Ozempic Makes You Lose Muscle, Too. And That Might Be OK.

YOU’VE PROBABLY SEEN the headlines by now: “Weight-Loss Drugs Can Lead to Muscle Loss, Too.” “The Race Is On to Stop Ozempic Muscle Loss.” “Weight-Loss Drugs Could Cause More Harm than Good.” Scary? Sure.

If you’re considering Ozempic or another GLP-1 inhibitor, the news about muscle loss may convince you not to take that step. And if you’re already taking a GLP-1 for weight loss, you may wonder if you should stop.

We can’t tell you what to do. But we can tell you what we know about GLP-1s and muscle loss, and what you can do to minimize it. First, though, let’s review some basic facts about weight loss.

What We Really Lose When We Lose Weight

ANY SUBSTANTIAL CHANGE in your body weight, in either direction, will include a mix of fat and lean tissue. A steroid-free lifter will rarely gain muscle without adding some fat. And weight loss invariably includes some reduction in lean mass. That’s true no matter how you lose it—medication, surgery, or good old-fashioned diet and exercise.

“The rule of thumb is, for every three pounds of fat, it’s one pound of lean,” says Stuart Phillips, Ph.D., a professor of exercise science at McMaster University in Hamilton, Ontario. In other words, you’d expect 75 percent of your weight loss to be fat and 25 percent to be lean mass. Lean body mass, or LBM, includes muscle, bone, organs, fluids, and everything else that isn’t fat.

Even fat isn’t entirely fat. Fat cells contain some water, and they’re held together by a matrix of connective tissues. When you lose a lot of fat, as many people do with GLP-1s, you also lose some of that intracellular water and extracellular protein, both of which count as LBM. Muscle, to be sure, is the largest component of LBM—”probably 60 percent, or thereabouts,” Phillips says.

Let’s run some numbers:

Picture a guy who starts out at 240 pounds. After six months on a GLP-1, he’s lost 40 of them.

If we assume 25 percent was LBM, that means he lost 10 pounds of lean tissue, including perhaps six pounds of muscle. That’s not nothing, but the benefits of losing 30 pounds of fat would almost certainly dwarf the downside of losing a few pounds of contractile tissue.

But what if the proportion of LBM loss was higher—40 percent, say, as recent research has suggested? Now we’re talking about 10 pounds of muscle, which could be more consequential.

Is it, though?

Physiology vs. Feelings

CONSIDER WHY YOU lose weight with a GLP-1: “First, it slows down gastric emptying,” Phillips says. “You feel full sooner and for longer” than you ordinarily would. At the same time, “a central action in the brain suppresses your appetite. You don’t get food cravings. “So you don’t eat as much, because of your stomach being full. But you also don’t feel like eating.” The result is often a massive calorie deficit, one that would be incredibly difficult to maintain on a conventional weight-loss diet.

A calorie deficit of that magnitude is a shock to your metabolism, which is used to a steady supply of carbs and fat from your meals. While you’re celebrating your weight loss, your body wonders how it’s going to feed your brain (like a child on Halloween, the brain runs entirely on sugar), preserve your immune system, and keep blood glucose at a steady level.

The amino acids you have stored in your muscle tissue, with a bit of metabolic magic, can be converted to glucose. At that point, your body sees that protein as a convenient source of fuel.

“In the muscle-centric world, every gram of muscle loss seems like a tragedy,” Phillips says. “But as far as your body is concerned, it’s a low priority.” Bottom line, you give way more fucks about your biceps than your physiology does. That’s why muscle is so much easier to lose than it was to build.

But how much can you afford to lose before your health suffers? Perhaps more than you think.

The heavier you are, the more muscle you have. But especially among older adults, the muscle is typically lower-quality—weaker fibers, with more fat within the muscle cells. And the longer you carry excess weight, the greater the toll it’s likely to take on your ability to move without pain. Each step requires more effort, and puts more pressure on worn-down joints and connective tissues.

