How does Ozempic work? Understanding GLP-1s for diabetes, weight loss, and beyond

Ozempic and other GLP-1 receptor agonists have gained attention for their role in treating type 2 diabetes and promoting weight loss. These medications mimic a hormone that helps regulate blood sugar and appetite. While their benefits are clear, they also come with potential risks and side effects.

How do GLP-1 drugs like Ozempic work?

GLP-1 (glucagon-like peptide-1) receptor agonists are a class of medications that work by mimicking the natural GLP-1 hormone. This hormone is released by the gut in response to eating and has several effects that help regulate blood sugar levels, hunger, and slow digestion. Tirzepatide is a related drug that mimics GLP-1 as well as a hormone called a glucose-dependent insulinotropic polypeptide (GIP).

Most GLP-1 drugs are administered by injection into the abdomen, thigh, or upper arm.

How do GLP-1s help manage diabetes?

For people with type 2 diabetes, controlling blood sugar levels is essential to preventing complications like nerve damage, kidney disease, and heart problems. GLP-1 receptor agonists like semaglutide (Ozempic), liraglutide (Victoza), and tirzepatide (Mounjaro) help by increasing insulin secretion in response to meals, thereby lowering blood sugar levels. They also lower levels of glucagon, a hormone that raises blood sugar.

GLP-1 drugs lower blood sugar only when it's high, unlike insulin, which works regardless of glucose levels. This glucose-dependent action reduces the risk of dangerously low blood sugar (hypoglycemia), making them a safer option compared to some other diabetes treatments

GLP-1 receptor agonists also reduce the likelihood of developing heart-related problems such as heart attacks or strokes. This is an important consideration because diabetes increases heart disease risk.

How do GLP-1s support weight loss?

One of the reasons GLP-1 receptor agonists have gained so much attention is their ability to help with weight loss. These medications slow down stomach emptying, keeping you feeling full longer. They also send signals to the brain that increase feelings of fullness, leading to reduced food intake.

GLP-1s are typically prescribed at a higher dose for obesity than for diabetes. Liraglutide (Saxenda), semaglutide (Wegovy), and tirzepatide (Zepbound) are all FDA-approved for weight loss.

In some studies, participants using GLP-1s have lost an average of 10% to 15% of their body weight over a year. The most effective GLP-1 medications can lead to weight loss of over 20% of body weight. This level of weight loss is significant because even a 5% to 10% reduction in body weight can improve metabolic health, lower blood pressure, and decrease the risk of conditions like fatty liver disease and obstructive sleep apnea.

Side effects you may experience with GLP-1s

Like any medication, GLP-1 receptor agonists may cause side effects in some people. These side effects often improve as the body adjusts to the medication. To minimize them, doctors typically start with a low dose and gradually increase it over time. Some of the most common GLP-1 side effects include:

• nausea
• vomiting
• diarrhea
• constipation
• abdominal discomfort.

Other less common but possible side effects include headaches, increased heart rate, dizziness, and fatigue. Some individuals may also experience mild injection site reactions such as redness or itching.

Dr. Chika Anekwe, Obesity Medicine Clinical Director at Massachusetts General Hospital Weight Center and instructor at Harvard Medical School, points out that a common misconception is that everyone experiences major side effects. "While gastrointestinal side effects like nausea and constipation are common, they are usually temporary and manageable," she notes.

Possible risks of GLP-1s

While GLP-1 drugs are generally considered safe, they do come with potential risks. Persistent nausea or vomiting can lead to dehydration, kidney problems, or malnutrition in some cases. People with serious gastrointestinal conditions, like gastroparesis or uncontrolled inflammatory bowel disease, should not take GLP-1 medications. And these medications are not considered safe for use during pregnancy or breastfeeding.

Other health risks include:

• Pancreatitis: Some studies suggest a possible link between GLP-1s and inflammation of the pancreas, though the risk appears to be low.
• Gallbladder problems: Some people develop gallstones or gallbladder inflammation while taking GLP-1s. (Gallstones can also result from rapid weight loss in the absence of GLP-1 medication.)
• Thyroid tumors: Animal studies have raised concerns about a potential link between GLP-1s and thyroid tumors, but ongoing surveillance has not shown that this applies to humans.
• Muscle loss: Some reports suggest that rapid weight loss from GLP-1s may lead to a decrease in muscle mass. (Weight loss even without GLP-1 medication results in some loss of muscle.) This is of particular concern for older adults, who may be at a higher risk for frailty and falls.

If you are taking or considering a GLP-1, discuss these risks with your doctor. There may be things you can do to mitigate some of these risks. For example, your doctor may advise you to increase your protein intake to reduce the risk of muscle loss.

Finally, beware of compounded GLP-1 drugs, which became popular during a GLP-1 drug shortage starting in 2022. The FDA has issued warnings about compounded GLP-1 drugs because of reports of harmful side effects. The FDA does not check compounded drugs for safety, effectiveness, or quality.

Potential benefits of GLP-1s under investigation

Beyond diabetes and weight loss, researchers are exploring other potential benefits of GLP-1 drugs. Major areas of exploration include:

• Heart health. Heart health remains a major area of interest. Research has suggested GLP-1s may reduce the risk of heart attack and stroke in people with diabetes or obesity.
• Brain health. Research is ongoing to determine whether these drugs could help protect against neurodegenerative diseases like Alzheimer's. Dr. Anekwe highlights that "some research shows GLP-1s may slow cognitive decline and have a role in neuroprotection."
• Addiction treatment. Some early studies suggest GLP-1 drugs may help reduce cravings for substances like alcohol and nicotine.
• Liver disease.Metabolic associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), and metabolic-associated steatohepatitis (MASH), formerly known as non-alcoholic steatohepatitis (NASH), are conditions linked to obesity and insulin resistance. GLP-1 drugs may help reduce liver fat and inflammation, potentially slowing disease progression.
• Sleep apnea. In December 2024, the FDA approved tirzepatide (Zepbound) to treat moderate to severe obstructive sleep apnea in adults with obesity.

"The most notable benefits of GLP-1 receptor agonists for patients with diabetes or obesity are their ability to promote significant weight loss, reduction in appetite, and improvement in blood sugar control," says Dr. Anekwe. She continues, "The cardiovascular protection and other emerging benefits, such as improvements in outcomes related to metabolic-associated liver disease and obstructive sleep apnea, are additional benefits of these medications."