Regaining Weight After Semaglutide: How to Beat the Ozempic Rebound and Keep Pounds Off

Semaglutide, the active ingredient in medications like Wegovy, Ozempic, and Rybelsus, has emerged as a significant tool in managing weight and type 2 diabetes. While Wegovy is currently the only semaglutide-based medication approved for weight loss in the United States, all three medications share the same active ingredient. Semaglutide works by suppressing appetite and promoting a feeling of fullness, often leading to substantial weight loss. However, a common concern arises when individuals discontinue semaglutide treatment: weight regain. This phenomenon, sometimes referred to as "Ozempic rebound," can be discouraging, but understanding the reasons behind it and adopting effective weight management strategies can help maintain weight loss after stopping semaglutide.

The Reality of Weight Regain After Semaglutide

The unfortunate truth is that most people regain some of the weight they lost after stopping semaglutide. This isn't necessarily due to a lack of willpower or failure on the individual's part. Instead, it's primarily a natural physiological response to the medication's absence. As Dr. Lauren Lemieux, an obesity medicine specialist, explains, weight gain after semaglutide use is often "the natural consequence of increased appetite and reduced feelings of fullness once the medication has left your system."

Research confirms this observation. A STEP 1 extension study, which followed participants for a year after they stopped taking semaglutide, revealed that they regained two-thirds of their prior weight loss. This highlights the chronic nature of obesity and suggests that ongoing treatment or management strategies are often necessary to maintain improvements in weight and health.

Study Details

The STEP 1 trial (NCT03548935) was a randomized, double-blind, placebo-controlled trial conducted at 129 sites across 16 countries. Participants were adults (aged ≥ 18 years) with a body mass index (BMI) of 30 kg/m2 or higher, or of 27 kg/m2 or higher with at least one weight-related co-morbidity (hypertension, dyslipidaemia, obstructive sleep apnoea or cardiovascular disease), and a history of at least one self-reported unsuccessful dietary effort to lose weight. Key exclusion criteria were type 1 or 2 diabetes and obesity pharmacotherapy 90 days or less before enrolment. Participants were randomized to 68 weeks of treatment with once-weekly s.c. semaglutide 2.4 mg (n = 1306) or placebo (n = 655) (2:1), plus lifestyle intervention. The lifestyle intervention consisted of counselling every 4 weeks on diet (500 kcal deficit per day relative to total estimated energy expenditure at randomization) and physical activity (150 minutes per week). Semaglutide was initiated at 0.25 mg, with escalation every 4 weeks until the 2.4 mg target dose was reached (Figure S1). The STEP 1 extension followed a subset of participants for an additional 45 weeks (a total of 52 weeks off-treatment) until the end-of-trial visit at week 120 (Figure S1). The extension was offered in five selected countries (Canada, Germany, Japan, the UK and the United States) that were representative of the global trial population and aimed to include approximately 300 participants. In Canada, Germany and the UK, all sites with subjects interested in participating in the extension were included (Canada: six sites; Germany: 13 sites; UK: 10 sites). In the United States and Japan, the sites included in the extension (United States: five sites; Japan: three sites) were objectively selected based on those with the highest recruitment in the STEP 1 main phase (using an assumed on-treatment completion rate for the main phase [70%] and an assumed participant willingness to participate in the extension [80%] to determine the number of sites required to achieve the target participant number). All participants from the selected sites could enter the extension, provided they met the extension phase eligibility criteria. To be eligible for the extension, participants were required to have completed treatment with semaglutide 2.4 mg or placebo at week 68 and to provide informed consent for the extension.

From September 2019 to April 2020, 336 participants from the main phase were screened for the extension and 333 entered the extension, including 232 participants who received semaglutide during the main phase (referred to as the “semaglutide arm” hereafter) and 101 who received placebo during the main phase (“placebo arm” hereafter). In total, 327 participants (98.2%) were included in the ExAS (Figure S2). The majority of participants completed the extension (93.7%; n = 312/333). Data from the final week 120 visit were available from site visits for 290 participants (semaglutide arm: n = 197; placebo arm: n = 93).

