Semaglutide and Weight Regain: A Comprehensive Guide to Preventing Weight Recurrence After GLP-1 Therapy

Semaglutide has helped many people successfully lose weight, but once the weight is gone, many discover a difficult truth: weight regain is common. In one study, participants regained up to two-thirds of the lost weight within one year of stopping semaglutide. In fact, keeping the weight off is sometimes as hard as initially reaching your weight goal.

But hard doesn’t mean impossible. With the right weight maintenance strategies and an understanding of why weight regain happens in the first place, it is possible to stop the pounds from creeping back.

The Biology of Weight Regain: Why Your Body Fights Back

Weight regain is the most common outcome of stopping semaglutide. There are a few biological reasons acting in favor of gaining weight after discontinuing this medication, including hormonal and metabolic factors.

The Hormonal Battle: Ghrelin, Leptin, and GLP-1

Semaglutide mimics GLP-1, a hormone that naturally occurs in the body. GLP-1 triggers receptors in the digestive system and brain that reduce hunger cues and slow gastric emptying, which leads to feeling full for longer. Once you stop semaglutide, these two effects diminish, meaning you may not feel as full after a meal and may be hungry more often.

But GLP-1 isn’t the only hormone affected by semaglutide. Emerging evidence suggests GLP-1 impacts ghrelin and leptin levels. Ghrelin sends hunger signals to the brain, while leptin helps the body figure when it’s full or hungry.

Gherlin works opposite of GLP-1, meaning that semaglutide may also counterbalance ghrelin levels. Early research also suggests that semaglutide may increase leptin sensitivity, which is associated with healthy metabolic function and weight. However, little research has been done on either, and semaglutide’s exact role in ghrelin and leptin regulation is still undetermined.

What is clear is that once someone stops semaglutide, hunger cues related to ghrelin and leptin become louder. At the same time, semaglutide’s appetite regulation effect quiets. All this contributes to more food cravings and feeling hungry more often, which may make someone eat more than they normally would.

Metabolic Adaptation: The Drop in Energy Expenditure

Many people who take semaglutide for a year or longer report that their weight plateaus, meaning they stop losing weight. This period is referred to as a metabolic set point, which is when someone’s weight aligns with their genetics and environment. If you drop below, your metabolism may actually slow down weight loss to get you back to the set point.

Yet set point isn’t the only thing slowing metabolism. Semaglutide often reduces caloric intake. The body uses calories to stay alive, complete workouts, and get through everyday activities. When calorie intake decreases, the body cuts back on its energy expenditure to preserve calories, which means metabolism slows.

The problem is that slowing may last for years, even after stopping semaglutide. A slower metabolism makes it harder to lose weight and easier to gain it.

The Scientific Evidence of Regain

Clinical trials back the prevalence of weight regain after stopping semaglutide:

• In the STEP-1 trial extension, participants who stopped semaglutide regained two-thirds of lost weight on average.
• In STEP-10, participants regained over 40% of weight within 28 weeks of discontinuing the medication.
• Based on a meta-analysis of multiple clinical trials, people who stopped taking semaglutide regained 21.36 pounds on average.

Yet those clinical trials still offer some hope. People who regained weight not only stopped semaglutide, but also stopped lifestyle interventions, such as consistent workouts or dietary changes. This suggests the right habits reduce the risk of weight regain.

Pillar 1: Pharmacological Strategies for Sustained Success

One of the most effective ways to avoid weight regain is to continue taking the medication. Long-term semaglutide use may help maintain a healthy weight as well as reduce the risk of developing certain chronic diseases. If someone can not tolerate the side effects of semaglutide, other weight loss medications are available.

“After someone reaches their goal weight, I often discuss continuing a GLP-1 medication long term, sometimes at the lowest effective dose,” says Dr. Daniel McGee, board-certified family medicine physician, “This can help maintain their results while we lock in long term healthy habits around protein, strength training, sleep, and daily movement. To help prevent weight regain, it's better to plan medication maintenance proactively rather than stopping abruptly."

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The Maintenance Dose: Continuing Semaglutide Long-Term

Sometimes, a doctor will prescribe a maintenance dose of semaglutide. This is often a lower dosage, taken indefinitely to preserve progress. In one study, adults who continued to take semaglutide at a maintenance dose did not gain weight, while those who switched to a placebo did.

Chronic Management: Treating Obesity as a Chronic Disease

Obesity is a risk factor for many other chronic conditions, including type 2 diabetes, kidney disease, heart disease, and non-alcoholic fatty liver disease. Semaglutide not only helps people lose weight but also lowers the risk for many of these other conditions. As a result, many people take semaglutide as a way to prevent issues like heart disease or non-alcoholic fatty liver disease.

If someone already has type 2 diabetes, semaglutide may also play an important role in regulating blood sugar. A maintenance dose is also commonly prescribed for people with diabetes.

