GLP-1 agonists: Uses, common brands, and safety info

Diabetes and obesity are two of the most impactful disorders to the health of our society. The American Diabetes Association estimates that over 10% of our population has diabetes. The Centers for Disease Control and Prevention (CDC) estimate the prevalence of obesity at over 40%. There is a significant correlation between obesity and diabetes. Obesity is a risk factor for the development of diabetes, and the CDC estimates that 30% of overweight Americans have diabetes.

Diabetes and obesity can have a significant effect on both healthcare costs and the cost of living. The medical cost of diabetes is estimated at almost $150 million in the United States.  People who are overweight have a higher incidence of other disorders including high blood pressure, heart failure, cancer, and diabetes. Fortunately, there have been significant medical advancements in the treatment of both diabetes and obesity in recent years thanks to numerous clinical trials. Glucagon-like peptide-1 receptor agonists (GLP-1) are a unique class of drugs with approved indications to treat both diabetes and obesity. Here we will discuss the different types of GLP-1 agonists, the way they work, and their side effects and safety profiles.

Other GLP-1 agonists

• Tanzeum (albiglutide)

• Byetta (exenatide)

What are GLP-1 agonists?

Glucagon-like peptide-1 receptor agonists are glucose-lowering medications used in the treatment of Type 2 diabetes, obesity, and cardiovascular risk reduction. Type 2 diabetes is a condition that causes elevated blood glucose, or hyperglycemia. The body of a patient who has Type 2 diabetes typically doesn’t make enough insulin naturally to control their blood glucose levels, or the insulin they do make doesn’t function as it should. GLP-1 agonists activate the GLP-1 receptor in the pancreas which enhances insulin output. GLP-1 agonists also have an effect on GLP-1 receptors in the central nervous system which have been shown to decrease appetite and delay the emptying of your stomach after you ingest food. GLP-1 agonists are considered a second-line therapy and are used in combination with other antidiabetic therapy such as metformin, sulfonylureas, thiazolidinediones, or basal insulin. 

How do GLP-1 agonists work?

Glucagon-like peptide-1 receptor agonists are sometimes referred to as incretin mimetics because they mimic natural incretin hormones in your body. The GLP-1 incretin hormone in your body is normally released after the consumption of dietary carbohydrates and fats. Patients with Type 2 diabetes have decreased or insufficient GLP-1. These incretin mimetic medications enhance insulin secretion, suppress glucagon secretion, slow gastric emptying, reduce appetite,  and promote an increase in beta cells, the specific cells of the pancreas where insulin is secreted from. The effects of GLP-1 agonists lead to improved glycemic control.

What are GLP-1 agonists used for?

• Type 2 diabetes mellitus (All GLP-1 agonists)

• Obesity [Saxenda (liraglutide), Wegovy (semaglutide)]

• Cardiovascular risk reduction [Trulicity (dulaglutide), Saxenda (liraglutide), Wegovy (semaglutide)]

• Weight management [Saxenda (liraglutide), Wegovy (semaglutide)]

Types of GLP-1 agonists

Oral GLP-1 receptor agonists

There is only one oral form of a GLP-1 agonist on the market, Rybelsus (semaglutide). Rybelsus, an oral semaglutide formulation, is only approved for the treatment of Type 2 diabetes in combination with diet and exercise. Oral semaglutide is not approved in the reduction of cardiovascular disease or the treatment of obesity or weight management.  

Example of oral GLP-1 agonist: 

• Semaglutide

Short-acting injectable GLP-1 receptor agonists

Short-acting injectable GLP-1 agonists are subcutaneous injections dosed either once or twice daily. How often a GLP-1 agonist must be dosed is mostly determined by the half-life of a drug. The half-life is a term that refers to how quickly or slowly the body metabolizes and excretes a drug. Short-acting GLP-1 agonists have a shorter half-life and are eliminated more quickly than their long-acting counterparts. Short-acting GLP-1 agonists are best suited for patients whose blood sugars are high after meals, also known as postprandial hyperglycemia.

Example of short-acting GLP-1 agonists: 

• Exenatide

• Lixisenatide

Long-acting injectable GLP-1 receptor agonists

Long-acting injectable GLP-1 agonists offer the advantage of once-weekly dosing because they have a longer half-life. This is important because many times patients on GLP-1 agonists are on other injectable drugs like insulin, and this decreases the number of daily injections. The mechanism of action of long-acting and short-acting GLP-1 agonists is the same, and the biggest difference is how frequently they have to be dosed. Long-acting GLP-1 agonists are better suited for patients who have a high fasting blood glucose level.

Example of long-acting GLP-1 agonists: 

• Albiglutide

• Dulaglutide

• Semaglutide

Who can take GLP-1 agonists?