That’s why, as Phillips and others have pointed out, there’s no evidence people who lose weight with GLP-1s lose any strength or function. ”If anything, function gets better,” he says. “You can now do things you didn’t do, and maybe didn’t even want to do.”

Which brings us to the actionable part of the story.

Lifting for Losers

SPENCER NADOLSKY, D.O., is an obesity and lipid specialist and co-host, with his brother Karl, of the Docs Who Lift podcast. He’s prescribed GLP-1s to thousands of patients with obesity and/or type 2 diabetes over the past dozen or so years. While there’s a huge range in age, size, and health status, he has one consistent message: “What I tell them is, ideally, we’ll get you to do resistance training to optimize your body composition changes,” he says. Many of them follow the doctor’s advice, “and most of them end up getting stronger.” That’s important for many things, including withstanding aging.

The workouts Nadolsky recommends for patients taking a GLP-1 are no different from what he’d recommend for anyone else. “The exact same principles apply,” he says:

• Train at least twice a week.
• Focus most of your effort on the fundamental movement patterns—squat, hip hinge, push, pull—because they work your body’s biggest muscles. Curls are fun, but they aren’t going to matter much when your goal is to prevent muscle loss.
• Use a full range of motion, and take most of your sets close to technical failure (the point when you can’t do more than one or two additional reps with good form).
• Progressively increase both load (the amount you lift) and volume (the number of sets per week for each movement pattern) over time. Each additional weekly set has a measurable effect on the size of the muscles involved in that movement.

Nauseous Optimism

IT SEEMS OBVIOUS that dietary protein is important for someone trying to minimize muscle loss while taking a GLP-1. If we were talking about a conventional fat-loss program, with the goal of getting close to single digits and maybe seeing an ab or two, we’d recommend at least one gram of protein per pound of body weight.

But there’s a reason why our experts don’t recommend that for someone taking a weight-loss drug: nausea. “It’s a very common side effect,” Nadolsky says. Choking down another chicken breast is the last thing you want to do when you’re still feeling queasy from your last meal. Fortunately, it’s not necessary. Nadolsky recommends about 0.5 grams of protein per pound of body weight per day for his patients taking a GLP-1. “That’s lower than bodybuilders would recommend, but it’s still higher than the RDA,” he notes, and more than adequate to support a large person’s lean body mass.

For a guy who weighs 200 pounds, it should be easy to get 100 grams of protein a day from easily digestible sources, like dairy, eggs, and protein shakes. Your choice of a protein powder can be as simple or complicated as you want to make it. “Whey protein is the best we know of,” Phillips says. It’s lactose free, relatively inexpensive, and easy to find.

If you prefer a plant protein, you have a long list to choose from. “Soy gets a bad rap, but it’s very high quality,” Phillips says. He’s also bullish on pea, hemp, rice, canola, and potato proteins. What matters, he says, is what you prefer, what you can tolerate, what tastes good to you, and what you can afford.

The End of the Beginning

ONE QUESTION WE can’t yet answer: Do GLP-1s have some unique effect on LBM in general, or muscle in particular, that’s different from what happens when you lose weight through diet or surgery? “Not even the drug companies know that,” Phillips says.

Nadolsky isn’t convinced the drugs are doing anything unusual to LBM. Lots of his patients get DEXA scans to assess their body composition, and so far the results are “nothing out of the ordinary.” About 75 percent of the lost weight is fat, and about 25 percent is lean tissue. And the more extreme LBM loss found in some studies? “I’ve just never seen it in thousands of patients,” he says.

Even 25 percent LBM loss may soon be a thing of the past. If you look at any paradigm-changing drug introduced in the past century, from birth-control pills to blood-pressure meds to antidepressants, the first version is always replaced by something better, or by a combination of drugs that boost effectiveness while minimizing side effects. Phillips predicts GLP-1s will have the same trajectory. “This is only the beginning. We’re going to see much more effective formulations coming down.”