How GLP-1 Drugs Work: The Science Behind Ozempic, Wegovy, and More
Published on July 29, 2026
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How GLP-1s Work
GLP-1 drugs support weight loss, lower blood sugar, and are being studied for their potential beyond type 2 diabetes and obesity. Deena Adimoolam, MD, an endocrinologist at Summit Health in New Jersey, breaks down how GLP-1s work in the body.
GLP-1 drugs such as Ozempic and Wegovy are everywhere, but most people don’t know what they do or how they work.
GLP-1 drugs were originally prescribed to people with type 2 diabetes or obesity, but they’ve been shown to have other uses as well. They aid in weight loss by suppressing hunger, while also lowering blood sugar and blood pressure, by mimicking the GLP-1 hormone that occurs naturally within the body.
But what exactly is happening in the body to create these benefits? Read on to learn five ways that the drugs work.
They Tell Your Pancreas to Release Insulin — but Only When Needed
Following a meal, the body releases GLP-1. This naturally occurring hormone tells the pancreas to release insulin — a process known as the incretin effect — to help lower blood sugar levels in response to food. GLP-1 drugs enhance this response, which can be particularly helpful among people with type 2 diabetes, who may have a reduced natural GLP-1 response.
Other diabetes drugs release insulin regardless of glucose levels, which could lead to high blood sugar after meals and low blood sugar between meals. GLP-1s, on the other hand, release insulin only when glucose levels are elevated. “Since they depend on the presence of glucose, they’re much less likely to cause low blood sugar on their own,” says Peter Balazs, MD, with Hormone and Weight Loss Doctors of NJ in New Jersey.
They Put the Brakes on Glucagon (Your ‘Raise Blood Sugar’ Hormone)
The role of glucagon, a hormone produced by the pancreas, is to make sure blood sugar levels don’t drop too low. Think of it as the opposite of insulin, a hormone that lowers blood sugar levels. Glucagon helps raise blood sugar by telling the liver to transform glucagon into its usable form and then release it into the bloodstream.
GLP-1 drugs suppress the release of glucagon and block the liver from receiving the signal to release more sugar. This can contribute to a more controlled blood sugar response after a meal, says Vallari Kothari, MD, an endocrinologist at Montefiore Einstein in New York City.
They Slow Down Digestion, so Sugar Enters the Bloodstream Gradually
GLP-1 drugs delay gastric emptying, or the rate at which food leaves the stomach. By slowing down this process, the stomach holds food longer than it otherwise would, leading to extended feelings of fullness. GLP-1s have this effect because they prevent muscles in the gut from contracting and also activate the vagus nerve, which is part of the nervous system that plays a role in gastrointestinal tract activity.
The delayed gastric emptying also limits blood sugar spikes after meals, since the food is released gradually instead of all at once. “Think of your stomach as a funnel — when food empties quickly, glucose floods into your bloodstream all at once, creating a big spike in blood sugar,” Dr. Kothari says. “GLP-1 medications narrow that funnel, so glucose trickles in more gradually, producing a gentler, lower rise in blood sugar.”
This is especially helpful for people with type 2 diabetes because their bodies cannot handle glucose spikes the way a person without diabetes can, Kothari says.
They Signal to Your Brain That You’re Full — Faster and Longer
GLP-1s contribute to weight loss by telling the brain that the body is “full” via a communication network between the stomach and the brain.
When GLP-1 is released by the gut, it travels to the hypothalamus, an area of the brain that plays a role in feelings of hunger and fullness. GLP-1 binds to its receptors in the hypothalamus and triggers neurons that promote fullness and minimizes those that promote hunger. GLP-1 drugs are stronger and longer-lasting than the body’s natural GLP-1 hormone, says Janelle Duah, MD, associate medical director at Maven Clinic, a virtual clinic of women’s and family health, based in New Haven, Connecticut.
They Reduce Food Cravings and ‘Food Noise’
GLP-1 drugs also reduce food noise, or intrusive thoughts about food that may drive overeating or emotional eating. What’s more, GLP-1 drugs may reduce the cravings for sweets and other unhealthy foods and change one’s food preferences altogether.
“Many of my patients tell me that one of the biggest changes isn’t the weight loss — it’s that they’re no longer constantly thinking about food,” Dr. Balazs says. “The mental chatter, cravings, and preoccupation with eating often become much quieter, which can feel incredibly freeing.”
Emerging research has also shown that GLP-1 drugs can reduce the desire to eat for pleasure. One recent animal study found small-molecule versions of the drugs altered the reward circuit within the brain’s central amygdala region. Researchers are now wondering if this could apply to things other than food and whether GLP-1s could reduce cravings associated with substance abuse.
Some GLP-1 Drugs Target More Than One Hormone
GLP-1 drugs can be single, dual, or triple agonists, depending on how many hormones they target. Single agonists target one (GLP-1); dual agonists (such as tirzepatide) target two (GLP-1 and gastric inhibitory polypeptide, or GIP); and triple agonist drugs (such as retatrutide) target three (GLP-1, GIP, and glucagon).
GIP
Tirzepatide (brand name Zepbound for weight management and Mounjaro for type 2 diabetes) is an injectable medication that activates GLP-1 and GIP receptors.
It has been shown to lead to better blood sugar control, improved hemoglobin levels, and greater weight loss in people with type 2 diabetes, compared with drugs that target GLP-1 alone. “Researchers believe this happens because GLP-1 and GIP work in complementary ways,” Dr. Duah says. “Both help reduce appetite, but they act on different pathways in the brain.”
GIP and Glucagon
Retatrutide, an experimental triple agonist drug that targets GIP, GLP-1, and glucagon, is currently being studied and has not yet been approved by the U.S. Food and Drug Administration, Duah says.
But preliminary research shows that it may lead to more weight loss than single and dual agonist drugs. A recent trial from the drugmaker Eli Lilly involving adults with overweight or obesity plus one weight-related comorbidity found that retatrutide led to an average weight loss of 28 percent body weight after 80 weeks on the highest dose. By comparison, taking the GLP-1 semaglutide for 68 weeks resulted in an average weight loss of 16 percent, in an earlier study.
Retatrutide also has been shown to reduce A1C levels (which measures average blood sugar over the past three months) in people with type 2 diabetes.
Why GLP-1 Drugs Cause Certain Side Effects
Common side effects of GLP-1s include nausea, vomiting, and diarrhea. These are due to the delayed gastric emptying, the same mechanisms that make them effective for weight loss and blood sugar control, Duah says.
“These medications also interact with areas of the brain involved in appetite regulation and nausea,” Duah says. “In some people, that signaling can temporarily trigger nausea, particularly during the first few weeks of treatment.” Diarrhea and constipation can also happen because GLP-1 can affect bowel movements, she adds.
Rare but serious side effects include pancreatitis, gastroparesis, bowel obstruction, gallstone attacks, and bile duct blockage. These rare complications are also primarily due to the drug slowing stomach emptying, Kothari says.
Tirzepatide has been shown to have a higher risk of side effects like nausea and diarrhea, compared with other options, according to a review involving more than 27,000 participants.
“Side effects are most common during the first several weeks of treatment and after dose increases, and they often improve as the body adapts,” Duah says. That’s why the drugs are typically started at a low dose and increased over several months, Kothari says.
Side effects tend to be the same whether you’re taking an oral or injectable form of GLP-1s, Kothari says.
EDITORIAL SOURCES
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Adam Gilden, MD, MSCE, is an associate director of the Obesity Medicine Fellowship at University of Colorado School of Medicine and associate director of the Colorado University Me...
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