BY HOLLY R. WYATT, MD, AND JAMES O. HILL, PHD

Not everyone feels great on GLP-1 medications.

Kendra, for example, lost over forty pounds and significantly improved her health, going off her diabetes and acid reflux medications. But she constantly feels tired, queasy, and unmotivated to exercise. Despite loving her new weight, Kendra is considering life without the medication because the side effects are interfering with her quality of life.

Emma and Alex, a married couple, each lost over thirty pounds and improved their health on the medication. But they’ve noticed they no longer enjoy food. Meals with friends, cooking together, and dining out, once favorite activities, now feel joyless because they’re rarely hungry and eat only a few bites. They love their new weight but miss their social life and are exploring how to maintain their weight without the medication.

Kendra, Emma, and Alex are far from alone. Stopping the medication is common. What comes next, keeping the weight off, is where most people find themselves without a clear strategy.

How GLP-1 Medications Work

GLP-1, or glucagon-like peptide-1, is a hormone produced in response to eating that plays a crucial role in metabolism and appetite regulation. It slows digestion, delays stomach emptying, and, perhaps most importantly, directly influences the brain, where its activation suppresses hunger, increases satiety, and curbs cravings. However, because natural GLP-1 disappears within minutes, its appetite-regulating effects don’t last long. This is where GLP-1-based medications change the game.

These new drugs are designed to mimic the effects of the natural GLP-1 hormone, like flipping a switch to turn on a light. What makes them effective is that they last much longer in the body than the natural hormone. Even when delivered through a once-a-week injection, GLP-1 medications help you feel full not just after meals but throughout the day. The result is a powerful amplification of the body’s natural satiety signals. For many people, this means feeling satisfied with less food, often something they haven’t experienced in years, if ever.

So, Why Lose the Medication?

Yenni lost twenty-five pounds on the medication, but she plans to start a family soon and knows she’ll need to stop during pregnancy. Nina lost thirty pounds and feels amazing at her new weight, but her insurance won’t cover the medication long term, and the out-of-pocket expense is too high for her to pay. Liam lost fifteen pounds in three months but couldn’t refill his prescription during a supply shortage. Even though the medication is available again, he’s curious whether he can maintain his progress without restarting it.

Whatever your reason, you’re not alone.

Many people assume they’ll be able to maintain their weight loss without medication, but the data tells a different story. Clinical trials show that most people (up to 80 percent) regain a substantial amount of the weight they lost, often about two-thirds, within a year of stopping GLP-1 medications. This weight regain may be even greater outside of clinical trials, where individuals typically don’t receive the same level of structured support, lifestyle counseling, or follow-up care.

Obesity is a chronic medical condition, and the new GLP-1 medications are not a cure. These medications don’t permanently alter your physiology or appetite. Once you stop taking them, the appetite control they provide will also stop. Your old physiology and drive to eat will return; you may feel hungrier, less full throughout the day, and more prone to food cravings and food noise.

To move forward, you need to break up with weight loss and start dating weight loss maintenance. Yes, they’re related, but they’re not the same.

Maintenance requires a different mindstate, new food and physical activity strategies, a deeper level of commitment, and a brand-new lifestyle. Ultimately, you’ll need to address all three key areas: food, physical activity, and your mind, but which you emphasize and when will depend on you.

Mistakes are part of the process, and perfection isn’t the goal, especially right out of the gate. Your plan will evolve as you learn what works best for you.

The Rules Change in Maintenance

Weight loss maintenance operates on a completely different principle than weight loss. During weight loss, success comes from creating a calorie deficit, also known as negative energy balance, by consuming fewer calories than your body burns.

The new weight loss medications like GLP-1 make this easier by suppressing appetite, allowing you to eat significantly less. This calorie deficit prompts your body to tap into its stored fat for energy, leading to weight loss.

However, in the maintenance stage, the focus shifts from achieving a calorie deficit to maintaining energy balance, where the calories you eat exactly match the calories your body burns. These two states require entirely different strategies and skills because they rely on distinct physiological processes. The methods that help create a calorie deficit during weight loss, like restricting calories, aren’t effective for maintaining energy balance over the long term.

As you lose weight, your body’s energy requirements decrease because a smaller body requires fewer calories to function, both at rest and during daily activities.

