People with type 2 diabetes have a variety of options to manage the condition, including taking prescription drugs and making lifestyle changes. Glucagon-like peptide-1 receptor agonists (GLP-1 agonists) are one option.

In this article, Dr. Maria Prelipcean explains how GLP-1 agonists work, their benefits and risks, and some common side effects.

She also discusses the long-term risks for people who do not manage their type 2 diabetes effectively, along with some lifestyle changes that can make a difference.

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A doctor may prescribe GLP-1 agonists to help a person manage their type 2 diabetes.

GLP-1 agonists are a class of drugs that people use to manage type 2 diabetes.

GLP-1 is an incretin, which is one of the gut hormones involved in blood sugar control. GLP-1 agonists help reproduce or enhance the effects of this naturally occurring hormone.

GLP-1 agonists work in several ways, such as by:

  • stimulating meal-dependent insulin secretion by the pancreatic beta cells
  • decreasing the secretion of glucagon, a hormone that raises blood sugar
  • decreasing gastric emptying
  • decreasing appetite and reducing food intake by creating a sensation of stomach fullness

GLP-1 agonists may also have some direct effects on brain hunger centers. Since they decrease appetite, they may also help with weight loss.

Their main effect is to decrease spikes in blood sugar after eating. They have a smaller effect on fasting blood sugar levels.

They act mainly on insulin the body produces when a person eats a meal. This means that they are less likely to cause hypoglycemia if a person uses them in isolation, without other medications. However, people more commonly use GLP-1 agonists in combination with other medications for type 2 diabetes.

By themselves, they tend to reduce the glycohemoglobin by 0.5 to 1.2%. Glycohemoglobin is what an A1C test measures. Longer-acting types of GLP-1 agonist tend to reduce A1C levels slightly better.

GLP-1 agonists do not cause hypoglycemia. This is a significant advantage compared with other antidiabetic drugs.

They also do not cause weight gain. They may even contribute to weight loss, in the range of 1.5 to 3 kilograms. However, this amount varies depending on factors such as lifestyle or the use of other medications.

GLP-1 agonists may also have beneficial effects for heart and kidney health.

Researchers have investigated outcomes for people with type 2 diabetes who take GLP-1 agonists. They found that people who also had heart disease or heart disease risk factors had fewer cardiovascular complications than placebo groups when they took one of the following GLP-1 agonists:

Evidence suggests that all three of these drugs also reduce the progression of kidney disease in people at high cardiovascular risk.

GLP-1 agonists are either “short-acting” or “long-acting,” depending on their dosing schedule and duration of action.

A healthcare provider will recommend a specific medication based on factors such as patient preference, their experience with prior therapies, convenience, and insurance coverage. Currently, no comparative trials demonstrate how choice of medication impacts long-term outcomes.

Short-acting GLP-1 agonists have twice per day dosing. They tend to have a greater effect on after-meal blood sugars and gastric emptying, and a lesser effect on fasting glucose.

One example of a short-acting GLP-1 agonist is exenatide (Byetta).

Long-acting GLP-1 agonists have once-daily or once-weekly dosing. They have a more marked effect on fasting glucose. They may also be slightly more effective at reducing A1C results.

Some examples of long-acting GLP-1 agonists include:

  • liraglutide (Victoza), which people take once daily
  • semaglutide (Rybelsus), which people take once daily
  • dulaglutide (Trulicity), which people take once weekly
  • semaglutide (Ozempic), which people take once weekly
  • exenatide (Bydureon), which people take once weekly

The first medication that most people with type 2 diabetes use is metformin. Their doctor may also recommend making lifestyle changes.

However, type 2 diabetes is a progressive condition. Over time, most people will need to use additional therapies. People who experience severe side effects or other issues when they take metformin may also switch to GLP-1 agonists.

GLP-1 agonists may be a better choice when either weight loss or avoiding hypoglycemia is a priority. Healthcare providers may also recommend them for people with elevated postprandial blood sugars.

People with heart disease or heart disease risk factors are also good candidates for this therapy.

In most cases, injectable GLP-1 agonists can reduce blood sugar levels as much as daily insulin injections. People who are interested in GLP-1 agonists but who want to avoid injections could talk to their doctor about an oral form called semaglutide (Rybelsus) that recently became available.

Doctors primarily prescribe GLP-1 agonists in combination with other diabetes medications. The best combination of treatments for any person depends on many factors, including any other conditions they have, their own preferences, and cost concerns.