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During the main treatment phase (from baseline [week 0] to week 68), semaglutide reduced body weight more than placebo (Figure 1A and Tables 2 and S1); observed mean weight loss was 17.3% (standard deviation [SD]: 9.3%) with semaglutide versus 2.0% (SD: 6.1%) with placebo (Table S1). After treatment withdrawal, body weight regain was observed in both the semaglutide and placebo arms (Figure 1A and Tables 2 and S1). Participants regained a mean of 11.6 percentage points (SD: 7.7) of body weight in the semaglutide arm versus 1.9 percentage points (SD: 4.8) in the placebo arm (Table S1). The net mean body weight loss over the full duration of the main treatment phase and off-treatment extension phase (from week 0 to week 120) was 5.6% (SD: 8.9%) in the semaglutide arm versus 0.1% (SD: 5.8%) in the placebo arm (Figure 1A).

Factors Contributing to Weight Regain

Several factors contribute to weight regain after stopping semaglutide:

Increased Appetite and Reduced Satiety: Semaglutide slows down gastric emptying, creating the sensation of being full for longer. Once you stop semaglutide, this effect diminishes, leading to increased appetite and reduced feelings of fullness.
Metabolic Adaptation: When a person restricts their calorie intake, their body enters a state known as starvation. The action the body uses to adjust its energy when reacting to environmental changes, such as weight loss, is called metabolic adaptation. The body enters “starvation mode” when in a calorie deficit, conserving energy and lowering metabolism.
Loss of Muscle Mass: In cases where resistance exercise is excluded from the weight loss regimen, weight loss frequently results in a loss of muscle mass. Losing muscle during weight loss is harmful to long-term weight maintenance since muscle is what burns calories. Muscle mass contributes to a higher-functioning metabolism. Muscle burns greater calories than fat when energy is stored (i.e. when there is no activity).
Return of Old Eating Habits: Some patients experience a return of old eating habits once appetite suppression wears off. Patients who stop or do not follow structured exercise or meal planning may see weight return faster, as well.
Underlying Health Issues: Certain health issues can increase the risk of rebound weight gain, including sleep apnea, hormonal imbalances, or thyroid disorders.

Strategies to Minimize Weight Regain After Semaglutide

While weight regain is common, it's not inevitable. By proactively implementing weight management strategies, individuals can minimize the amount of weight they regain and maintain a healthier lifestyle.

1. Maintain an Exercise Routine

Physical activity is crucial for maintaining weight loss after stopping semaglutide. A post-treatment analysis from 2024 found that keeping up with exercise after stopping GLP-1 receptor agonists was associated with less weight regain. Lemieux encourages patients to build physical activity into their routines from the very beginning, with a long-term goal of at least 250 minutes weekly of moderate intensity physical activity, which has been shown to be helpful for weight loss maintenance. Regular movement is a cornerstone of maintaining weight loss after GLP-1 medications. When you stop these meds, your metabolism can slow, and muscle mass-your body’s calorie-burning engine-may decline if left unchecked. Exercise steps in to keep your metabolism humming, preserve that precious muscle, and support overall wellness. When you exercise, your body undergoes a cascade of beneficial changes that counteract the effects of discontinuing GLP-1 medications.

Endorphin Boost: Physical activity triggers the release of endorphins-your brain’s natural “feel-good” chemicals.
Improved Insulin Sensitivity: Exercise helps your muscles absorb glucose more efficiently, stabilizing those levels naturally.
Muscle Preservation & Calorie Burn: Strength training maintains or builds this muscle, countering the metabolic slowdown that often follows GLP-1 cessation.
Fat Oxidation: Cardio activities ramp up your body’s ability to burn stored fat for fuel, especially when paired with a low-carb or keto diet

We’ve designed these routines to fit busy schedules and all fitness levels. No gym? No problem-most can be done at home with minimal or no equipment.

