Are Weight-Loss Meds Shrinking Your Muscles?

When Andrew Burton began taking Mounjaro over a year ago, his goals were simple: Lose some of the extra pounds that he had put on with the pandemic and improve his cardiometabolic profile, since he has a strong family history of heart disease. And while the weight came off with the help of the prescription medication—he’s down 51 pounds to date—what the 57-year-old didn’t expect was that his fitness would also take a nosedive.

In fact, the one-time Ironman triathlete says he felt noticeably more fatigued on his bike rides and could barely eke out a three-mile training run. His doctor ordered a body composition scan, and discovered that along with the fat, Burton had also lost a significant percentage of his muscle.

“While I was thrilled at the weight loss, I was shocked at the loss of muscle mass,” says Burton, an attorney based in New York City. “And although I relish morning workouts, the nausea I felt in the morning, especially in the days immediately following the injection of the medication, made getting in a workout more challenging.”

After speaking with his doctor to come up with a few fix-it strategies, Burton now makes an effort to hit the weights at least twice a week and has tried to up his protein intake through meals and shakes. Result: He’s noticed a substantial improvement in his fitness and strength. “It took a while, but I think I’ve figured it out,” he says.

Burton is a recreational athlete in tune with his body’s needs. But many of the other estimated 5.6 million weight-loss drug users in the U.S. (a number that has grown 40-fold in the past five years, according to one medical research firm) don’t fully understand the bigger picture ramifications of these medications. Beyond shedding “vanity muscles” and Ironman-worthy quads, there are very real health implications for muscle loss, especially as you age. If you’re considering obesity drugs, do you know what you’re signing up for?

There’s no doubt that the newest generation of weight-loss medications has made a seismic impact when it comes to obesity and health. About 42% of adults in the U.S. have obesity, and with it an increased risk of everything from heart disease and stroke to type 2 diabetes and certain types of cancers, per the Centers for Disease Control and Prevention (CDC). In fact, an estimated 2.8 million people die each year worldwide as a result of being overweight or obese, according to the World Health Organization.

While obesity numbers have climbed at a relatively steep rate over the decades (obesity prevalence increased from 30.5% to 41.9% over the past two decades, per the CDC), most of the weapons employed in the fight against body fat have been ineffective at best—and dangerous at worst.

So when the drug Wegovy (semaglutide) was approved by the FDA in June 2021, it marked the start of a new era in the so-called battle of the bulge. The drug is designed to work on a hormone in the gut called glucagon-like peptide-1 (GLP-1) that is involved in appetite and weight regulation, slowing digestion, blunting cravings, and reducing blood sugar levels. “From the very beginning, we saw an average weight loss with Wegovy that was 1.5 to two times more effective than previously available medications,” notes Robert F. Kushner, M.D., a professor of medicine in the department of endocrinology at Northwestern University’s Feinberg School of Medicine in Chicago, IL, who has led some of the key research involving semaglutide and weight loss.

Just how effective? A 2021 study published in the New England Journal of Medicine found subjects who took 2.4 milligrams (mg) of semaglutide once a week—while making other lifestyle changes like paying attention to portion size and increasing physical activity—lost an average of 14.9% of their body weight in 68 weeks, taking off an average of 33.6 pounds and losing an average of 5.3 inches off their waistline. Up to a third of the participants who were treated with semaglutide lost at least 20% of their baseline weight—a number that stands close to the amount you might see one to three years after bariatric surgery, according to the study.

A second medication, Mounjaro (tirzepatide), which also mimics GLP-1 along with another appetite-regulating hormone called glucose-dependent insulinotropic polypeptide (GIP), has shown even better results. (As of now, Mounjaro is only approved for diabetes; the drug is expected to receive FDA approval for weight loss by the end of 2023.) In a 2022 study published in the New England Journal of Medicine, participants who received the highest doses (15 mg) had an almost 21% weight loss—dropping an astonishing 52 pounds on average after 72 weeks; those on the lowest dose (5 mg) still had an average of 15% weight loss, or 35.5 pounds, per the study.

A third medication on the horizon may even outshine these eyebrow-raising results. Phase 2 trials of retatrutide, a new weight loss drug being tested by Eli Lilly, has been shown to help people lose an average of about 24% of their body weight over 48 weeks, or about 58 pounds on average, according to a recent study in the New England Journal of Medicine.

