Four Facts to Remember Before Prescribing a GLP-1 Agonist

Exenatide, dulaglitide, albiglutide, liraglutide. The incretin mimetic family of medications continues to expand with these 4 agents approved in the US and more in the pipeline. There is a lot to know about glucagon-like peptide-1 (GLP-1) agonists. Find out what you've learned since 2005 when the first, twice-daily exenatide, was approved. 

1. Which of the following GLP-1 agonists is not currently approved for use with basal insulin?

A. Exenatide (Byetta)

B. Dulaglutide (Trulicity)

C. Albiglutide (Tanzeum)

D. Liraglutide (Victoza)

E. None of the above

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Answer: B Dulaglutide (Trulicity)

The other three medications (exenatide, albiglutide and liraglutide) have all been approved for concomitant use with basal insulin but have not been studied with prandial insulin. Current studies are ongoing to evaluate the safety and, in particular, the incidence of hypoglycemia when dulaglutide is used together with basal insulin.  According to the package insert for all these drugs, when being used with an insulin secretagogue or with insulin itself, the dose should be lowered. 

2. Which of the following are strict or relative contraindications to the use of some of the GLP-1 agonists?

A. Multiple endocrine neoplasia (MEN) syndrome type 2

B. Personal or family history of medullar thyroid cancer

C. Pancreatitis

D. All of the above

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Answer: D. All of the above. 

In animal studies, some of the GLP-1 agonists have been linked with the development of medullary thyroid carcinoma.  Therefore, some GLP-1 agonists are strictly contraindicated in patients with MEN syndrome type 2 or personal or family history of thyroid cancer, as these conditions can increase the risk of developing thyroid carcinomas.  Furthermore, GLP-1 agonists have not been studied in patients with a history of pancreatitis.  Because they do affect the pancreas and the relative paucity of studies, GLP-1 agonists are relatively contraindicated in this patient population as well.

3. Which of the following is true about the dosing schedule of the GLP-1 agonist?

A.  Exenatide is dosed once daily

B. Liraglutide is dosed twice daily

C. Albiglutide comes with an auto-injector

D. Dulaglutide is dosed once weekly

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Answer: D. Dulaglutide

Dulaglutide is not only dosed once-weekly but is also the only GLP-1 agonist that comes with an auto-injector, which may be important to consider, especially in patients in whom compliance or facility with self-administration is of concern.  Besides dulaglutide, albiglutide is also dosed once weekly as is the long-acting formulation of exenatide. Liraglutide continues to require daily dosing and short-acting exenatide is given twice daily. The dosing schedule for an injectable medication can often significantly impact patient compliance.

4. Which one of the following GLP-1 agonists has been associated with only benign thyroid adenomas and has no known carcinogenic effects

A. Exenatide

B. Dulaglutide

C. Albiglutide

D. Liraglutide

E. None of the above

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Answer: A. Exenatide

In animal studies, most of the GLP-1 agonists (including liraglutide, albiglutide and dulaglutide) have been associated with thyroid C-cell tumors in rodents at clinically relevant exposures.  In contrast, exenatide was associated only with benign thyroid C-cell adenomas in female rats at all doses. There was no evidence of cancerous tumors in rats at a systemic exposure of exenatide up to 95 times the human exposure.

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Are you currently prescribing GLP-1 agonists for any of your patients with type 2 diabetes?

What has your experience been in terms of efficacy? Side effects? Other comments?