Diabetes Drugs and the Older Adult Patient

There are new agents on the market for diabetes care. What is recommended for the older patient?

A brief conversation with Stephanie Yager, PharmD, and Marigel Constantiner, RPh, MSc, BCPS, CGP, CPh

Diabetes care must always be managed cautiously in the older patient. Hypoglycemia can result in poor outcomes, and older adults may display more neuroglycopenic manifestations of hypoglycemia such as dizziness, weakness, delirium and confusion. On the other hand, hyperglycemia increases dehydration, impairs vision and cognition, and increases the risk of infection.

There are several new diabetes agents on the market that have potential benefits and concerns for an older patient:

DPP4 inhibitors: sitagliptin, saxagliptin, linagliptin and alogliptin

• Benefits: 1 pill once daily, low risk of hypoglycemia, frequently well tolerated
• Concerns: majority of agents require dose adjustment in renal dysfunction, potential increase in admissions for heart failure in patients taking saxagliptin and alogliptin, and potential drug-drug interactions
• Overall, these agents are a good option for many older adults, but always require a double check to ensure the patient does not have contraindications to therapy and that the agent is dosed appropriately.

SGLT2 inhibitors: dapagliflozin, canagliflozin and empagliflozin

• Benefits: 1 pill once daily, low risk of hypoglycemia, empagliflozin approved to reduce risk of cardiovascular death in adults with type 2 diabetes mellitus and established cardiovascular disease
• Concerns: can lead to hyperkalemia, genitourinary infections, decreased bone mineral density, falls, fractures, renal insufficiency, hypovolemia and symptomatic hypotension. They have eGFR cut offs of 45-60 mL/min/1.73m for initiating therapy. These agents have a precaution for use in the elderly due increased risk of intravascular volume depletion, renal impairment and UTI. Since SGLT2 inhibitors cause polyuria, they may also exacerbate other geriatric conditions such as symptoms of benign prostatic hyperplasia or urinary incontinence. On May 16, 2017, the FDA added a black box warning to canagliflozin based on study findings that it causes an increased risk of leg and food amputations.
• Overall, these agents have significant side effects that could be harmful to an elderly patient

GLP1 agonists: exenatide (Byetta®), exenatide ER (Bydureon®), liraglutide (Victoza®), albiglutide (TanzeumTM), lixesenatide (Lyxumia®), and dulaglutide (Trulicity®). There are also new combination therapies; SoliquaTM: lixesenatide and insulin glargine, and Xultophy®: liraglutide and insulin degludec

• Benefits: significant Hgb-A1c lowering effects, could replace or delay the use of mealtime insulin for some patients, low risk of hypoglycemia, can lead to weight loss due to suppressed appetite, and liraglutide was shown to reduce cardiovascular events in patients with type 2 diabetes and a coexisting cardiovascular condition (LEADER trial). Other trials are underway to determine if other medications in this class also have cardiovascular benefits.
• Concerns: exenatide ER and albiglutide require several steps for preparation, they require daily or weekly subcutaneous injections, Byetta® must be administered prior to meals twice daily, and GLP1-insulin combination therapies could lead to dosing errors. GLP1 agonists can lead to decreased appetite, nausea, diarrhea, injection site reactions and pancreatitis. They also cost approximately $700/month, so may not be an option for patients with restricted insurance plans. These agents are either not recommended or have not been studied in severe renal impairment and chronic renal failure exacerbation cases have been reported.
• Overall, these agents may be a good option for older adults who may benefit from weight loss, are able to receive daily or weekly injections and do not have severe renal impairment. GLP1-agonists can be used as monotherapy, in addition to oral agents or insulin and in some circumstances can replace the need for mealtime insulin.

Stephanie Yager, PharmD, is an ambulatory care pharmacy resident at Cleveland Clinic’s main campus.

Marigel Constantiner, RPh, MSc, BCPS, CGP, CPh, is specialized as a drug information pharmacist and preceptor at Cleveland Clinic with a special interest in geriatrics. She can be reached at constam@ccf.org or 216.444.1126.

References:

American Diabetes Association. Older adults. Sec. 11. In Standards of Medical Care in Diabetesd2017. Diabetes Care 2017;40(Suppl. 1):S99–S104

Januvia (sitagliptin) [prescribing information]. Whitehouse Station, NJ: Merck and Co Inc; January 2017.

Jardiance (empagliflozin) [prescribing information]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc; December 2016.

FDA Drug Safety Communication: FDA confirms increased risk of leg and foot amputations with the diabetes medicine canagliflozin (Invokana, Invokamet, Invokamet XR). https://www.fda.gov/drugs/drugsafety/ucm557507.htm

Victoza (liraglutide) [prescribing information]. Plainsboro, NJ: Novo Nordisk Inc; April 2016.