20-Minute Brisk Walk (3-4 mph): Aim for a pace where you can talk but not sing-about 100-120 steps per minute. Track it with the free “Map My Walk” app, which logs distance, speed, and calories burned.
Stair Climbing (10-15 Minutes): If you’ve got stairs at home or work, climb up and down at a steady pace. It’s a sneaky way to boost heart rate and tone your legs-burning up to 150 calories in 15 minutes.
Jump Rope (5-10 Minutes): Start with 30-second bursts, resting 30 seconds between, and build up. A 10-minute session can torch 100-130 calories and improve coordination.
15-Minute Bodyweight Circuit: Do 10 squats (feet shoulder-width, lower until thighs are parallel to the ground), 10 push-ups (on knees if needed for form), and 10 lunges per leg (step forward, knee over ankle). Rest 1 minute, then repeat 3 times. This hits major muscle groups-legs, chest, core-and burns about 80-100 calories while boosting metabolism.
Resistance Band Routine (20 Minutes): Grab a $10 resistance band online or at a store. Do 12 bicep curls (pull band up to shoulders), 12 shoulder presses (push band overhead), and 12 lateral leg raises (loop band around ankles, lift leg to side). Rest 30 seconds between exercises, repeat 3x.
Dumbbell Option (15 Minutes): If you’ve got light weights (5-10 lbs), try 10 deadlifts (bend at hips, weights to shins), 10 bent-over rows (pull weights to chest), and 10 overhead tricep extensions. Repeat 3x.
10-Minute Core Blast: Lie on your back for 20 bicycle crunches (elbows to opposite knees), hold a 30-second plank (forearms on ground, body straight), and do 15 leg raises (lift legs to 90 degrees, lower slowly). Rest 1 minute, repeat twice.
Stretching (5-10 Minutes): After any routine, stretch-quad stretch (pull foot to glute), hamstring stretch (one leg forward, reach for toes), and chest opener (clasp hands behind back, lift).

Mix cardio (3-4x/week) and strength (2-3x/week) for balance. Start small-10 minutes daily-and build up. These routines don’t just burn calories-they rebuild your body’s resilience. Cardio tackles fat, strength preserves muscle, and flexibility keeps you agile. Together, they mimic GLP-1’s metabolic benefits, helping you maintain weight loss after GLP-1 without feeling overwhelmed.

2. Mimic Fullness Through Strategic Food Choices

Semaglutide slows down gastric emptying, creating the sensation of being full for longer. Once you stop semaglutide, you can mimic this sensation by adding protein to meals. Meals containing protein may help slow digestion. Eating lots of produce, which takes up more space in the stomach but with fewer calories than other foods due to the extra water and fiber content is also helpful.

At Smiley Aesthetics, we recommend nutrition plans that naturally keep you full, energized, and in control-no prescription needed. By focusing on whole foods and strategic eating, you can mimic some of GLP-1’s benefits and sustain your progress long-term. GLP-1 medications work by slowing gastric emptying (how fast food leaves your stomach), reducing hunger hormones, and stabilizing blood sugar.

Ghrelin Surge: Without GLP-1, ghrelin-the “hunger hormone”-rises faster, signaling your brain to eat sooner.
Blood Sugar Swings: GLP-1 enhances insulin release to manage glucose.

Protein, fiber, and healthy fats step in as your allies. Protein triggers CCK and boosts satiety hormones like peptide YY, keeping you full for 3-4 hours. Fiber slows digestion-adding 10g daily can cut hunger by 15%, per studies-and steadies glucose. Fats (like avocado or olive oil) delay stomach emptying, mimicking GLP-1’s effect.We’ve curated diets that align with these principles-each with sample meals and tips to make them yours. For convenience without compromise, we partner with Isagenix.

IsaLean Shakes: 24g protein, 8g fiber-blend Vanilla with water or almond milk for a 250-calorie meal.
Cleanse Day Drinks: Low-calorie, nutrient-rich (e.g., Cleanse for Life)-use on a reset day (1-2x monthly) to curb cravings and detox.
Ionix Supreme: Adaptogen-packed tonic-1 oz daily boosts energy and fights stress-related hunger.

These plans-whether Mediterranean, Keto, or Isagenix-recreate GLP-1’s satiety and stability. Protein and fiber fill you up, fats slow digestion, and low carbs prevent sugar rollercoasters.

