If you’re losing weight on Zepbound®, you’ve probably wondered: What happens if you stop? The answer has a lot to do with how the medication actually works. 

Zepbound® promotes weight loss by mimicking two natural hormones your body already produces: glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). GLP-1 keeps food in your stomach longer and lowers your appetite, affecting how much you eat. GIP limits cravings and helps cells burn energy. Together, they help people lose an average of 20% of their body weight. 

But once you hit that threshold, do you have to keep taking Zepbound® forever? What happens once you stop taking Zepbound®? 

In this article, we’ll explore the science behind the drug and explain what happens when you discontinue it.

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Discontinuing Zepbound®: What comes next?

Zepbound®’s effects wear off after you stop taking it, and research shows this can affect both weight and other health markers. Knowing what to expect can help you and your doctor plan the transition, rather than being caught off guard by it.

The Journal of the American Medical Association explored this in their 2024 SURMOUNT-4 study. They followed the weight loss outcomes of tirzepatide—Zepbound®’s active ingredient—in patients with obesity. A 2025 study interviewed SURMOUNT-4 participants. Many had discontinued treatment or switched to a placebo. 

A key finding is that appetite often returns once treatment stops, reversing the suppression Zepbound® provided. Of those who switched to a placebo and discussed appetite in their interviews, 86% reported that their appetite increased — a likely contributor to weight regain. 

Cardiometabolic markers can shift, too. A 2026 post-hoc analysis of SURMOUNT-4, published in JAMA Internal Medicine, looked at these outcomes. Here are examples of what researchers found: 

• Systolic blood pressure: This shows the force in your arteries when your heart beats, which can signal cardiovascular risk. It rose across all groups. 
• Non-HDL cholesterol: Total cholesterol in your body, minus the HDL (“good”) cholesterol, rose most notably among those who regained the most weight. 
• HbA1c: This test reflects average blood sugar levels over three months. It rose across all measured groups, indicating worsening blood sugar control.

This marks a reversal of the very cardiometabolic benefits Zepbound® can offer while you’re on treatment. 

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Weight regain: What the data shows

Regaining weight after discontinuing tirzepatide is common. In the 2026 post hoc analysis of SURMOUNT-4, 82.5% regained at least one quarter of the weight they lost on tirzepatide (254 of 308 participants). This regain occurred within one year after stopping. But the exact amount varied:

• Regained under 25%: 54 participants (17.5%)
• Regained 25% to 49%: 77 participants (25%)
• Regained 50% to 74%: 103 participants (33.4%)
• Regained 75% or more: 74 participants (24%)

Across groups, participants gained back an average of 15.1% of their body weight over the year. Approximately 9% regained more weight than before they began tirzepatide. A handful (around 4%) successfully maintained their weight loss progress. 

Here’s a side-by-side look at how cardiometabolic outcomes shifted across groups.

Can you stop Zepbound® "cold turkey"?

Yes. Patients commonly discontinue Zepbound® without tapering off, also known as cold turkey. 

But this is a decision to make with your doctor. They might determine that gradually lowering your dose is more beneficial. For example, researchers think that tapering patients off GLP-1 RA medications—Zepbound® being one—may limit weight regain. 

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How to maintain weight loss after Zepbound®

Keeping the weight off after Zepbound® is possible, but it’s a team effort. Don’t navigate this journey alone. Have a multidisciplinary team of clinicians in your corner who can support your transition from every angle. 

Here’s what they might discuss with you. 

Diet

Your appetite might change after discontinuing Zepbound®. This is a common and key contributor to weight regain. It’s important to have a plan. Improvising or relying on willpower can be a difficult, uphill battle. 

These tips can help:

• Work with a dietitian: Your body and goals are unique. A registered dietitian can build a tailored plan around your needs. They can continue to adjust your plan as your body and goals naturally evolve. 
• Adopt a muscle-preserving diet: Lean mass may account for 25% of total weight loss on Zepbound®. Regain may shift the balance toward fat accumulation. Muscle, which your diet can support, plays a key role in managing fat. 

Exercise

The body needs routine exercise. Your weight journey can benefit, but so can your overall health, including your heart, mood, and sleep. Start where you are and build from there. Consistency matters more than intensity, especially when you’re just starting out. 

Try these two types of training to get started:

• Resistance training: Aim for at least two days each week of resistance training, working all major muscle groups. Go for more days, if you can. 
• Cardiovascular training: According to the U.S. Department of Health and Human Services, staying active is one of the healthiest habits you can have. They recommend at least 150 minutes per week of moderate-intensity exercise or 75 minutes of vigorous exercise for general health upkeep. To prevent weight regain, you may need to work out up to 250 minutes per week. 

Sleep

Poor sleep may not only promote fat accumulation. It may also drive the breakdown of lean mass, which includes muscle. 

Small changes in your sleep habits can make a big difference:

• Keep a routine: Go to bed at the same time every night, and wake at the same time every morning. This helps support your circadian rhythm, which is associated with positive weight loss outcomes. 
• Prioritize sleep hygiene: This refers to the habits that support healthy sleep. Consider limiting caffeine intake (especially late in the day), avoiding large meals close to sleep, and limiting screen time at night. 

The earlier you adopt healthy practices, the better. Your care team may help you develop healthy habits while on Zepbound®, which carry over once treatment ends. 

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Care beyond the prescription

GLP-1 care plans shouldn’t stop at the prescription. That’s why Maven Clinic provides a whole-person approach.

Priya wrote about her experience: "I started on a GLP-1 somewhere else. The prescription showed up, and that was pretty much it. No real follow-up, no one thinking about how my hormones and metabolism were connected. I'm in my late 40s, and my body was changing in ways I didn't fully understand. When I switched to Maven, the difference was immediate. My clinician helped me figure out the full picture." 

At Maven Clinic, we deliver complete GLP-1 care with specialists covering 30-plus disciplines, who remain by your side each step of the way. We develop plans that support long-term, sustainable outcomes. 

Discover our approach to GLP-1 care.