Glucagon-like peptide-1 (GLP-1) agonists are injectable weight loss drugs that help people feel fuller and eat less food, leading to weight loss. The drugs also boast other long-term benefits, such as protection against cardiovascular disease.
GLP-1 receptor agonists, sometimes simply called GLP-1s, were originally developed to manage the blood sugar levels of people with type 2 diabetes. Researchers later learned that GLP-1 drugs could also cause dramatic weight loss in people who do not have diabetes.
The U.S. Food and Drug Administration (FDA) has approved three GLP-1 drugs for weight loss in people with overweight or obesity:
semaglutide (Wegovy)
tirzepatide (Zepound)
liraglutide (Saxenda)
Tirzepatide, though generally grouped with semaglutide and other GLP-1 drugs, is technically a GIP/GLP-1 drug, because it mimics both GLP-1 and GIP, a second digestive hormone.
All three GLP-1s are injectable medications that come in prefilled pens. Once per week, users attach a needle to their pen, prick themselves in the torso or another fleshy area, and press a button on the pen to administer their medication.
Doctors start their patients on lower “starter” doses and work their way up — it can take months to work up to a full-strength dosage.
Each of these drugs is also marketed under a different name for the treatment of diabetes: semaglutide (Ozempic), tirzepatide (Mounjaro), and liraglutide (Victoza). This may cause some confusion: Though Ozempic and Wegovy, for example, come in different packages and in different doses, they are in fact the same drug.
GLP-1 drugs mimic a hormone named GLP-1 that our bodies naturally produce during and after meals. This hormone plays several important roles in regulating our hunger and metabolic health. GLP-1:
Signals a feeling of being full
Slows down digestion
Regulates the release of insulin from the pancreas
GLP-1 drugs also act directly on the brain. Many users report that they suddenly have fewer intrusive thoughts about food, or food noise. GLP-1s may also help people naturally crave healthier food, by reducing preference for fatty, high-calorie foods.
In a nutshell, GLP-1 drugs allow people to eat less without feeling hungrier than normal. Some users can happily eat as much as they want, and will still lose a substantial amount of weight.
Wegovy, Zepbound, and Saxenda are all approved as weight loss medications for the following people with a demonstrated medical need to lose weight.
Adults with a BMI of 27 or greater who also have one weight-related condition, such as type 2 diabetes, high blood pressure, or high cholesterol
Wegovy and Saxenda are also approved for the treatment of children aged 12 and older; the precise BMI cutoffs for children differ by age.
Only your healthcare team can decide which of these drugs, if any, will work best for you.
Not everybody responds equally well to these treatments, and it’s impossible to predict how effective any specific weight loss medication will be for you. The results of major clinical trials suggest how much weight the average user may expect to lose.
On the maximum dose of Wegovy (2.4 milligrams [mg]), clinical trial participants lost an average of about 15 percent of their body weight after more than a year of taking semaglutide — with an average starting weight of 232 pounds (lb), that meant a loss of about 34 lb.
People may lose even more weight with Zepbound. In its major clinical trial, volunteers on the maximum dose (15 mg) lost about 21 percent of their body weight — from an average starting weight of 231 lb, they lost about 52 lb.
But some people will not see these results. About 15 percent of Wegovy users and 9 percent of Zepbound users lost less than 5 percent of their body weight. Additionally, a minority of users will find it necessary to discontinue the drug because they cannot tolerate the side effects. In clinical trials, about 6 percent of Wegovy and Zepbound users dropped out due to side effects, mostly gastrointestinal issues such as vomiting and nausea.
Saxenda also delivers substantial results. When study participants took 3.0 mg of Saxenda weekly for 56 weeks, they lost an average of about 8 percent of their body weight — about 18 lb from their average starting weight of 234 lb.
GLP-1 weight loss also seems to do an especially good job of targeting the loss of fat in the abdomen, sometimes called visceral fat. This fat, which squeezes around the vital organs, is considered much more dangerous than the fat found elsewhere on the body.