Read also: Inspiring Health Transformation

3. Manage Cravings and Emotional Eating

Transitioning off GLP-1 medications can feel like stepping into uncharted territory, and we know that’s not always easy. Cravings, stress, or the urge to eat emotionally might creep up as your body adjusts, but these feelings don’t define you. They’re just moments, and we’ve got gentle, powerful tools to help you navigate them with grace and maintain weight loss after GLP-1. When you stop GLP-1 medications, your brain and body recalibrate, and emotions can play a big role in how hunger feels.

Cortisol’s Impact: Stress triggers cortisol, a hormone that messes with your hunger signals. Cortisol ramps up ghrelin (the “I’m hungry” hormone) and dulls leptin (the “I’m full” signal), making you crave sugary or fatty foods-like reaching for chips during a tough day.
Serotonin & Dopamine Shifts: GLP-1 boosts serotonin, which stabilizes mood and reduces emotional eating. Post-GLP-1, serotonin may dip temporarily, leaving you vulnerable to “comfort eating” as your brain seeks a quick dopamine hit from sweets or snacks.
Emotional Feedback Loop: Stress and cravings can spiral-feeling stressed leads to eating, which might spark guilt, which fuels more stress.

Calming practices like mindfulness boost serotonin naturally, stabilizing your mood without food. Physical movement (even a short walk) releases endorphins, mimicking dopamine’s joy. Journaling or affirmations rewire neural pathways, building confidence over time-studies show just 5 minutes of gratitude daily can cut stress by 15%.

When a craving hits-say, you’re eyeing the cookie jar after a stressful call-it’s like a wave. It feels urgent, but it will pass.

Step 1: Breathe Deeply. Take 10 slow breaths-inhale for 4 seconds, exhale for 6. This activates your vagus nerve, calming cortisol in 60 seconds.
Step 2: Hydrate & Reflect. Sip a glass of water (add a lemon slice for a treat). Then ask, “Am I hungry, stressed, or bored?” Hunger feels physical (growling stomach); emotional cravings feel urgent (racing thoughts).
Step 3: Redirect. Do something small-step outside for fresh air, pet your dog, or play a favorite song. Even 2 minutes shifts your focus.

Calming your body calms your mind, easing cravings before they take hold.You don’t have to do this alone-connection is a craving-buster. Reach Out: When you’re tempted to binge, text a friend or family member-“I’m feeling off, can we chat?” Even a 5-minute call shifts your focus. Join a Group: Look for local or online wellness groups.

If you do overeat-say, you polished off a pint of ice cream-don’t spiral into guilt. It’s a moment, not your story. Reset with One Choice: Pick one healthy action-drink water, eat a veggie-packed lunch, or walk 10 minutes. Learn from It: Ask, “What triggered this?

These strategies-breathing, journaling, moving, connecting-build a bridge between your emotions and actions. They boost serotonin and endorphins, quiet cortisol, and give you power over cravings, just like GLP-1 did. You’re not fighting your body; you’re teaming up with it. Every time you choose a breath over a bite or a walk over worry, you’re rewiring your brain for resilience.

4. Address Potential Hormonal Imbalances

If you’ve been working hard to maintain weight loss after GLP-1 medications, but the scale isn’t budging-or worse, creeping up despite your best efforts-we want you to know it’s not all on you. At Smiley Aesthetics, we’ve seen how weight gain isn’t always about diet or willpower. Hormones-like thyroid, estrogen, testosterone, or cortisol-can quietly shift the scales, and we’re here to help you uncover if they’re the missing piece. Hormonal imbalances can make weight maintenance feel like an uphill battle, but with our Bioidentical Hormone Replacement Therapy (HRT), we can restore balance and support your journey.

Your hormones are like a symphony-when they’re in tune, your body hums along beautifully. But when they’re off-key, even small changes can affect your weight, energy, and mood. Stopping GLP-1 medications can amplify these shifts, as your body adjusts to new hunger and metabolic signals.