The most common side effects are gastrointestinal. Nausea, vomiting, and diarrhea can occur in many people. Nausea may improve with time and a lower dose. Also, it may occur less often with the weekly types of medication.

Some reports link acute pancreatitis with GLP-1 agonists, but there are not enough data to establish a clear causal relationship. If a healthcare provider suspects pancreatitis, a person should stop the drug and not restart it.

Researchers continue to investigate other possible adverse effects on the pancreas. For example, one group explored whether or not there could be a link between GLP-1 agonists and pancreatitis, as well as pancreatic cancer, but it did not find sufficient evidence of a link.

Some GLP-1 agonists may cause local skin reactions at the injection site. For example, people using exenatide (Bydureon, Byetta) have reported this side effect.

Hypoglycemia rarely occurs with GLP-1 agonists when a person uses them alone or alongside metformin. However, adding them to insulin-based therapies can increase the risk.

Diabetes carries an increased risk of complications involving the blood vessels. These are called microvascular and macrovascular complications.

Microvascular complications involve damage to the small blood vessels of the eyes, kidneys, and peripheral nerves. In turn, this leads to retinal damage, chronic kidney disease, and neuropathy.

The damage can be serious. For example, diabetes is one of the leading causes of blindness. It is also the most common cause of end stage kidney disease requiring dialysis.

Treatment makes a difference. A landmark study from 1998 showed that intensive diabetes therapy was associated with a 25% decrease in microvascular complications.

Diabetes also increases the risk of damage to large blood vessels (macrovascular disease) in the heart, brain, and legs. This type of damage increases the risk of heart attacks, strokes, peripheral vascular disease, infections, and amputations.

Managing diabetes effectively by keeping blood sugars within a healthy range makes a big difference in lowering the risk of these complications. It also helps address other risk factors for blood vessel problems.

To manage diabetes, healthcare providers will also encourage people to:

  • stop smoking
  • lose weight, if necessary
  • address high blood pressure, with lifestyle changes or medication
  • manage cholesterol levels, with lifestyle changes or medication

People who experience episodes of high blood sugar or severely low blood sugar can also experience serious complications. However, with proper monitoring and an individualized treatment plan, most people can prevent these complications or reduce how often they occur.

It is important for people to listen to their healthcare provider’s advice when it comes to their treatment plan.

People with a history of pancreatitis should not use GLP-1 agonists. Also, no one with a history of decreased kidney function should use the GLP-1 agonists Byetta or Bydureon.

Based on animal models, people should not use these medications if they have a personal or family history of certain health conditions, including medullary carcinoma of the thyroid or multiple endocrine neoplasia type 2.

Like any other diabetes medication, GLP-1 agonists should be part of a comprehensive individualized treatment plan. The goal of the treatment plan is to keep blood sugar levels in a healthy target range and manage overall health.

People with type 2 diabetes should make it a top priority to lower their risk of heart disease. This means following heart-healthy habits, along with managing blood pressure and cholesterol levels.

Depending on the individual, lifestyle changes may include:

  • modifying their diet
  • quitting smoking
  • losing 5–10% of their body weight, for those who have overweight or obesity
  • exercising for 150 minutes each week

Healthcare providers may also recommend that people manage cholesterol levels using statin medications.

Self-monitoring of blood sugar levels also improves blood sugar management. Individuals can use a fingerstick method or a continuous glucose monitor.

Seeing a dietitian may help with eating a more healthful diet. A dietitian can recommend an individualized nutrition plan that accounts for a person’s preferences and needs.

In general, when it comes to diet, people may improve their blood sugar management by reducing their intake of carbohydrates, saturated fats, and alcohol and using the diabetes plate method as basic guidance for meal planning.

Medication may also help with weight management in some cases.

When a person has very high blood sugar levels or other symptoms of type 2 diabetes, they need to use insulin. Making lifestyle changes as soon as possible, and sticking with them, may help people prevent the need for additional medication.

Dr. Maria Prelipcean is a physician specializing in endocrinology. She currently works at Southview Medical Group in Birmingham, AL, as an endocrinologist. In 1993, Dr. Prelipcean graduated from Carol Davila Medical School in Bucharest, Romania, with her degree in medicine. In 2016 and 2017, she was named one of the top doctors in Birmingham by B-Metro Magazine. In her spare time, Dr. Prelipcean enjoys reading, traveling, and spending time with her children.