Weight regain after weight loss medications: Zepbound, Wegovy, Saxenda, & Contrave

Do I need to take my weight loss medication forever? If I stop it, will I just regain all the weight? These are common questions patients ask, and ideally are addressed before someone even starts taking weight loss medication. Unfortunately, weight regain after stopping weight loss medication is a common occurrence, but the reason why is a lot more complicated than you might expect. We’ll break this down and highlight some strategies that may help reduce the total amount of weight regain if someone were to stop their medication.

What is weight regain after weight loss medications?

Weight regain is the increase in body weight that frequently occurs once a person stops taking a weight loss medication that initially helped that person lose weight. This can occur for a number of reasons. Some of the best studied mechanisms include changes in appetite hormones, a reduction in metabolism, and the loss of the appetite suppression from the medication. Two primary biological processes are at play when it comes to weight regain: hormonal and metabolic changes. For example, our fat cells produce the hormone leptin which works to lower appetite. When we lose weight, lower amounts of leptin are produced leading to an increase in appetite which can lead to weight regain. In addition, when individuals lose weight, their metabolism slows down as well which means we burn fewer calories at rest than when we were at a heavier weight making it easy to start to regain weight. This process is known as metabolic adaptation or adaptive thermogenesis.

Zepbound (tirzepatide) weight regain

Zepbound®, the medication most recently approved by the FDA to treat weight loss, has attracted a lot of interest from patients seeking an effective weight loss solution. This medication is a dual GLP-1/GIP receptor agonist medication that is used for chronic weight management in individuals living with obesity or with overweight and a weight-related medical condition (e.g. high blood pressure, high cholesterol, sleep apnea, etc.) in combination with a reduced calorie eating pattern and increased physical activity. Patients who took the highest dose of Zepbound (15 mg) were able to lose close to 21% of their starting body weight on average at 72 weeks. To date, this is the greatest average weight loss of any FDA-approved weight loss medication. Importantly, Zepbound is intended to be used long term for chronic weight management as it has been shown that those who stopped Zepbound after taking it for over 8 months experienced a 14% weight regain.

Wegovy (semaglutide) weight regain

Similar to Zepbound, Wegovy® is a GLP-1 receptor agonist medication that is FDA-approved for weight loss,* and after stopping the medication, weight regain commonly occurs. A study looked at patients who were treated with Wegovy for 20 weeks, and then half of them were switched to a placebo (something that has no therapeutic effect) while the others continued taking Wegovy. Those who switched to the placebo immediately started regaining weight, while those who stayed on Wegovy continued to lose. Another study looked at patients treated with Wegovy for over a year (68 weeks) and by that point they had lost an average of 17% of their starting weight. Afterwards, the medication was stopped and they were followed for an additional year (52 weeks). One year after stopping the medication, patients regained approximately two-thirds of the weight they had lost.

Saxenda (liraglutide) weight regain

Saxenda® is another GLP-1 receptor agonist medication that is FDA-approved for weight loss.* Similarly to the weight regain seen with other weight loss medications, a study demonstrated that patients who stopped taking liraglutide did regain weight one year after they stopped their medication. While the study did show that the rate of regain was slower in the group of patients who were exercising regularly during their treatment with liraglutide, exercise did not prevent the weight regain completely. This study underscores that exercise may help mitigate weight regain, but not fully prevent rebound weight gain from occurring.

Contrave (bupropion/naltrexone) weight regain

Contrave® is an FDA-approved weight loss medication that helps reduce appetite and curb cravings. It is a combination of bupropion (an antidepressant) and naltrexone (an opiate-receptor blocker) that was shown in clinical trials to lead to an average of at least 5% body weight loss after taking Contrave for 1 year. Over 15% of participants lost at least 10% of their body weight. While we do not have published research of the degree of weight regain that occurs upon discontinuing Contrave, we know that physiologic changes with weight loss promote weight regain and without the medication they are unopposed, and we have frequently seen weight regain after stopping from clinical experience.

How to prevent weight regain after stopping weight loss

Expert guidelines recommend continued use of weight loss medications for long-term weight management. However, there are circumstances where a person may no longer be able to continue their medication. For example, they may lose insurance coverage or they may need to take a different medication that negatively interacts with the weight loss medication they have been taking. In the case that you’re unable to continue taking your medication, here are some strategies to help minimize weight regain.  

Maintain healthy lifestyle changes

Weight loss medications are intended to be taken in combination with lifestyle changes such as increased physical activity and a low-calorie eating pattern. It is important to continue these healthy habits even after medication is stopped. One study showed that weight regain was slowed in patients who previously were on an established exercise routine and maintained physical activity after they stopped taking weight loss medications. Studies of participants in the National Weight Control Registry have also highlighted common practices among these long-term maintainers that have helped them keep the weight off.

Keep the right mindset

Behavior changes are a key component of successful, long-term weight loss success. A few things to remember if you are experiencing weight regain after stopping a weight loss medication include:

• While weight loss medications can certainly be helpful in achieving weight loss, they are only one tool in the toolbox, and certainly not the only tool.
• Have the right mindset when tackling weight loss. Make sure to stay motivated by asking yourself “why” you are going down this journey and continuing to reflect on how weight loss would benefit you. It is also beneficial to believe you are capable of taking actions that lead to a desired outcome. If you’ve lost weight in the past, it means you can do it again! Setting realistic goals and an achievable game plan will help with long term success, as well as being kind to yourself throughout the journey.
• Engage in healthy eating habits and consistent physical activity as well as incorporate new behavior change in conjunction with weight loss medications. As we discussed above, there are physiologic changes in the body that happen after weight loss that promote regain. These are not something you have willful control over and therefore weight regain has nothing to do with a lack of willpower.
• Weight regain does not mean you will never lose weight again.

Get support from your medical team at Form Health

At Form Health, patients receive personalized, science-based weight management support.  Patients meet regularly with their expert physician and frequently with their Registered Dietitian. Our physicians are experienced in working with patients who have had to stop their weight loss medications and will work with you to understand your unique challenges and develop a personalized treatment plan to help you lose weight and keep it off long term.

Achieving your weight loss goals with Form Health

In summary, clinical studies show that weight regain can occur after stopping weight loss medications. However, this does not mean that every patient regains weight nor does it mean you cannot reach your health goals. The clinical team at Form Health consists of expert medical clinicians and Registered Dietitians who support patients every step of the way in a manner that is sustainable and effective. They also have experience working with patients who have found themselves no longer being able to take medications that were previously very helpful, and can provide expert guidance to promote sustained weight loss without medications. Take the quiz or send a message to Form Health today to learn more.

‍*FDA-approved for chronic weight management in individuals living with obesity or with overweight and a weight-related medical condition (e.g. high blood pressure, high cholesterol, sleep apnea etc.) and used in combination with a reduced calorie eating pattern and increased physical activity.