How does Zepbound work for weight loss?

Zepbound (tirzepatide) is a once-weekly injectable prescription medication that can lead to an average weight loss of up to 20.9% in 72 weeks. The weight loss drug was approved by the US Food & Drug Administration (FDA) in 2023, and has been making headlines ever since, most recently as the first medication approved for sleep apnea at the end of 2024. But how does Zepbound work, exactly?

Read on as we answer that question and more, including who is Zepbound right for, how long do you have to take it, and what side effects you can expect.

“Zepbound works by mimicking the GLP-1 hormone in the body in order to regulate blood sugar, slow down digestion, and signal fullness to the brain. This helps to reduce appetite and make you feel full for longer after eating, which in turn supports weight loss,” says Paul Rosenberg, MD, a board-certified plastic surgeon who runs the New Jersey Gynecomastia Center, where he often treats patients for weight loss with GLP-1s prior to performing surgery. “It also improves insulin sensitivity, making it beneficial for people with insulin resistance or prediabetes.”

Zepbound is part of a larger category of drugs called GLP-1 receptor agonists, which treat obesity and overweight, type 2 diabetes, and cardiovascular disease (in conjunction with obesity or type 2 diabetes). GLP-1 stands for glucagon-like peptide-1, which is a gut hormone these drugs mimic. 

But Zepbound—and its sister medication, Mounjaro, which contains the same active ingredient (tirzepatide)--is unique among GLP-1 drugs. That’s because Zepbound is not just a GLP-1 receptor agonist, but a dual GIP/GLP-1 receptor agonist. Unlike Wegovy (semaglutide), Saxenda (liraglutide), and other GLP-1 drugs, Zepbound targets two receptors in the body, instead of just one. It works on both GLP-1 as well as GIP, which is short for glucose-dependent insulinotropic polypeptide. This may help explain why tirzepatide is more effective at both weight loss and blood sugar control than placebo when compared to the effects of single-receptor GLP-1s like Wegovy, Ozempic, or Saxenda versus placebo.

Both GIP and GLP-1 are gut hormones your body naturally produces. After you eat, these hormones direct your pancreas to release more insulin and tell your liver to slow down glucose production. This helps balance blood sugar levels. At the same time, these hormones slow down how quickly food moves through your stomach into the small intestine (a process known as gastric emptying) and send signals to your brain telling it you’re full. 

And, research shows their role in appetite regulation may go even further—by reducing cravings and quieting “food noise” (e.g. frequent, intrusive thoughts about food, such as when and what you’ll eat next).

So, as a recap, Zepbound works for weight loss by:

• Keeping food in your stomach longer, so you feel full sooner and longer

• Sending satiety signals to your brain that regulate your appetite, so you feel less hungry and consume fewer calories

• Quieting “food noise,” so you feel less focused on food

• Managing your insulin and glucose levels, so you avoid sugar spikes and crashes

Drugs like Zepbound treat weight loss from multiple angles, which is why you’ll often see them referred to as “second generation” weight loss medications, says Peminda K. Cabandugama, MD, a board-certified endocrinologist, Clinical Associate Professor of Medicine at the Cleveland Clinic Lerner College of Medicine of Case Western University, and Chair-Elect for The Obesity Society’s Clinical Practice Section. “These drugs work in two different ways to reduce how much we eat vs. earlier generation medications, which either cut down cravings or reduced food intake.” 

That multi-factored approach leads to impressive weight loss results, according to a 72-week clinical trial of people with obesity or overweight. Those who took Zepbound lost between 15-20.9% of their body weight, while the placebo group lost 3.1%. An extra analysis of the data from this study found that more than  one-third of participants on the highest 15-milligram dose of Zepbound lost at least 25% of their body weight. Note that this finding may be less reliable since it wasn’t the main focus of the research, but still supports Zepbound’s role as a powerful tool for weight loss.

In addition to the medication, participants also received counseling sessions to improve their diets (while eating 500 fewer calories a day) and increase their physical activity to at least 150 minutes weekly. Zepbound is meant to be used in combination with diet and exercise.

Zepbound has a half-life of 5 days. A drug’s half-life describes the length of time it takes to remove half of it from your body. Thanks to Zepbound’s multi-day half-life, you only have to inject the medication once a week.

However, because Zepbound has a decently long half-life, it also takes longer for it to flush out of your body fully. Once you stop taking Zepbound, it takes about 30 days for it to be completely gone, according to Eli Lilly, the maker of Zepbound. 

Zepbound starts working once you take it, but it will take about four weeks to reach a steady concentration in your bloodstream. People typically start to notice weight loss at this point, too, with those in clinical trials experiencing around 4% weight loss within the first month of taking Zepbound. The majority of weight loss occurs in the first nine months of taking Zepbound, although people may continue to lose weight if they keep taking the medication. 

While some weight loss can occur in the first four weeks of taking Zepbound, it typically takes longer for you to experience the full effects of the medication. In part, this is due to the drug’s gradual dosing schedule. 

Zepbound, along with other GLP-1 medications, follows a titration schedule, where you gradually increase your dosage of the medication over a period of weeks to months until you find a dose that’s effective and tolerable for you (e.g. you experience the therapeutic benefits and can manage the side effects). Once you reach that dose, you’ll stay at that dose. This is called your maintenance dose, and for Zepbound it’s either 5 mg, 10 mg, or 15 mg weekly.

Here is an overview of Zepbound dosages:

Zepbound is FDA-approved for weight loss and weight management in adults with:

• Obesity

• Overweight with a weight-related comorbidity such as type 2 diabetes, high blood pressure, high cholesterol, heart disease, or sleep apnea

In addition, as of December 20, 2024, the FDA approved Zepbound for a second purpose: to treat obstructive sleep apnea in adults with obesity.  