“I’ve been working in the obesity field for 40 years and been involved with more than 40 clinical trials of potential obesity treatments, and this is the most exciting time I’ve seen,” notes Patrick O’Neil, Ph.D., a professor in the College of Medicine at Medical University of South Carolina (MUSC) and director of MUSC’s Weight Management Center in Charleston, SC. “We’re observing levels of weight loss that have just not been reported before.”

When the number on the scale shifts down, most people assume they’re saying goodbye to all the bad stuff they don’t want—namely, excess body fat, or adipose tissue. And with big-time weight loss, that’s generally true. But that’s not the only thing that gets shed: Muscle also disappears alongside that fat.

“About 20% to 50% of any type of substantial weight will be from muscle,” explains Caroline Apovian, M.D., the co-director of the Center for Weight Management and Wellness at Brigham and Women’s Hospital in Boston, MA.

“We expect about a quarter to a third of all the weight lost is going to come from lean tissue, with the remaining three-fourths to two-thirds coming from fat,” agrees Dr. Kushner. That’s because by drastically cutting back on calories, your body is searching for sources of both protein and fuel—and your muscles are a prime target.

Some of that muscle loss is quite large: In the Wegovy 2021 clinical trial, almost 40% of the weight people lost came from lean mass, including muscle. (While study subjects were counseled to aim for 150 minutes of exercise per week, such as walking, they did not follow a specific fitness program.) “With these medications, because it is such a large amount of weight being lost, a larger percentage of it comes from lean mass,” explains Sean Collins, Ph.D., a professor of exercise physiology at the University of Lynchburg in Lynchburg, VA, and the chair of the Strength and Conditioning Special Interest Group for the American College of Sports Medicine.

“Lean mass” doesn’t only mean muscle—though that’s a lot of it. It means you’re losing bone and organ tissue, too.

“When you reduce the number of calories you take in, you’ll mostly burn fat as fuel,” explains Collins. Fat is the body’s most concentrated and readily accessible source of energy and is stored largely in adipose tissue. But if you aren’t consuming enough calories to keep up with the needed level of fuel to support basic bodily functions and activity, “your body will turn to other sources, including protein in the form of muscle tissue,” says Collins. “It will utilize muscle to make sure you have enough energy to run the heart, lungs, brain, and other organs, along with your daily activities.”

And that’s the thing with these weight-loss meds: People are cutting their calorie intake so far below their previous levels that the body needs to draw on energy sources beyond fat to support, well, your daily existence.

As you get older, this muscle loss is especially problematic. You naturally lose muscle as you age, a process known as sarcopenia, which is the gradual loss of muscle mass, strength, and function. It’s a major contributing factor to increased frailty, leading to more falls and fractures. Muscle mass decreases about 3% to 8% per decade beginning around at age 30, and speeds up even more after age 60.

“If you take a 55-year-old individual who has lost 15% of his or her body weight compared to a 25-year-old, we can expect the amount of muscle mass lost is going to be more significant because they are starting off with less muscle to begin with,” notes Dr. Kushner.

While your goal may be to say “so long” to that extra poundage, the loss of lean muscle can work against you in a number of ways. Of course, there’s the aesthetic appeal—who doesn’t want toned arms and strong legs? But there’s more to muscle than filling out a pair of jeans. “When you lose muscle, you lose a functional unit,” says Collins. “There are a lot of additional benefits that muscle mass brings.”

In fact, having adequate muscle in your body is quite literally a matter of life and death. Research shows a direct relationship between lower levels of skeletal muscle and all-cause mortality: One recent meta-analysis of 16 studies found a 57% increased risk of dying from any cause among subjects with the lowest levels of skeletal muscle, with numbers even higher among those with a body-mass index (BMI) over 30, which is the obesity range.

Muscle plays a central role in other ways as well:

It Makes You Move

“Muscle’s main function is moving bone,” says Collins. “It allows us to move, and that is what our bodies are designed to do.”

Skeletal muscles are attached to bone, allowing you to walk, run, jump, push, and pull, so you can do everything from get dressed to chew gum. They also constantly contract without your even thinking about it, so you can stand up or sit down without falling over.

As you get older, the less muscle you have, and the harder it can be to do daily activities like carrying groceries in from the car or hauling your laundry basket. “[Muscle loss] can have a big impact on your quality of life, whether that’s climbing stairs, going for a brisk walk, or being able to catch yourself if you stumble,” says Dr. Kushner. “We don’t want to make people weaker or less fit as they are losing weight.”

It Maintains Your Metabolism

The irony of losing muscle while on weight-loss drugs is this: Without muscle, your ability to shed pounds is greatly hindered. “Muscle is the only organ in the body that has a dramatic effect on burning energy,” says Dr. Apovian. “Your total energy expenditure is directly related to how much muscle mass you have.”