This means that if you want to maintain your new body weight, you won’t be able to eat as much as you did before weight loss, unless you change your energy requirements by moving more. Continuing to restrict caloric intake can work in the short term, but is rarely sustainable in the long term, because hunger will eventually overcome your willpower.

The answer isn’t more willpower; it’s a smarter strategy.

Physical Activity Is the MVP

During weight loss, cutting back on food is the go-to strategy for dropping pounds. In weight loss maintenance, the game changes. Physical activity, not diet, becomes the MVP, taking center stage in helping you sustain energy balance and maintain your results. Sure, managing your food intake still matters, but staying active now plays the leading role in keeping the weight off.

We like to think of it like a bus. During weight loss, food restriction is in the driver’s seat, steering the process, while physical activity sits in the passenger seat, just along for the ride. In maintenance, the roles flip. Physical activity takes the wheel, becoming the driving force, while food intake moves to a supporting role. If you don’t let physical activity take over as the driver, the bus won’t go anywhere.

We know that your food intake will increase when you stop the weight-loss medications like GLP-1, and this will lead to weight regain, unless you make a change. If you increase your physical activity enough, your higher energy expenditure will match your increased food intake and prevent weight regain.

Know this: While physical activity might not have been required to lose weight, it’s absolutely essential for keeping it off, and the research backs it up. For over thirty years, the National Weight Control Registry (NWCR) has studied more than ten thousand individuals who have successfully maintained an average weight loss of seventy pounds. A major key to their success has been consistently sustaining high levels of physical activity, on average, about one hour of planned physical activity per day.

The Commitment Is Lifelong

Food and activity are key players in both weight loss and weight loss maintenance, though they play different roles in each stage. But when it comes to long-term success, there’s another star player you can’t ignore: your mindstate.

Weight loss maintenance hinges on creating habits and routines that are sustainable, realistic, and—yes—even easy. Let’s face it, you can’t maintain your weight long-term if the process feels like a constant struggle. Healthy living does not have to be hard. Success in weight loss maintenance isn’t about willpower; it’s about creating a sustainable strategy that fits seamlessly into your life for years to come.

A focused mindstate is essential for staying on track when life throws its inevitable curveballs. Willpower and determination might get you through weight loss, but maintenance is a long game, and willpower doesn’t last forever.

Stress, unexpected events, holidays, or the simple ups and downs of daily life can all drain your willpower and easily derail your progress if you’re not mentally prepared to adapt. That’s where your mindstate makes all the difference.

It helps you manage stress, stay flexible, and respond to challenges without giving up on your long-term goals. In weight loss maintenance, your mindstate is the driving force that keeps you moving forward, no matter what life throws your way.

Inez has lost thirty-two pounds over the past eight months while taking weight loss medication. She describes her journey as a roller coaster, full of ups, downs, and unexpected turns. Work has been overwhelming, leaving little time for physical activity or meal prep.

Her husband, naturally slim, struggles to empathize with her challenges. A recent car breakdown made shopping for healthy foods difficult, and even buying new clothes, a moment she hoped would be joyful, was overshadowed by fear that her weight loss won’t last once the medication stops.

We call people like Inez Setback Cyclers. They often lose weight in bursts but struggle to maintain it, as life’s stressors and emotional challenges repeatedly knock them off course. When things get overwhelming, they may turn to food for comfort or fall off plan, and the cycle of losing and regaining weight begins again.

For people who resonate with this profile, the challenge isn’t just about appetite or metabolism; it’s about how they respond to life’s curveballs.

Success Means Living Beyond the Scale

This may be the biggest difference between weight loss and weight loss maintenance.

Weight loss maintenance isn’t just about staying at a specific number on the scale. During weight loss, the focus is often singular: reaching your weight goal, or “happy weight.”

But weight loss maintenance is about creating a life that feels meaningful, joyful, and sustainable, a life where your weight, health, and happiness are deeply connected.

It’s about expanding the idea of a “happy weight” into the bigger goal of a happy life. Weight loss maintenance is about aligning your goals with your core values, your identity, and the life you truly want to live.

What People Do Wrong

Weight loss and weight loss maintenance are fundamentally different. Using the same approach for maintenance as you did for loss is like mixing up the rules of two completely different sports; what works for one won’t necessarily win the game in the other.