Can adults take GLP-1 agonists?

Women and men can safely take GLP-1 agonists assuming their kidney function is normal. Some GLP-1 agonists do need dose adjustments in patients with kidney disease or decreased renal function. 

Can women take GLP-1 agonists while pregnant or breastfeeding?

Using any GLP-1 for weight loss or obesity treatment during pregnancy is contraindicated as the potential for harm to the fetus from weight loss during pregnancy. Prescribing of Saxenda (liraglutide) requires adequate contraception methods to ensure it is not used in pregnancy. There may be rare instances where the use of a GLP-1 agonist will be recommended in a pregnant patient to control blood sugar, but overall, the use of human insulin is the preferred treatment for diabetes in pregnant patients. Endocrinology and obstetric specialists may work together to determine what is best for the patient.

Can children take GLP-1 agonists?

Victoza (liraglutide) and Bydureon BCise (exenatide extended-release) are the only approved GLP-1 agonists for use in children who have a diagnosis of Type 2 diabetes and are at least 10 years of age. GLP-1 agonists should not be used in children for any other indications such as weight loss or improved cardiovascular outcomes.

Can seniors take GLP-1 agonists?

Because older patients are at an increased risk to experience decreasing renal function, they must be monitored closely when on GLP-1 agonists. Dose adjustments need to be made for most GLP-1 agonists when kidney function is decreased. Generally, long-acting GLP-1 agonists would be safer in the older population.

Are GLP-1 agonists safe?

Recalls

No active recalls at this time.

Restrictions

Do not take GLP-1 agonists if you have ever had a hypersensitivity reaction to any other GLP-1 agonists. 

GLP-1 agonists have been shown to cause gastrointestinal side effects early in treatment. Typically these are transient and resolve without intervention. Slow titration of dosing helps to ease these effects. Patients with pre-existing gastrointestinal diseases however may experience more frequent and severe side effects due to the use of GLP-1 agonists. Long-acting GLP-1 agonists may be the best option for patients with pre-existing stomach disorders if GLP-1 therapy is necessary as they are linked to a lesser incidence of side effects.

There is a risk of a patient’s blood sugar levels going too low with the use of GLP-1 agonists. This is known as hypoglycemia. This risk is very low, but it is increased by concurrent use with insulins and sulfonylureas.

There is a chance that the slowed rate of gastric emptying could affect the absorption of other drugs or agents. Your prescriber should consider this when prescribing oral medications.

After initiation of GLP-1 agonists, patients should monitor for signs and symptoms of pancreatitis. These include upper abdominal pain (especially if it radiates to your back or is worse after eating), abdominal tenderness, fever, rapid heart rate, nausea, and vomiting. Seek help immediately if these symptoms occur.

GLP-1 agonists carry a black box warning from the Food and Drug Administration (FDA). This warning is in regards to the use of GLP-1 agonists in patients with a personal or family history of certain types of thyroid cancer known as thyroid C-cell tumors or medullary thyroid carcinoma.

Other patient populations who should not use GLP-1 agonists or use them cautiously include those with a history of angioedema, multiple endocrine neoplasia syndrome Type 2 (MEN 2), or thrombocytopenia.

GLP-1 agonists are not approved in the treatment of Type 1 diabetes. Type 1 diabetes is different from Type 2 in that the patient’s body is not capable of producing insulin. 

Diabetes treatment with biguanides or other diabetes drugs does not negate the need for regular diabetes care and check-ups regarding feet, eyes, and kidneys. Diabetes can have dangerous effects on other organs and these should be monitored closely.

Are GLP-1 agonists controlled substances?

No, GLP-1 agonists are not controlled substances.

Common GLP-1 agonists side effects

• Constipation

• Diarrhea

• Dyspepsia

• Hypoglycemia

• Injection site reaction

• Nausea

• Vomiting

• Abdominal pain

• Gastroesophageal reflux (GERD)

• Dizziness

• Eructation

• Fatigue

• Headache

• Anorexia

How much do GLP-1 agonists cost?

Unfortunately, GLP-1 agonists are not available generically at this time. They are all single source, brand-name products. Insurance coverage may vary greatly by the plan. Most plans will cover at least one type of GLP-1 agonist for the treatment of Type 2 diabetes. It is not uncommon for a plan to have a formulary restriction where only certain GLP-1 agonists are covered. Your insurance can provide more information on your formulary coverage. Saxenda and Wegovy, approved for the treatment of obesity and weight loss, may have even more limited coverage than GLP-1 agonists used for Type 2 diabetes.

If your plan offers no coverage or you are uninsured, SingleCare could provide significant cost savings through prescription savings coupons. Be sure to ask your pharmacist to check your SingleCare coupon before finalizing your purchase of these medications.