Sodium glucose cotransporter-2 inhibitors
SGLT-2 inhibitors prevent the reabsorption of renal-filtered glucose, resulting in decreased blood glucose levels and increased urinary excretion of glucose without stimulating insulin secretion, and therefore without increasing the risk of hypoglycemia. Additional effects include decreased blood pressure and weight loss.20 Dose adjustment is required in renal impairment.
SGLT-2 inhibitors can be used as monotherapy or in combination with other agents, including insulin, and the relatively low risk of hypoglycemia and moderate A1C lowering potential of 0.5% to 1% provide an oral option for select older patients.20 Common adverse events include hypotension, hyperkalemia, increased low-density lipoprotein (LDL) levels, acute kidney injury, genital mycotic infections, and hypoglycemia when used in combination with insulin or insulin secretagogues.20
Additional warnings have been issued by the FDA for the risk of urinary tract infection with sepsis, as well as diabetic ketoacidosis associated with SGLT-2 inhibitor use.21 The FDA has reported bone fracture risk and decreased bone mineral density with canagliflozin.21 Avoid using SGLT-2 inhibitors in patients with osteopenia or osteoporosis, as the risks outweigh the benefits. Drug-specific warnings may further impact individual use of an agent, with canagliflozin most recently having been associated with increased risk of leg and foot amputations.21
Given the adverse effect profile of SGLT-2 inhibitors, assess their risks and benefits in older patients on a case-by-case basis. Before initiating therapy, evaluate each patient’s volume status. A higher incidence of adverse effects related to intravascular volume depletion has been reported in those 65 or older, with a more prominent increase seen in patients 75 or older.22 However, the risk of hypoglycemia does not seem to increase with age.22
Although many adverse effects have been reported with SGLT-2 inhibitors, empagliflozin was associated with significantly lower rates of all-cause and cardiovascular death and lower risk of hospitalization for heart failure in the only SGLT-2 inhibitor cardiovascular outcomes trial reported to date.23 If this cardiovascular benefit is replicated in additional trials of the other SGLT-2 inhibitors, use of this drug class may increase.
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