Thyroid Hormones (T3 & T4): Your thyroid is your metabolism’s maestro. When it’s underactive (hypothyroidism), T3 and T4 levels drop, slowing your metabolic rate by 10-20%. That means burning 200-300 fewer calories daily-even if you’re eating the same. You might feel sluggish, cold, or see the scale tick up despite a solid diet.
Estrogen Imbalance: Too much or too little estrogen (common in perimenopause or menopause) can steer fat to your midsection. High estrogen boosts insulin resistance, making sugar turn to fat faster-think belly weight that won’t budge. Low estrogen slows metabolism and ramps up cortisol, adding stress-related pounds.
Testosterone Decline: In both men and women, low testosterone (which drops with age or stress) reduces muscle mass-your calorie-burning engine. Losing just 1-2 pounds of muscle cuts your resting burn by 10-20 calories daily, piling up over weeks.
Cortisol Overload: Chronic stress floods your system with cortisol, raising blood sugar and triggering fat storage, especially around your abdomen. Post-GLP-1, without its calming effect, cortisol can spike hunger-leading to cravings for carbs or sweets. Ever raided the pantry after a tough day?
Insulin Resistance: GLP-1 meds improve insulin sensitivity, but stopping them can tip the balance. Excess insulin signals your body to store fat instead of burn it-think of it locking calories away.

Hormones influence hunger, fat storage, and energy use, so when they’re off, maintaining weight loss after GLP-1 gets tougher. But here’s the uplifting truth: we can test, tweak, and turn it around together. Not sure if hormones are your hurdle? If you’re nodding, a simple hormone check could reveal what’s holding you back.

5. Continue with Professional Guidance

Working with a team of professionals, such as an obesity specialist, personal trainer, and registered dietitian, may help you keep forward momentum for long-term weight management. It’s hard to lose weight by yourself. Consulting with professionals can help you discover new ways to manage your weight.

6. Lifestyle Adjustments

Make Sleep a Priority: Lack of sleep can cause weight gain. In fact, getting 7-8 hours every day provides you with the energy you need to stay active-which is vital for managing weight loss.
Stress Management: Unmanaged stress will increase the level of cortisol beyond what is considered normal, leading to unhealthy changes such as weight gain.
Mental Health: Maintaining a healthy mind is crucial for managing weight. However, factors like anxiety and depression create mental unwellness so it is important to talk with your doctor or healthcare provider regarding your mental health.
Healthy Diet: Intermittent Fasting: For some, this can be helpful in maintaining weight after stopping semaglutide. Planning out and prepping meals beforehand enables you to make healthier choices.

7. Consider Restarting Semaglutide (If Appropriate)

You could start semaglutide again if you stop its use and regain weight after your initial treatment. However, the drug is not a short-term weight loss option to be used multiple times or to lose a few pounds every so often.

Lemieux suggests approaching Wegovy use as you would any other medication for a chronic condition. If you gain weight back quickly after stopping semaglutide, Lemieux recommends taking a close look at everything that’s changed since discontinuing the medication. You may not realize just how much your lifestyle has changed after stopping semaglutide. To help you identify patterns that might contribute to rapid weight gain, consider keeping up with daily food tracking and an activity journal, as well as speaking with a doctor to rule out underlying causes of weight gain. While a doctor may place you back on semaglutide, Lemieux added that not everyone responds to Wegovy. Other weight loss medications may be a better fit.

Semaglutide: Long-Term Use and Considerations

Semaglutide has been used for weight loss in clinical trials for up to 104 weeks, or 2 years. Ozempic and Rybelsus are intended for long-term use in managing type 2 diabetes. The duration of Wegovy use for obesity may vary depending on individual goals and needs, underlying health conditions, and side effects.

The prescribing doctor will work with you to create a treatment plan that can be reassessed and adjusted as needed. Semaglutide curbs your appetite. When semaglutide is stopped, appetite will increase. To work around your appetite, you’ll have to make lifestyle changes in order to maintain the weight. How long you stay on semaglutide depends on your situation. Some people need it for a long time to keep the weight off, while others only need it for a short time. Since obesity is a long-term condition, some people may need ongoing treatment.

"Wegovy is intended for long-term use for weight loss and weight loss maintenance," Lemieux explained. "Therefore, it should not be started with the intention to stop and then restart if the weight comes back on. Be wary of working with any provider who promises that it can be used short-term and have permanent results.”

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