It’s important to emphasize that GLP-1 weight loss drugs are meant to be used in tandem with regular exercise and a healthy diet. The weight loss reported in the above studies all occurred in volunteers who were also asked to maintain healthy eating and exercise habits.
GLP-1s have health benefits that extend beyond weight loss.
Heart Health Protection
When people who are overweight use semaglutide and tirzepatide, they tend to experience broad cardiovascular and metabolic health improvements, including:
Lower blood pressure
Lower total cholesterol
Better liver health
Lower blood sugar and reduced diabetes risk
Lower risk of kidney disease
Long-term cardiovascular outcome trials show that semaglutide can significantly reduce the risk of early death from heart attack, stroke, or heart disease. Semaglutide can now be prescribed specifically for cardiovascular protection in people who are overweight or have obesity.
Tirzepatide is a newer drug and has not yet been fully studied in long-term cardiovascular health trials. But some researchers expect that it will prove to have a similarly powerful protective effect on heart health.
Secondary Benefits
GLP-1 drugs also appear to have some extra benefits.
Tirzepatide is a potent treatment for obstructive sleep apnea. It is possible that semaglutide also improves sleep apnea, but its manufacturer has not organized any experiments to investigate this effect.
GLP-1 drugs reduce inflammation throughout the body.
GLP-1 drugs also seem to have anti-addictive properties — some users report that they have fewer cravings for alcohol or have become less likely to engage in other addictive behaviors, such as gambling, shopping, or nail-biting. Researchers are now studying semaglutide and similar drugs for their anti-addiction effects.
Preliminary studies have suggested that GLP-1 drugs might protect against or treat dementia and Alzheimer’s disease.
GLP-1 drugs are associated with a wide variety of side effects.
Common Side Effects
Gastrointestinal distress is the most common side effect reported by people who take GLP-1s, and is experienced by a high percentage of users. Nausea and diarrhea are most common, followed by constipation, vomiting, and abdominal pain.
In the majority of people in clinical trials, these side effects have been mild or moderate. Gastrointestinal issues are usually strongest in first-time users, or when people step up to a larger dosage, but they usually dissipate over time. A small number of users may experience gastrointestinal effects so severe that they need to stop taking the medication.
Rare, More Serious Side Effects
Other side effects are much more rare, but potentially serious. GLP-1 agonists can cause inflammation of the pancreas, called pancreatitis, bowel obstruction, and gastroparesis (paralysis of the stomach). In people who are allergic or hypersensitive to GLP-1s, the drug can cause anaphylaxis, a dangerous reaction that can involve the rapid onset of hives, swelling, and even loss of consciousness.
GLP-1 drugs can also create a risk of hypoglycemia, or dangerously low blood sugar, in people who use certain type 2 diabetes drugs, chiefly insulin and sulfonylureas.
Anecdotal Side Effects
There has also been plenty of media buzz about anecdotal side effects with names like “Ozempic face” and “Ozempic butt.”
These cosmetic side effects aren’t unhealthy, and aren’t directly caused by GLP-1s. Instead, they are caused by rapid significant weight loss.
Weight loss can make parts of your body look different. While your belly may slim down, so might your buttocks and face. In some people, weight loss can lead to looser or sagging skin. Weight loss can also cause hair loss, and may be responsible for other rarely reported side effects, such as tiredness.
GLP-1 drugs are powerful medications that may not be appropriate for everybody.
GLP-1s may be risky for older adults. Significant weight loss isn’t always a benefit for older adults, especially if it means the loss of bone and muscle mass, which are critical for good physical health. It is possible to reduce the risks by eating enough protein and engaging in strength-building exercises, such as weight lifting.
