Benefits of GLP-1 Agonists in Treating Type II Diabetes

[J.Adderton, BSN, MSN]

Glucagon-like peptide 1 (GLP-1) agonists were introduced in 2005 with the launch of Byetta (exenatide), a twice-daily injection. Since then, other GLP-1 medications have been approved and this class of drugs is quickly becoming a mainstay in the treatment of type 2 diabetes. The rise of GLP-1 agonists can be attributed to 1). the ability to lower A1c with an average drop of 0.5 to 1.0 percent 2). the benefit of weight loss and 3). low risk of hypoglycemia. In addition, Victoza is FDA approved to reduce the risk of heart-related death and stroke, which is significant due to the strong link between diabetes and heart disease.

How do they work?

GLP-1 is a naturally-occurring hormone in the body (incretin) that after eating, is released into the blood from the intestine. There are 5 key effects GLP-1 has on the body to lower sugar and reduce appetite:

• Signals the pancreas to produce more insulin
• Signals the pancreas to produce less glucagon
• Decreases glucose production in the liver
• Slows digestion in the stomach (reduces appetite)
• Reduces the brain’s hunger signals for reduced appetite

GLP-1 receptor agonists medications mimic the action of GLP-1 made naturally in your body. The GLP-1 made by the body lasts only for a few minutes, however, GLP-1 agonists last about 10 hours. This class of drugs come as a liquid and is administered by subcutaneous injection in the stomach, upper arm or thigh. How often the medication is administered depends on which one is prescribed and can range from 1-2 times daily or once a week.

GLP-1 receptor agonists currently available in the U.S. include:

• Dulaglutide (Trulicity)- weekly
• Exenatide (Byetta)- twice daily
• Exenatide extended-release (Bydureon, Bydureon BCise)- weekly
• Liraglutide (Victoza, Saxenda)- once daily
• Lixisenatide (Adlyxin)- once daily
• Insulin glargine/lixisenatide (Soliqua 100/33)- once daily
• Semaglutide (Ozempic)- Once weekly

*GLP-i agonists can be used alone or with other diabetes medications.

What are the side effects and disadvantages?

Nausea is a common side effect, especially when a person first begins the medication. Other side effects include vomiting, diarrhea, upset stomach, dizziness and headache. More severe, but less common side effects include pancreas inflammation and kidney failure in patients with kidney disease. Hypoglycemia is not a common side effect of GLP-1 agonists. However, if oral diabetic agents or insulin is taken with the GLP-1 agonists then hypoglycemia may occur.

The fact that GLP-1 agonists are injectable is a downside even though the frequency is generally less than other injectable insulins. Another barrier is cost and if the person does not have insurance coverage for GLP-1 agonists, the drugs are often too expensive for private pay. Co-pay card savings programs are available for most GLP-1 drugs if certain criteria are met. For example:

Victoza Savings Card

Trulicity Savings Card

Who should consider GLP-1 agonists?

An ideal candidate for GLP-1 agonists is a person with type 2 diabetes and their A1c is not at goal on metformin or other oral agents. The added benefit of weight loss and lower hypoglycemia risk make GLP-1 agonists a good option for those who would like to lose weight and/or are concerned about hypoglycemia.

What about GLP-1 agonist combination drugs?

There is the option for type-2 diabetics to take a combination drug that is a mix of basal insulin and a GLP-1 agonist. The benefits of taking a combination drug instead of a GLP-1 agonist or basal insulin alone include fewer side effects, greater A1c reduction, no weight gain and potential weight loss, lower risk of hypoglycemia and fewer injections. Combination drugs currently available are Soliqua (Lantus and Lyxumia) and Xultophy (Tresiba and Victoza).

About once weekly Ozempic(semaglutide)

Ozempic (semaglutide) is a particularly powerful GLP-1 agonist and became available in the U.S. in 2018. In clinical trials, Ozempic demonstrated a significant A1c reductions of nearly 2 percent and weight loss. The FDA requires a warning on Ozempic’s label addressing a slightly higher rate, 3%, of retinopathy in users in a clinical trial compared to 1.8% in the placebo group. In a recent “head-to-head trial of Ozempic and Trulicity, Ozempic demonstrated the following:

• Greater A1c reduction than Trulicity (1.8% versus 1.4%)
• Greater weight loss than Trulicity (10-14 lbs versus 5-7 lbs)

Ozempic is not a substitute for insulin and is not for use in people with type 1 diabetes or known diabetic ketoacidosis.

In summary, GLP-1 receptor agonists increase glycemic control in patients with type 2 diabetes. This class has demonstrated a low risk of hypoglycemia, promotion of weight loss and A1c reduction. Furthermore, the benefits of GLP-1 agonist to patients with Type 2 diabetes could help in reducing overall cardiovascular risk.

Are GLP-1 agonists used frequently in your area of practice?

---

Resources:

GLP-1 Agonists Medication Chart

Garber, A. (2011). Long-acting glucagon-like peptide 1 receptor agonists: A review of their efficacy and tolerability. Diabetes Care, 34(Supplement 2): S279-S284. Retrieved from http://care.diabetesjournals.org/content/34/Supplement_2/S279

[LadyT618, MSN, APRN, NP]

So, I just cleaned out my inbox of over 900 emails now that I'm on break from NP school and came across your articles (on this topic and on Diabetic Neuropathy Types). I just wanna say this is EXCELLENT information wrapped in such a nice package. THANK YOU!!! I've been recently trying to break down the differences between the varying types of diabetic medications and this is a fantastic start. Looking forward to more from you ?

[J.Adderton, BSN, MSN]

Thanks so much for positive feedback. Good luck NP school.