“A good candidate for Zepbound is typically an adult with a BMI of 30+ or someone with a BMI of 27+ who also has weight-related health issues like high blood pressure, type 2 diabetes, or sleep apnea,” says Dr. Rosenberg. “Good candidates are also those who are ready to commit to lifestyle changes, like a nutrient-rich, balanced diet and regular exercise, as Zepbound is most effective when used in combination with these healthy lifestyle changes.”

“Weight loss is not just about hitting a number, but also improving quality of life,” says Dr. Cabandugama. “Everyone [who is a candidate for Zepbound] has the same comorbidity, which is the reduced quality of life you have with obesity.”

Who should avoid Zepbound? 

Like most prescription drugs, Zepbound is not safe for everyone, and some people should not take it. “Anyone who has had, or has a family history of medullary thyroid cancer or multiple endocrine neoplasia syndrome type 2 is advised against taking Zepbound,” says Dr. Rosenberg. “If you react poorly to or have a known hypersensitivity to GLP-1 receptor agonists, you would also not be a good candidate for Zepbound or any other GLP-1 receptor agonists.”

Besides these contraindications, some people may be more likely to experience serious side effects on Zepbound, including those with:

• Severe gastrointestinal disease

• Kidney or gallbladder problems

• A history of diabetic retinopathy (a vision-related complication of type 2 diabetes)

People who are pregnant, trying to get pregnant, or planning to have surgery soon should tell their healthcare provider before starting Zepbound. Zepbound can also interact with insulin, insulin secretagogues, and oral contraceptives (i.e. birth control pills), so it’s important to share a full list of any medications you are taking with your doctor prior to starting Zepbound. They can advise you on how to adjust your dosage of these other medications or recommend another weight loss medication altogether.

“The most common side effects of Zepbound are nausea, vomiting, diarrhea, constipation, and GI discomfort,” says Dr. Rosenberg. “These side effects typically improve as your body adjusts to the medication.”

Here’s a list of the most common Zepbound side effects reported in clinical trials for weight loss: 

While rare, Zepbound can cause serious side effects. These include:

• Severe gastrointestinal reactions

• Acute kidney injury

• Acute gallbladder disease

• Acute pancreatitis

• Serious allergic reactions

• Hypoglycemia (low blood pressure)

• Diabetic retinopathy complications

• Depression and suicidal behavior or ideation

• Pulmonary aspiration during general anesthesia or deep sedation

How to manage Zepbound side effects 

Zepbound does have a long list of potential side effects, but the good news is that the most common ones like nausea and vomiting tend to lessen with time as your body gets used to the medication. If you’re experiencing gastrointestinal side effects on Zepbound, there are things you can do to manage them. 

“To manage side effects, it helps to eat smaller, more frequent meals and avoid large, high-fat, or greasy meals,” Dr. Rosenberg says. “Staying hydrated and eating bland, low-acid foods like crackers, rice, or bananas can also reduce nausea. If side effects persist or worsen, patients should talk with their healthcare provider about adjusting the dosage or the timing of the doses. If the side effects are really severe and can’t be tolerated, patients probably want to explore other more sustainable weight loss options.”

Other tips for managing Zepbound side effects include:

• Avoiding alcohol and carbonated beverages

• Eating slowly and stopping once you feel full

• Not lying down after you eat

• Ensuring you’re getting enough fiber in your diet

• Increasing your physical activity

• Asking your healthcare provider about anti-nausea medication, stool softeners, or probiotics

“Most people continue to take Zepbound as long as it’s effective and they can tolerate the side effects,” says Dr. Rosenberg. “If you stop taking Zepbound without incorporating significant lifestyle changes, appetite and weight gain often return.”

In one study of Zepbound, participants took the two highest maintenance doses for 36 weeks and lost 20.9% of their body weight, on average. Then, some participants were switched to a placebo while others kept taking Zepbound. Over the next year, those who switched to a placebo gained back 14% of their body weight, while those taking Zepbound continued to lose an additional 5.5%. 

“Weight is a set point,” says Dr. Cabandugama. “What we are doing [with these medications] is bringing that set point down. The weight can still go back up. The mindset we want people to think about with obesity is a chronic disease. If you have high blood pressure and your blood pressure is controlled, you don’t stop your medication, you keep taking it to keep it under control. If you think of obesity as a chronic disease, it’s the same thing: you want to manage it.”

• Zepbound works by mimicking two gut hormones that slow down gastric emptying, tell the brain you’re full, and manage blood sugar levels. 

• The active ingredient in Zepbound, tirzepatide, is unique among GLP-1 medications in that it targets both GLP-1 and GIP receptors. This makes it more effective at reducing appetite, controlling blood sugar, and managing body weight compared to single-receptor GLP-1 drugs like Wegovy and Saxenda. 

• Zepbound starts working as soon as you take it, but it can take about a month before you notice weight loss. By that point, people in clinical trials lost about 4% of their body weight.

• Zepbound may cause a number of side effects, many of which are digestive in nature and go away as your body gets used to the medication. with your full medical history and a list of any medications you are taking.

• While Zepbound produces significant weight loss, it works best when combined with a healthy diet and regular physical activity. Stopping Zepbound may lead to weight regain, especially if these lifestyle changes aren’t continued.

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Current version

January 25, 2025

Written by

Amelia Willson

Fact checked by

Patricia Weiser, PharmD

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About the medical reviewer

Patricia Weiser, PharmD

Patricia Weiser, PharmD, is a licensed pharmacist, health content writer, and medical reviewer with more than a decade of clinical experience in community and hospital pharmacy.