Zepbound vs. Wegovy: Which is best for weight loss?

Differences between Zepbound and Wegovy

There are several differences between how Zepbound and Wegovy work:

Zepbound

• Zepbound works by mimicking two natural hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). These help minimize hunger and regulate how the body processes sugar and fat. This dual action can lead to greater weight loss and improved blood sugar control.
• Zepbound targets both hunger and metabolism. The combination of GLP-1 and GIP means that it not only limits appetite but also improves how the body manages nutrients, giving it a potential edge for more significant weight loss.
• Zepbound has a flexible dosage that starts at 2.5 milligrams (mg) weekly. It can be increased to 15 mg, depending on individual needs and tolerance.

Wegovy

• Wegovy works by mimicking just one hormone, GLP-1. It limits your appetite and increases feelings of fullness after eating, which helps control calorie intake and leads to weight loss over time. While it doesn't target GIP like Zepbound, it's highly effective for weight management.
• Wegovy focuses primarily on hunger control. Its action on GLP-1 curbs appetite and promotes satiety, making it effective for those looking to manage their weight by eating less.
• Wegovy starts at 0.25 mg weekly and gradually increases to 2.4 mg. The gradual dose increase helps minimize side effects while achieving effective weight loss.

Effectiveness of Zepbound vs. Wegovy

Both Zepbound and Wegovy have been found to be effective for weight loss in obese and overweight individuals in conjunction with a reduced-calorie diet and a stepped-up exercise regimen. Here’s a breakdown of the effectiveness of each:

• Zepbound has shown greater weight loss in clinical trials. In a 72-week trial, participants using the highest dose of Zepbound (15 mg) lost an average of 21% of their body weight. Nearly 55% (54.9%) of participants lost 20% or more of their body weight.
• Wegovy led to significant weight loss but slightly less than Zepbound. In a 68-week trial, participants using Wegovy (2.4 mg) lost about 15% of their body weight.

These results tell us that Zepbound may be better for those seeking more aggressive weight loss, especially if previous treatments haven’t worked well.

The U.S. Food and Drug Administration (FDA) approved Wegovy in 2021 for weight loss among obese and overweight people. Then, in spring 2024, the FDA added another use, and now Wegovy is also used to reduce the threat of serious cardiovascular issues in those who are overweight or obese and have heart disease.

Wegovy remains a strong contender for moderate weight loss, especially in those with heart disease. Even though Wegovy’s weight loss results are slightly lower than Zepbound’s, it has proven cardiovascular benefits, making it a better fit for those with heart health concerns.

Both medications are administered as subcutaneous injections (beneath the skin) in the abdomen, thigh or upper arm. Since Zepbound and Wegovy are both injectable, they bypass the digestive system, leading to more consistent and effective results compared with oral weight loss medications.

Zepbound vs. Wegovy cost comparison

There is no doubt that weight loss injections can be expensive. Without insurance, both Zepbound and Wegovy are very costly:

• Zepbound generally costs $1,059.87 for a 30-day supply. This is the out-of-pocket price, but costs may be lower with insurance or manufacturer copay cards.
• Wegovy costs can be about $1,349.02 per month. However, eligible patients may use copay cards to lower costs, with some paying as little as $0, depending on their insurance coverage.

Wegovy’s added cardiovascular benefits might make it a better overall investment for people who need both weight loss and heart disease management, even if it’s more expensive.

Neither medication is typically covered by Medicare for weight loss, though Wegovy may be covered for its cardiovascular benefits for those at risk for cardiovascular disease, making insurance a major factor in choosing the most cost-effective option.

Manufacturer copay programs can also reduce costs for both medications. Both Zepbound and Wegovy offer copay assistance, which can significantly reduce monthly expenses for those with commercial insurance.

Also, a new program from LillyDirect allows consumers to get Zepbound in 2.5 mg or 5 mg doses for $399 and $549 per month directly.

Health care professional opinions on Zepbound vs. Wegovy

Dr. Anastassia Amaro, the medical director of Penn Metabolic Medicine, has pointed out that both Zepbound and Wegovy are highly effective in reducing appetite and promoting satiety, but Zepbound — with its dual action on both GLP-1 and GIP hormones —  may lead to slightly more significant weight loss compared with Wegovy.

For individuals considering these treatments and choosing between Zepbound and Wegovy, health care professionals advise evaluating personal health conditions, such as cardiovascular risks or blood sugar management needs.

Both medications require long-term use to maintain weight loss, and experts recommend incorporating lifestyle changes like resistance training and a balanced diet to optimize outcomes.

Zepbound vs. Wegovy side effects and safety

Common side effects for both Zepbound and Wegovy include gastrointestinal issues such as:

• Nausea
• Vomiting
• Diarrhea

These side effects are often seen early in treatment and may lessen as the body adjusts to the medication. According to Dr. Amaro, tirzepatide (Zepbound) tends to be better tolerated in terms of nausea, which might make it more appealing for patients sensitive to this side effect.

Gallbladder issues and rapid weight loss can pose risks for both medications as well, as rapid weight loss may increase the risk of gallbladder problems. Guidance for managing side effects includes dose adjustments and monitoring.

Health care professionals like Amaro recommend starting at a lower dose and gradually increasing it to help manage side effects. Patients are encouraged to keep an open line of communication with their doctors to manage any emerging symptoms.

Long-term safety monitoring is needed for both medications. While clinical trials have shown them to be effective and generally safe, ongoing observation for potential side effects like fatigue or rare complications like pancreatitis is recommended.

Bottom line

Overall, both Zepbound and Wegovy are good for people who are obese or overweight who are interested in losing weight. Zepbound appears more effective for significant weight loss, while Wegovy has added heart health benefits.

In terms of side effects, both drugs can cause nausea, vomiting and gastrointestinal issues, though Zepbound may be better tolerated in some cases.

Zepbound is generally more affordable than Wegovy, especially for those people without insurance. But Wegovy can be covered by Medicare and Medicaid if you also have cardiovascular issues.

Consulting with a health care professional is important to assess which medication is the best fit.