Dipeptidyl peptidase-4 (DPP-4) inhibitors work by suppressing the enzyme that degrades 2 incretin hormones, glucagon-like peptide 1 (GLP-1) and gastric inhibitory polypeptide (GIP). The resulting enhancement of incretin activity increases glucose-dependent insulin secretion, decreases glucagon secretion, and promotes satiety.6 These agents have modest efficacy with the potential to lower A1C by 0.5% to 0.9%.8,13 Studies show that DPP-4 inhibitors are well tolerated with a minimal risk of hypoglycemia in the elderly.13 These agents are ideal for combination therapy or for monotherapy in older patients who are not good candidates for metformin or a sulfonylurea.
The safety profile, neutral effect on weight, and once-daily dosing make these agents advantageous for use in frail and debilitated elderly patients, as well as in patients with cognitive dysfunction, decreased dexterity, inconsistent meal patterns, or adherence issues. Dose adjustment is required in renal impairment, with the exception of linagliptin. High cost or formulary restrictions may impact use of these agents.
The DPP-4 inhibitors were well tolerated in short-term studies, but long-term safety has yet to be established.6 Reported post-marketing adverse effects include acute renal failure, allergic reactions, and acute pancreatitis.6,14 These agents should be avoided in any patient with a history of pancreatitis.14 In addition, trials investigating the cardiovascular safety and efficacy of DPP-4 inhibitors point to an increased risk of heart failure with the use of saxagliptin and alogliptin, regardless of age.15,16 The potential for adverse effects warrants increased patient monitoring when using these agents in older patients.
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are injectable agents that potentiate the actions of the naturally occurring incretin GLP-1, which increases glucose-dependent insulin secretion, inhibits glucagon release, reduces hepatic glucose production, and delays gastric emptying. These agents have a pronounced effect on satiety and promote weight loss. The most common adverse effects are nausea, vomiting, and diarrhea, which occur most commonly during treatment initiation and titration. Studies in elderly patients confirm A1C reductions of 1% to 1.5% and a low risk of hypoglycemia when used alone.17,18
GLP-1 RAs can be used as monotherapy in older patients at risk for hypoglycemia or in those with hypoglycemic unawareness. They can also be used in combination therapy with other agents, including insulin, though concomitant use with insulin or insulin secretagogues increases the risk of hypoglycemia.3 Weight loss and GI adverse effects may limit the use of these agents in frail or undernourished elderly patients.6
Continue to: Since these agents are injected...