The reason? Muscle plays an especially pivotal role in resting metabolism—the amount of energy your body needs to function at rest. Your resting metabolic rate (RMR) accounts for 60% to 75% of the calories you burn each day (the rest comes from physical activity and the digestion of food). In truth, muscle may not burn as many overall calories as once thought (by some estimates it’s about 4.5 to 7.0 calories per pound of body weight per day), but that’s still two to three times more than the amount of calories fat burns.

“Muscles are like the cylinders in a car engine,” explains Collins. “If you lose those cylinders, you lose the amount of energy you can potentially burn—it’s like going from a V8 engine to a four cylinder. So, while you’re losing weight, you are also losing some of that metabolic component.”

And as you get older, that number of cylinders shrinks even more as your rate of muscle loss speeds up. “If you burned 1,500 calories a day at rest when you were 20, by the time you’re 60, you may only be burning 1,200 calories,” says Dr. Apovian.

That’s a key consideration if you decide to go off the weight-loss medications, since you may experience a weight rebound—and a lower metabolism means you’ll burn even fewer calories throughout the day.

It Protects Against Bone Loss

We lose bone mineral density as we get older, just like we lose muscle mass, which can increase the risk of osteopenia and osteoporosis. Having more muscle can protect against that bone loss. As a study published in the Journal of Clinical Endocrinology and Metabolism pointed out, the dynamic load that muscle imposes on bone as it pulls it to move has a positive effect on bone mineral density, with bone size rising along with lean muscle mass. Furthermore, other studies have found that muscle loss may contribute directly to bone loss by increasing bone resorption by osteoclasts (the cells responsible for breaking down bone).

It Helps Fight Chronic Illness

Among its many other important roles, muscle has been shown to help reduce the risk of diabetes, heart disease, and other chronic ailments. For example, in the case of diabetes, resistance training increases the delivery of glucose to muscle cells and improves insulin sensitivity. Maintaining skeletal muscle can also reduce inflammation in the body, reducing heart disease risk, and is associated with lower blood pressure.

If you already have some of these chronic conditions, having adequate muscle can improve your outcome, says Collins. “If you have more muscle, you have a better risk profile,” he notes.

All of this may leave you wondering where to turn if you are on, or considering going on, an anti-obesity medication. While more doctors are making it a point to bring up muscle loss in their conversations with their patients, not everyone is getting the counseling they should before going on the meds. And even among those who are, the message may not be getting through. Burton, for one, said that while his doctor was clear that he should be doing some strength training, he failed to take him seriously at the onset. “I was nauseous a lot from the medications, so I didn’t always want to exercise, and I didn’t think it was a big deal to do strength training since muscle had never been an issue for me,” he says. It was the results of his body scan that ultimately got him back on board with lifting weights.

If you’re concerned about losing muscle mass along with body fat while taking weight-loss medications, there’s some good news: You can slow down the loss, and even stave it off with a few key lifestyle changes.

Eat More Protein

Protein is a crucial component of muscle tissue, so it makes sense that getting enough of it in your diet is key toward maintaining your muscle mass. “Protein makes up the largest proportion of tissue structure in the body, including muscle, bone, and blood cells,” says Collins. “All of these things require protein from food as a base to build.”

The current recommended daily allowance (RDA) of protein is 0.8 grams of protein per kilogram of body weight (or 0.36 grams per pound) per day. Based on that recommendation, a 140-pound person would need to consume a minimum of 53 grams per day to stay healthy; a 180-pound person would require 67 grams.

But many argue that number is too low, especially if you are trying to maintain or add muscle. “The RDA is there just to get by—if we change our lifestyle, you also have to change your nutrition strategy,” notes Collins. “If I’m in a calorie deficit because I am using a weight-loss medication and I am not eating enough food, some of that protein is going to be used for fuel. And the only way to limit how much of that is going to be used from muscle is to get it from your diet.”

Age is also a factor. “People need more protein as they get older,” says Dr. Apovian. “The RDA was originally established for lean young men in their twenties. We now know that individuals over age 65 need at least one gram of protein per kilogram of body weight, and maybe as much as 1.5 grams per kilogram.” She’s currently conducting research to see if supplementing with a protein powder can help offset muscle loss in patients who are taking Mounjaro.

