What Are GLP-1 Receptor Agonists and How Do They Treat Type 2 Diabetes?

All GLP-1 RAs affect the body in similar ways, but there are some key differences between them.

GLP-1 RAs are classified as short-acting or long-acting, depending on how long they work in your body.

To determine which GLP-1 RA may work best for you, your doctor will consider your blood sugar patterns and health history.

Short-acting GLP-1 RAs

Short-acting GLP-1 RAs stay in your body for less than a day. They help control blood sugar levels after meals.

Short-acting GLP-1 RAs approved for use in the United States include:

• exenatide (Byetta)
• lixisenatide (Adlyxin)
• oral semaglutide (Rybelsus)

These medications are typically taken once or twice per day.

Long-acting GLP-1 RAs

Long-acting GLP-1 RAs continue to work for a full day or even a week after you take them. They help control blood sugar throughout the day and night.

Long-acting GLP-1 RAs approved for use in the United States include:

• dulaglutide (Trulicity)
• exenatide extended-release (Bydureon)
• liraglutide (Victoza)
• semaglutide (Ozempic)

Victoza is taken once per day. Other long-acting GLP-1 RAs are taken weekly.

Glucagon-like peptide-1 (GLP-1) is a hormone that plays important roles in regulating appetite and blood sugar levels. GLP-1 RAs mimic the actions of this hormone.

There are three main ways that GLP-1 RAs help to manage blood sugar:

• Slow stomach emptying. When digestion is slowed down, nutrients in food are released more slowly. This prevents blood sugar from spiking after a meal.
• Increase insulin production. GLP-1 RAs help your body make more insulin. This insulin is released after a meal when your blood sugar level rises.
• Reduce sugar released from the liver. The liver can release extra sugar into the blood as needed. GLP-1 RAs prevent the liver from putting too much sugar into your bloodstream.

All GLP-1 RAs are injected under the skin, except for one. Oral semaglutide is the first and only GLP-1 RA available in pill form.

Injectable GLP-1 RAs come in disposable pen injection devices. These devices use a much smaller needle tip for injection compared to a syringe. They’re designed to be easy to use with minimal discomfort.

Some pens are single-use and contain a premeasured dose of the GLP-1 RA. In other cases, you select the amount of medication to be injected.

You inject the medication just under the skin of your stomach, upper arm, or thigh.

Some types are taken once or twice per day, while others are taken once per week.

If your doctor prescribes a GLP-1 RA, they will start you at a low dose. Then you will gradually increase your dose until you reach the right amount.

GLP-1 RAs are very effective at lowering blood sugar levels, both after meals and during periods of fasting. Unlike some medications for type 2 diabetes, they’re unlikely to cause low blood sugar (hypoglycemia).

Although more research is needed, some GLP-1 RAs have also been shown to have benefits for heart health and kidney function in people with diabetes.

For example, research has shown that treatment with Ozempic, Trulicity, Rybelsus, or Victoza is linked to significant reduction in major heart problems, such as heart attacks, in people with diabetes and existing heart disease.

Studies have also found that people who took certain GLP-1 RAs had better kidney outcomes than people who took a placebo.

GLP-1 RAs commonly cause digestive side effects, such as:

• feelings of early fullness
• lower appetite
• nausea
• vomiting
• diarrhea

Many of these side effects lessen over time.

Researchers have also reported cases of thyroid C-cell cancer in rodents treated with GLP-1 RAs. This type of cancer is rare in humans, so the overall risk is considered low. But if you have a family history of thyroid tumors, make sure your doctor is aware of it.

Another potential downside of taking GLP-1 RAs is the cost of treatment. The price of GLP-1 RAs tends to be high compared with other medications for treating type 2 diabetes.

GLP-1 RAs are often prescribed in combination with other medication to treat type 2 diabetes. It’s very common for people with type 2 diabetes to take more than one type of medication to help manage their blood sugar.

Metformin is the first-line medication recommended for blood sugar management in type 2 diabetes. If metformin doesn’t work well enough on its own, a GLP-1 RA is often added to the treatment plan.

When a GLP-1 RA is prescribed along with insulin, it can increase the odds of hypoglycemia.

Because GLP-1 RAs slow digestion, they may affect how some medications are absorbed.

If you have questions or concerns about potential drug interactions, talk to your doctor or pharmacist.

Some people lose weight while taking a GLP-1 RA. This is likely due to a few factors.

The GLP-1 hormone plays a role in appetite regulation. GLP-1 RAs can cause feelings of early fullness, as well as nausea, vomiting, and diarrhea.

A higher dose of liraglutide (Victoza) is available on the market, under the brand name Saxenda. It’s marketed at the higher dose as a weight loss drug. It’s not approved for the treatment of type 2 diabetes.

GLP-1 RAs are very effective at lowering blood sugar levels in type 2 diabetes.

Many GLP-1 RAs have potential benefits for heart and kidney health, too.

Your doctor can help you understand the potential benefits and risks of taking a GLP-1 RA. They can also help you decide whether a GLP-1 RA is right for you — and which type may best meet your needs.

In T2D, the body doesn’t respond properly to insulin. This leads to high blood glucose (sugar) levels. Your primary care practitioner handles everyday health questions. They may refer you to an endocrinologist, who specializes in diabetes. Endocrinologists monitor blood glucose levels, prescribe treatments such as lifestyle changes and medication, and help manage risks for T2D complications.

Treating T2D often requires lifestyle changes. A certified diabetes care and education specialist (CDCES) is a registered nurse, physician assistant, or other health professional who has special training to help people manage diabetes. They’ll help you navigate changes to your diet, exercise, sleep schedule, or other habits to meet your treatment goals.

A well-managed diet helps regulate your blood glucose levels, may help you lose weight, and reduces your risk of diabetic complications. A registered dietitian can design a sustainable, balanced diet that can help you to manage T2D.

High blood glucose levels can damage nerves and reduce blood flow to your feet. This may lead to slow-healing infections that you might not notice, which could eventually require amputation. A podiatrist specializes in foot care. They prescribe treatment for infections as necessary and teach you how to care for your feet and conduct regular foot exams.

Diabetic retinopathy is nerve damage in the eye caused by high blood glucose levels. It can eventually lead to vision loss. It’s important to visit an ophthalmologist or optometrist for regular eye exams. These doctors specialize in eye health and may prescribe treatment like medication or surgery for eye diseases and disorders.

Many people with T2D have high blood pressure and cholesterol. All three conditions raise the risk of heart attack and stroke. A cardiologist specializes in heart disease. They may prescribe treatment such as lifestyle changes and medication to lower cholesterol and blood pressure and reduce the risk of heart problems.

High blood sugar can damage blood vessels in the kidneys, which raises your risk of chronic kidney disease (CKD). You should get regular blood tests to check for CKD. If you develop advanced or complicated CKD, your doctor will refer you to a nephrologist. This doctor specializes in kidney disease and will prescribe treatments such as lifestyle changes, medication, and dialysis.

T2D raises the risk of anxiety and depression. A psychologist, clinical social worker, or licensed counselor can diagnose and treat mental health conditions with psychotherapy. A psychiatrist can prescribe medication if needed.