People who should not use GLP-1s include:
Pregnant people
People with a personal or family history of medullary thyroid cancer
People with multiple endocrine neoplasia syndrome type 2, a rare condition that affects the endocrine glands
People who are hypersensitive to GLP-1 agonist drugs
Experts say that you need to keep taking GLP-1 drugs if you want to continue to enjoy the benefits. When you stop taking a GLP-1 agonist, you will probably regain some or all of the weight you lost. Your hunger and “food noise” may return to previous levels.
One trial found that people who stopped taking 2.4 mg weekly doses of semaglutide regained about two-thirds of the weight they had lost. But the people in this study also stopped their exercise and dieting regimens they were on while taking the drug.
Healthy diet and exercise habits can also help maximize the benefits of GLP-1 drugs. Nutrition is still crucial, as getting the right amount of protein, fiber, nutrients, and hydration is more difficult when you’ve drastically cut your food intake. And exercising can enhance the health benefits and prevent some of the bone density loss that usually occurs during weight loss.
If you establish healthy diet and exercise habits while using a GLP-1 it will be easier to maintain some weight loss if you have to stop taking the medication.
Public insurance coverage for GLP-1 drugs obesity treatments is spotty in the United States.
Only a minority of state Medicaid boards have chosen to cover GLP-1 drugs when prescribed as an obesity treatment, coverage in ACA Marketplace plans is limited. Medicare does not cover obesity treatments, though it is possible to have Wegovy approved and reimbursed if it has been prescribed for cardiovascular health.
Private insurers vary widely in their coverage. Most large employers do not offer GLP-1 coverage for weight loss. Some insurers, faced with staggering costs due to the huge number of claims for GLP-1 drugs, have tightened or revoked their coverage.
Many users are left to pay for GLP-1 weight loss medications, which can cost more than $1,000 per month, out of pocket.
The high price of GLP-1s has created a market for less-expensive compounded versions of the drugs. These off-brand semaglutide and tirzepatide equivalents are mixed in a private compounding pharmacy and are not subjected to rigorous FDA testing. Many doctors endorse and prescribe compounded GLP-1 weight loss drugs, but others warn explicitly against their use. It is unclear how long compounded GLP-1 drugs will remain available: GLP-1 manufacturers are arguing to restrict the sale of compounded weight loss drugs, and the compounding pharmacies are pushing back.
GLP-1 agonists are not the only option for weight loss.
It may go without saying, but the old-fashioned way — diet and exercise — remains a preferred weight loss method. Indeed many doctors require people to try diet and exercise alone before trying GLP-1s. Different eating patterns and exercise regimens work for different people, and it’s best to work with a doctor or dietitian if you can. Low-carb and Mediterranean diets are both popular and research-backed ways of eating that can help people lose excess fat. A combination of cardio exercises and strength training is often the best exercise strategy for weight loss.
If you cannot access or afford newer GLP-1 medications, a generation of older weight loss drugs is still available. Though these drugs are generally less effective than newer alternatives, they can work for many people:
Orlistat (Alli, Xenical) reduces the amount of fats absorbed by the intestines.
Phentermine-topiramate (Qsymia) suppresses appetite and helps people eat less.
Bupropion-naltrexone (Contrave) reduces hunger signals in the brain.
Weight loss surgery, or bariatric surgery, is also an option for some people with a need to lose weight. The benefits are comparable or superior to the benefits of GLP-1 drugs, including dramatic weight loss and secondary long-term health benefits, such as improved blood sugar levels. Weight loss surgery may seem intense and expensive, but it is often covered by insurers, and the out-of-pocket cost could be far less than years of GLP-1 therapy.
GLP-1 drugs, especially semaglutide and tirzepatide, can provide weight loss unmatched by previous weight loss drugs.
These medications, which help users eat less food by reducing hunger, have additional health benefits, such as improved blood pressure and cholesterol.
GLP-1 drugs do not work for everyone, and a minority of users cannot tolerate their common gastrointestinal side effects.
Diet and exercise remain important even when losing weight with a GLP-1, in order to maximize the benefits and build healthier habits to help with weight loss maintenance.
