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About four out of every 10 Americans are obese, according to the Centers for Disease Control and Prevention. Obesity is a chronic condition involving changes in how the body regulates hunger, fullness, and metabolism.

“Many people think obesity is only about diet and exercise. While healthy habits are essential, biology and genetics also play an important role,” said Donnell Jones, CRNP, UPMC Central PA Medical Weight Management Center. “Hormones, metabolism, medical conditions, medications, and inherited traits can all influence body weight as well.”

One of the most effective medication treatments for obesity is a group of medications called glucagon-like peptide-1 (GLP-1) receptor agonists, or GLP-1s.

UPMC Medical Weight Management prescribes only GLP-1 medications approved by the Food and Drug Administration. The three GLP-1 medications approved by the FDA to treat obesity include:

• Liraglutide (Saxenda®/Victoza®)
• Semaglutide (Wegovy®/Ozempic®/Rybelsus®)
• Tirzepatide (Zepbound®/Mounjaro®)

GLP-1 medications can lead to an average weight loss of 10% to 20% over 12-24 months when used alongside healthy diet and exercise changes. Weight loss outcomes are reduced when lifestyle modifications are not implemented.

How Do They Work?

GLP-1 drugs work by giving the body extra GLP-1 hormone. Effects of this hormone on the body include:

• It helps your body switch from storing fat to using fat as fuel.
• It helps your body respond better to insulin so sugar goes into your cells for energy instead of turning into fat.
• When sugar is used for energy instead of being turned into fat, your liver doesn’t store as much extra fat.
• Increasing your satisfaction with the food you have eaten.
• Sending signals to the brain that reduce your hunger and thoughts about food.
• Slowing down how quickly the stomach empties its contents, so you feel full sooner and for longer.

These effects last as long as you keep taking a GLP-1 medication.

What Happens When You Stop GLP-1s?

Many people wonder what happens when they stop taking medication for weight loss. Between one-third and one-half of people eventually stop taking it.

Weight gain

Most patients may experience rebound weight after GLP-1s, especially if lifestyle habits don’t support long-term maintenance.

When you stop taking a GLP-1, the drug’s effects gradually wear off. Your brain no longer receives signals that reduce your appetite. You may think about food more often or notice food in your environment that you overlooked while taking the drug. Your stomach also digests food quickly, making you hungry sooner after meals.

As a result, you tend to eat more food and may eat more often than you did while on the drug. Consuming more calories than you burn through physical activity and daily living can lead to weight gain.

These changes after stopping a GLP-1 mean that rebound weight gain after GLP1 is common.

Other effects

Other physical effects can occur after you stop taking GLP-1 medications, including:

• Metabolism may be lower after weight loss
  • “ Any time we lose weight, with or without medication, the body burns fewer calories,” said Ms. Jones. “After stopping a GLP1 the appetite may rise while calories being burned may still be lower, which can make weight regain occur.”
• With even mild weight regain your body might start producing higher levels of insulin again and in return need to start storing more fat again.
• Fat loss in your liver could stop or possibly reverse.
• One study has also found that the risk of heart disease, heart attack, and stroke increased after people stopped taking a GLP-1.
• People who lost muscle mass while taking a GLP-1 may not regain it after they stop the medication leading to a slower metabolism.
• The risk of complications from obesity can also increase after you stop taking semaglutide or tirzepatide.
• Your blood sugar may increase slightly, especially if it was higher before you started the medication.

Planning to Stop Taking GLP-1s

Not every person who stops taking GLP-1s regains all the weight they lost. There are also ways to reduce the weight you might gain and to keep building muscle after stopping GLP-1. Talk to your doctor first if you need or want to stop taking GLP-1.

Your doctor can monitor your blood sugar to see if it changes after you stop the medication. Your doctor can also monitor any risk factors you may have for heart problems, such as blood pressure and cholesterol levels. You can also ask your doctor to check the health of your liver because liver fat is common in people with obesity.

Physical Activity and Strength Exercises

Muscles are essential for maintaining and improving your metabolism. The more muscle you have, the more calories your body burns — even at rest. So building and keeping muscle helps your body use energy more efficiently and makes it easier to maintain weight loss. More muscle = higher metabolism = more calories burned, even when you’re not exercising.

Building and maintaining muscle is important before starting a GLP-1 medication, while you’re on it, and even if you decide to stop it. Keeping your muscle strong helps protect your metabolism, burn calories more efficiently, and makes it easier to lose weight and keep it off long-term.

You can keep or build your muscles by continuing, starting, or increasing muscle-strengthening exercises.

If you haven’t already done weight training, talk to your doctor about how to start. Many people can begin with light resistance exercises for strength training and then build up to more weight training. Examples of light resistance activities can include:

• Calf raises – hold onto a counter or chair for balance if needed.
• Body-weight squats – no weights required; sit back like you’re lowering into a chair.
• Wall sits – lean against a wall and hold for 20–30 seconds, then rest and repeat.
• Plank hold – on the floor, or against a counter/table if a full plank feels too difficult.
• Glute bridges – lie on your back with knees bent and slowly lift your hips, then lower.
• Side leg lifts or banded side steps – helpful for hips, thighs, and balance.
• Resistance band exercises – search YouTube for “beginner resistance band workout.”
• Chair exercises – search YouTube for “beginner chair workout” if standing or floor exercises are challenging.
• Goal: Start with 5–10 minutes per day. Consistency is more important than intensity — small efforts done regularly make a big difference.

Getting some aerobic or cardiovascular exercise each week is also important. The American Heart Association recommends at least 150 minutes of moderate or 75 minutes of vigorous activity weekly. Studies show that people who exercise regularly while using a GLP-1 medication and continue exercising after stopping it tend to have less weight regain and are more likely to maintain their weight loss.

Healthy Eating Tips

While some return weight gain is expected, people who eat a healthy, balanced diet are likely to regain less weight after they stop taking a GLP-1. Implementing lifestyle changes such as a healthy diet and increased activity levels can help to slow weight regain.

Eating  a healthy, balanced diet doesn’t happen automatically for most people. Planning, preparing your meals, and thinking about what to eat each week can reduce spontaneous or unhealthy eating. The following tips can also help you eat a healthy diet:

• Avoid fast food.
• Cut down on the amount of sugar and simple carbohydrates in your diet. Your body digests these foods faster than other foods, so you feel hungrier sooner.
• Drink water instead of soft drinks or other drinks with sugar in them.
• Limit eating out. Restaurant meals usually have bigger portions and contain more sugar, sodium, and fat than meals made at home. If you eat out, pay attention to calories on the menu or look for choices with fruits, vegetables, and lean protein. You can split a meal you order before eating and save the other half for another meal.
• When you do eat out, try to choose grilled, baked, or roasted foods instead of fried foods. Look for words like grilled, baked, steamed, or fresh — and avoid fried, crispy, smothered, or loaded.
• Eat food with lots of fiber. Fiber helps you feel fuller for longer, so you don’t get hungry as quickly. Food with lots of fiber includes vegetables, fruits, and whole grains.
• Eat foods with lean protein. Protein helps your body build muscle and increases your metabolism, allowing you to burn calories faster. Healthy foods with lean protein include poultry, fish, nuts, beans, and legumes.
• Reduce the amount of alcohol you drink because the body converts alcohol into sugar.

UPMC designs its medical weight management programs to support you beyond medication. From nutrition counseling and classes to long-term lifestyle planning, to meal replacement programs and support groups, we help you stay on track for the long haul, even if you stop taking GLP-1 medications.