Transitioning to Other Maintenance Medications

Like any medication, semaglutide can cause side effects. The most common include heartburn, nausea and vomiting, diarrhea, constipation, headaches, and burping. While these are usually manageable, some people must stop taking semaglutide due to difficulty tolerating semaglutide’s side effects.

In these cases, a healthcare provider may recommend switching to another weight loss drug, such as Victoza (liraglutide) or Mounjaro (tirzepatide).

Pillar 2: High-Impact Nutritional Strategies

Currently, three forms of semaglutide are FDA-approved (Ozempic and Rybelsus for type 2 diabetes, and Wegovy for weight management). The FDA notes that all work best alongside a healthy diet and regular movement. Stopping semaglutide doesn’t mean you have to pause those dietary or exercise changes. Sticking with a semaglutide diet and workout routines may manage weight after discontinuing the drug.

Prioritizing Protein and Fiber for Sustained Satiety

When on semaglutide and after tapering off, prioritize fiber and lean protein. Both of these food groups support healthy digestion and make you feel full for longer.

Sources of lean protein include chicken, fish, and tofu—though meat that is fried or breaded doesn’t fall into the “lean” category.

Fiber is found in most vegetables and fruits, legumes (lentils, beans, chickpeas, etc.), and many whole grains, like brown rice or whole grain pasta.

Mindful Eating and Identifying Old Behavioral Triggers

Since hunger cues return to normal after stopping the medication, you may experience more food cravings and a desire to eat in response to difficult emotions. To curb emotional eating, practice mindful eating strategies. These include:

• Eat without distractions—that means avoid watching TV or scrolling socials at meal time
• Chew and swallow a bite before taking another
• Focus on the sensation of eating, such as how food tastes and smells
• Put utensils down between each bite

Pay Attention to Calories

When on semaglutide, a low-calorie diet is often recommended. That diet may become harder to maintain after stopping the medication. However, a diet that provides enough calories for your daily needs, instead of too many or too few, can help maintain your current weight and energy levels.

To reach this calorie sweetspot, consider counting how many calories you use and eat each day. The right amount is individualized, since age, gender, and activity level all influence how many calories you need. The FDA has a tool that can help determine your recommended daily calorie intake.

Pillar 3: Tailored Physical Activity for Maintenance

Alongside nutrition, physical activity also helps keep the weight off. At minimum, aim for 150 minutes of cardio and two strength training sessions a week.

The Crucial Role of Resistance Training in Preserving Lean Mass

Strength training helps burn calories, which supports weight maintenance, and builds muscle mass. We often underestimate the importance of muscle, but it can help with so much. Muscle helps us move our bodies, provides the strength for internal processes, and assists with breathing and blood circulation.

Since many people lose muscle as well as fat when on semaglutide, it’s important to strength train at least twice per week to grow or maintain muscle mass. This is an important habit to continue, whether on a maintenance dose or stopping semaglutide.

Aerobic Activity: Optimizing Energy Expenditure for Maintenance

Aerobic exercise (think: jogging, walking, biking, and swimming) helps burn calories and maintain weight loss. The CDC recommends 150 minutes or more of cardio each week, which might look like five 30-minute walks or bike rides. However, even 30 minutes of cardio a week is enough to avoid gaining weight or to support modest weight loss.

Integrating Movement: Finding Sustainable Long-Term Fitness

In one study, people who stopped liraglutide, a weight loss medication that is similar to semaglutide, experienced less weight regain if they participated in a supervised exercise program. While not all of us can access an organized program, there are ways we can hold ourselves accountable and make exercise part of our routine:

• Schedule workouts into your calendar as you would work meetings or meet-ups with friends.
• Ask a loved one to keep you accountable for your movement goals. This could look like a weekly check in via text or meeting up for walks or exercise classes.
• Park further out when shopping so you have to walk more to reach stores.
• Take the stairs whenever possible.
• Consider joining a workout class, run club, or other organized group.

The Long-Term Partnership: Monitoring and Support

Whether you stay on semaglutide, switch to another weight loss medication, or turn to lifestyle interventions alone, monitor progress and any signs of weight regain.

Regular Monitoring of Labs and Body Composition

Throughout your weight loss journey, a healthcare provider may order labs and assess the body composition, determining if you’re successfully losing weight, as well as if the pounds dropped were fat or muscle.

The Power of a Specialist-Led Support System

While you can work with a primary care physician on weight loss, a healthcare provider who specializes in weight management may offer more insight. Ideally, the provider you work with should also have experience prescribing semaglutide to patients and supporting them while on this medication and after.

To determine if a healthcare provider has the right expertise, ask:

• Do you work with patients who take semaglutide? If so, how do you support them while on the medication and if they decide to stop?
• Besides taking semaglutide, what do you recommend to lose weight?
• After a patient loses weight on semaglutide, do you help them avoid weight regain?