MPA | Pharmacy News

By Matthew Hecker, Pharm.D., PGY1 pharmacy practice resident, Sparrow Hospital, Lansing

 

Glucagon-like-peptide-1 (GLP-1) receptor agonists are a class of injectable and oral medications used in the treatment of type II diabetes. Injectable agents that are currently approved for use in the United States are: albiglutide (Tanzeum®), dulaglutide (Trulicity®), exenatide extended release (Bydureon®), exenatide immediate release (Byetta®), lixisenatide (Adlyxin®), and liraglutide (Victoza®). Combination products containing long acting (basal) insulin include: insulin degludec/ liraglutide (Xultophy®, and insulin glargine/lixisenatide (Soliqua®). GLP-1 agents are associated with increased glucose-dependent insulin secretion, decreased inappropriate glucagon secretion, increased B-cell growth and replication, slower gastric emptying and decreased food intake.


GLP-1 agonists have been shown to lower the hemoglobin (Hb) A1C in type II diabetes by one to 1.5 percent, which is only surpassed by the lowering effects of insulin therapy. In addition to its glucose lowering effects, the results from the LEADER trial (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results) have demonstrated that liraglutide (Victoza®) can provide additional cardiovascular benefits in patients with type II diabetes.4  The overall benefits of these agents in patients with type II diabetes is seen in their outpatient utilization.


While concerns exisit for therapy in all patients, inpatient concerns for GLP-1 agonists include their use in patients with renal impairment, hypersensitivity reactions to any GLP-1 products, a history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2, and pancreatitis. The most commonly reported adverse drug effects are hypoglycemia, diarrhea, nausea and injection site reactions.1

 

Table 1: Characteristics of Injectable GLP-1 Agonists/Combination Products 1,2

Agent

 

Effect on HbA1C

Weight Loss

Hypoglycemia

Diarrhea

Nausea

Injection Site Reactions

Albiglutide

~1%

~1 kg

3-17%

13%

11%

18%

Dulaglutide

~1.5%

~2.5 kg

3-6%

9-13%

12-21%

0.5%

Exenatide ER

~1.5%

~2.5 kg

4-11%

1-20%

11%

17%

Exenatide IR

~1%

~2 kg

4-11%

11%

11%

13-17%

Liraglutide

~1.5%

~2.5 kg

16%

10-12%

20%

18%

Lixisenatide

~1%

~2 kg

n/a

8%

25%

18%

Degludec/ Liraglutide

~1% more than insulin degludec

~2.5 kg

 

Refer to Individual Agents

 

Insulin Glargine/ Lixisenatide

~0.5% more than insulin alone

~1.4 kg

 

Refer to Individual Agents

 

 

According to the American Diabetes Association (ADA), a review of anti-hyperglycemic medications concluded that GLP-1 receptor agonists show promise in the inpatient setting; however, proof of safety and efficacy await the results of randomized controlled trials. 3 There are potential administration concerns that could arise as a result of nursing staff’s unfamiliarity with these agents and their ability to cause hypoglycemia. Furthermore, cost of the medication may also be prohibitive in the inpatient setting.  Medication-related concerns such as renal impairment and gastrointestinal symptoms pose unique challenges in the acutely ill patient.


Although studies have shown that patients are able to improve glycemic control while taking these agents, there is relatively low benefit to using these agents in the acute inpatient setting.3 Patients can be sufficiently controlled with the use of basal and bolus insulin. Because of the potential risks associated with the GLP-1 agonists, the Pharmacy & Therapeutics Committee at Sparrow Hospital has classified these agents as non-formulary (Do Not Stock/Do Not Dispense). An automatic hold on GLP-1 agonists for the duration of hospitalization will occur, and providers will be prompted to utilize the basal and bolus insulin order set. Patients on combination products will be converted to basal insulin products based upon the recommended conversions provided in Table 2.

 

Table 2: Converting Combination Products to Long Acting Insulin Regimens at Sparrow 1

Combination Product

Conversion to Insulin Only Regimen

Degludec/ Liraglutide (Xultophy®)

Convert current insulin degludec dose to equivalent insulin detemir dose (Levemir®) 1:1 conversion of degludec to detemir

Insulin Glargine/ Lixisenatide (Soliqua®)

Convert current insulin glargine dose to equivalent insulin detemir dose (Levemir®) 1:1 conversion of degludec to detemir

 

 

References:

  1. Lexi-Drugs. Lexicomp Online. Hudson, OH: Wolters Kluwer Clinical Drug Information Inc. http://online.lexi.com. Accessed December 20, 2017.
  2. Therapeutic Research Center. Comparison of GLP-1. http://pharmacistsletter.therapeuticresearch.com/pl/ArticlePDF.aspx?&DocumentFileID=0&DetailID=340201&SegmentID=0. January 2017.
  3. American Diabetes Association (ADA). 14. Diabetes care in the hospital. Diabetes Care. 2017c;40(suppl 1):S120–S127.
  4. Marso SP, Daniels GH, Brown-Frandsen K et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2016;375(4):311-22.

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