“We know that if you are on a weight-loss program and only taking in about 1,200 to 1,500 calories a day, you simply won’t be able to get enough protein to meet your body’s needs,” she says. A person who weighs 150 pounds would need to get in 105 grams of protein a day if they were to reach that 1.5 grams-per-kilogram goal, she adds. “Without the additional 20 to 40 grams of protein supplement, it would be very hard to hit that number.”

Add in Strength Training

You can eat all the protein you want, but it won’t magically transform into bigger biceps. To increase muscle mass—and prevent its loss—you need also to do some form of regular resistance, or strength, training. That’s especially true if you are taking weight-loss drugs or otherwise drastically reducing your calorie intake: You need to rebuild the muscle that’s been lost, or at least prevent your body from cannibalizing that lean tissue by maintaining adequate levels of muscle mass.

How exactly does that work? In a nutshell, challenging your muscles to hoist weights causes tiny microtears in their fibers; the body responds by generating more fibers to repair those microtears. Keep those challenges coming, making them progressively harder as you gain strength, and your body will continue to increase muscle mass.

“Resistance training is crucial when it comes to preventing the loss of muscle tissue,” insists Dr. Apovian. “If you don’t do it, you will lose muscle, and if you go off the medications, you will almost definitely regain the weight.” The CDC’s Physical Activity Guidelines for Americans recommends strength training at least twice a week, working all major muscle groups (legs, hips, back, abs, chest, shoulders, and arms), along with doing 150 minutes of cardio.

That doesn’t mean you have to sign up for a pricey gym membership or start hoisting heavy dumbbells. Research has shown that lifting lighter weights—or even your own bodyweight—can also help maintain muscle mass. “You can do lower loads but then you just need to do more reps,” says Collins. “The main goal is to tire out the muscles.”

Basic bodyweight exercises that hit several muscle groups at once—think squats, lunges, push-ups, pull-ups, and planks—can also yield big benefits. “Repetition is key,” says Collins. “The more you do, the better your brain gets at telling your muscles how to do it.” You can even incorporate household items, like using milk jugs or soup cans to strengthen your arms and shoulders, or just standing up and sitting down into a chair, he adds.

Include Aerobic Activity

While doing aerobic exercise like brisk walking or swimming won’t necessarily pack on muscles, it does work one of your body’s most important muscles—the heart. “The biggest health concern facing us today is cardiovascular disease—it supersedes everything else in terms of cause of death for older individuals,” says Collins.

To meet the physical activity guidelines of 150 minutes of physical activity, you can aim to do 30 minutes five days a week or break it down into even smaller chunks. “We call it ‘exercise snacking,’’ notes Collins. If you do three 10-minute bursts throughout the day—like standing up and doing some calisthenics or taking a walk around the block—that can add up to the recommended minimum.

“Different muscle fiber types benefit from different activities,” he adds. Some muscles will benefit from cardiovascular training, others respond more to resistance training. In the end, it’s important to include both types of exercise, notes Collins.

When patients come into Dr. Kushner’s office looking to take weight-loss medications, he counsels them on a number of things: how to use the medication; potential side effects; and when they will start to see results. And, importantly, he also takes time to talk to them about the need to include strength training using resistance bands, dumbbells, or body weight, advising them to seek the help of a trainer to establish a plan if it’s not too expensive. He also recommends including other regular activity like brisk walking. At the same time, he calculates their protein needs based on 1.2 to 1.5 grams of protein per kilogram of body weight, and provides advice on good high-protein sources. “This range is a reasonable target,” he says.

It’s changes like these that will ultimately lead to long-term success and help those who decide to stop taking weight-loss medications in the future to avoid piling the pounds back on.

Future weight-loss medications are also being developed to halt the rate of muscle loss compared to fat. One of these, bimagrumab, has shown a lean mass gain of 4.5% in early clinical trials while promoting fat loss. (The medication is a monoclonal antibody originally designed to treat muscle loss and weakness from disease; it works by binding to and inhibiting a protein involved in the breakdown of muscle tissue.)

In the meantime, experts are working on developing guidelines for people taking weight-loss drugs to maximize their results while minimizing some of the side effects. “The goal of taking these medications isn’t just to lose weight—it’s to improve your health,” explains Dr. Kushner. “And you can’t have optimal health without the right fitness and nutrition.”

For Burton, hitting the weights has paid off, giving him some renewed energy and strength. And, he adds, his bloodwork shows his cholesterol and glucose levels are the healthiest he’s ever had. “My blood pressure is so good I’m off my blood-pressure medications!” he says. “The weight lifting is also a little addicting, so I’m more into it.” It’s a long-term investment in his health that he plans to keep up, regardless of whether he stays on the weight-loss drugs.