Many people don’t realize there’s a difference between weight loss and weight loss maintenance, and as a result, they never officially transition into maintenance.

They do not know that weight loss is a temporary condition and weight loss maintenance is a separate, long-lasting phase that follows it. They may have been told inaccurately that whatever they did to lose the weight is also what they should plan to do for the rest of their life.

This group frequently says something like “I plan to keep eating what I am eating right now to lose the weight forever.”

But while they fully intend to do this, it rarely happens. The body is not designed to restrict calories forever. Eventually, they can’t eat the way they ate during weight loss, and without a strong alternative plan for weight loss maintenance, they regain the weight.

Staying in Weight Loss Too Long

Some people understand that weight loss and weight loss maintenance are different, but they make the mistake of staying in the weight loss phase for too long and miss the best opportunity to transition into maintenance. This is something we see far too often with people losing weight both with and without medications like GLP-1.

Here’s how it plays out. Someone loses weight successfully but wants to lose more, even though they’ve been in the weight loss phase for over six months and progress has stalled. Instead of transitioning into maintenance, they keep pushing, trying to force their body to lose more. Frustration builds as the scale refuses to budge. Eventually, they give up, revert to old habits, and regain the weight they worked so hard to lose.

Typically, we don’t recommend staying in the weight loss phase longer than three to six months. It is possible to stay in the weight loss phase longer while using medication if progress is steady. But once weight loss stalls and you’re thinking about stopping the medication, it’s critical to actively shift into weight loss maintenance.

Staying in weight loss mode when you’re no longer making progress isn’t just exhausting—it’s counterproductive. Your body adapts to the ongoing caloric restriction, making it harder to lose additional weight and easier to regain it. The better approach? Focus on successful maintenance first; then, after a stable period, consider returning to weight loss (and potentially weight loss medications like GLP-1) if you still want to lose more.

Your long-term weight loss maintenance game is yours alone. Strategies that work for one person may not be as effective for another. You might already excel at plant-forward eating or incorporating movement into your day, but need better strategies for overcoming emotional eating or managing life stressors. That is exactly what the work of maintenance is.

Where to Begin

You do not need to overhaul your entire life this week. Start with three things:

1. Commit to thirty minutes of movement per day—walking counts.
   
2. Identify one food habit from your weight loss phase that you can realistically sustain.
   
3. Notice your mindstate when a setback happens. Are you a Victim, a Victor, or working toward Voyager?

Awareness is the first step. The rest builds from there.

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Holly R. Wyatt, MD, is a physician, researcher, and expert in the art and science of weight loss maintenance. She’s spent more than twenty-five years helping people lose weight, keep it off, and live their best lives. Holly is a professor at the University of Alabama at Birmingham (UAB), where she teaches the next generation of health professionals and studies what it really takes to maintain long-term weight loss. She also co-hosts the Weight Loss and . . . podcast, where she shares practical, no-nonsense strategies for staying motivated, keeping the weight off, and, of course, living large.

When she’s not teaching, writing, or helping people live their best lives, Holly can usually be found trying to keep up with her merle pug, Bodie, who seems to have mastered the Voyager Mindstate—always curious, always exploring, and always finding the fun in every moment. Bodie is a daily reminder that the journey matters as much as the destination.

James O. Hill, PhD, is one of the world’s leading obesity researchers, with more than forty years of experience in the science of weight regulation. He has published more than six hundred scientific articles, co-founded the National Weight Control Registry, and is known for his groundbreaking work on weight loss maintenance. Jim has spent decades studying what it really takes to keep weight off for the long term, and he’s a passionate advocate for real-world, science-based solutions that actually work.

When he’s not in the lab or the classroom, Jim is an avid cyclist who has been known to tackle long rides with the same focus and determination he brings to his research. He’s also a fan of good data, a well-executed plan, and the kind of clarity that comes when you’re a few miles into a long climb.

Well Being Journal adapted the above excerpt from Losing the Weight Loss Meds by Holly R. Wyatt, MD, and James O. Hill, PhD. Copyright © 2025 by Holly R. Wyatt, MD, and James O. Hill, PhD. Printed with permission from BenBella Books, Inc.