60: 25 mg daily
 eGFR 30–60: 12.5 mg daily
 eGFR <30: 6.25 mg daily
Linagliptin:
 No dosage adjustment needed
SGLT2 inhibitors Does not cause hypoglycemia Canagliflozin: eGFR 45–60: 100 mg/d; eGFR <45: avoid use Empagliflozin and canagliflozin have been demonstrated to reduce major adverse cardiovascular events and CHF
Empagliflozin can reduce cardiovascular events and progression of CKD Dapagliflozin: eGFR <60: avoid use
Volume depletion adverse effects more common in older patients Empagliflozin: eGFR <45: avoid use
Ertugliflozin: eGFR <60: avoid use
Canagliflozin may increase fracture risk; has also been associated with an increased risk of toe and foot amputations Canagliflozin and dapagliflozin have been associated with acute kidney injury
May rarely cause ketoacidosis Empagliflozin and canagliflozin can reduce progression of CKD
GLP-1 receptor agonists Does not cause hypoglycemia Exenatide: eGFR <30: avoid use Liraglutide and semaglutide have been demonstrated to reduce major adverse CVD events
May cause gastrointestinal side effects Liraglutide, dulaglutide, semaglutide: no dosage adjustment needed
Lixisenatide: avoid if eGFR <15
Bromocriptine May cause nausea Use with caution. Not studied in CKD.
Does not cause hypoglycemia
Colesevelam May cause gastrointestinal side effects No dosage adjustment needed, but limited data are available
Reference from, J Clin Endocrinol Metab . 2019 May 1;104(5):1520-1574. doi: 10.1210/jc.2019-00198.

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Abdelwahab Ward, BS Pharm, PharmD