For millions of Americans, GLP-1 medications like Ozempic and Wegovy have delivered something that decades of dieting could not: real, dramatic, and lasting weight loss. People find their clothes getting looser as compliments roll in. And for most patients, the cardiovascular and metabolic benefits are genuine and significant.
Dr. Anthony Puopolo, an M.D. who is board-certified in family medicine and trained in both psychiatry and integrative wellness, has observed how well the drugs work for many of his own patients. What he wants GLP-1 users to understand, however, is that there is one important piece of the puzzle that many prescribers are not discussing, and that without it, some of that hard-won progress may be working against them.
The number your prescribing doctor probably may not have mentioned
When a patient arrives at Dr. Puopolo’s office thrilled about their weight loss on a GLP-1 drug, he makes sure they understand one critical fact before anything else.
“Approximately one-third of their weight loss likely came from lean muscle mass, not just fat,” he said. “While losing 50 pounds is a remarkable achievement, understanding the composition of that weight loss is critical for long-term health.”
He was quick to add important context. The muscle loss that occurs on GLP-1 medications is not unique to these drugs, he noted, and is largely proportional to what happens with any significant weight loss. The cardiovascular benefits, he stressed, are real and for most patients likely outweigh the risks. The bigger concern, in his view, is simply that patients are not being given the information they need to protect themselves.
“The evidence suggests most prescribers are not having this conversation adequately, and the gap between what guidelines recommend and what happens in practice is substantial,” he said. The reasons vary, he added, depending on “the provider’s education, setting, time with the patient, and overall approach.”
Why the body gives up muscle during rapid weight loss
The muscle loss that occurs on GLP-1 medications is not a strange or unique drug side effect. Dr. Puopolo explained that it is something that happens with any significant, rapid weight loss, regardless of how that deficit is created.
“Your body doesn’t distinguish between fat and muscle when deciding what to burn for energy,” he said. Muscle tissue, he continued, is metabolically expensive to maintain. “In an energy-scarce environment, the body essentially performs a cost-benefit analysis: ‘Do I really need all this muscle if I’m not using it and food is limited?'”
Two factors make the problem worse on GLP-1 drugs specifically. The first is the speed of weight loss. “The faster and larger the weight loss, the more the body sacrifices muscle along with fat due to limited time to adapt properly,” he noted. The second is appetite suppression. “When appetite is suppressed, people naturally eat less protein,” he pointed out, and protein is exactly what the body needs to preserve muscle during weight loss.
What muscle loss on Ozempic actually feels like
Dr. Puopolo shared that one of the most unsettling things about muscle loss is how gradually it occurs. Most people never connect what they are feeling to their medication.
“Many patients don’t connect their symptoms to muscle loss because the changes develop gradually and are overshadowed by the positive feelings associated with losing weight,” he said.
The earliest signs tend to show up in the lower body. “Patients may notice they’re struggling to rise from a low chair or toilet without using their arms for assistance, taking longer to climb stairs, or relying on the railing more than before,” he cautioned. “These changes often appear before any visible muscle wasting occurs.”
More advanced symptoms can include fatigue, slowed walking speed, reduced grip strength, balance struggles and an increased risk of falls. “These issues become more significant with advancing age,” he added.
Three simple tests to check your muscle health at home
Rather than waiting for symptoms to worsen, Dr. Puopolo recommended three straightforward tests anyone can do at home to monitor their muscle function.
The first is the five sit-to-stand test. “Time how long it takes to stand from a chair five times without using arms,” he instructed. “If this takes more than 15 seconds, muscle function is declining.”
The second involves grip strength, measured with a hand dynamometer if available. “Decline below 27 kg. for men or 16 kg. for women signals concern,” he said.
The third is a simple walking test. “Walking speed below 0.8 meters per second, more than five seconds to walk four meters, indicates functional impairment,” he explained.
The resistance training and protein strategy that actually protects muscle
The most important intervention, Dr. Puopolo stressed, is resistance training, and the minimum effective dose is far more achievable than most people expect.
“The consensus recommendation is at least two days per week of resistance training consisting of one to three sets of eight to twelve repetitions targeting all major muscle groups,” he said. “This translates to roughly 60 to 90 minutes per week total.” Even imperfect effort matters significantly. “The key is consistency over perfection,” he contended. “Even suboptimal resistance training is dramatically better than none.”
On protein, the target is 1.2 to 1.6 grams per kilogram of body weight per day, or roughly 80 to 120 grams daily for most people. The problem is that most GLP-1 users are eating far less than that. “Most patients on GLP-1 therapy are likely eating 40 to 60 grams of protein daily, roughly half of what they need,” he observed.
Critically, he warned, protein without exercise is not enough on its own. “Excess dietary protein without a muscle stimulus can be converted to fat,” he said. But when the two are combined, the research tells a striking story. “Resistance training can reduce lean body mass loss 50% to 95% during weight loss interventions,” he said.
Are people who feel great on GLP-1 medications being set up for problems down the road?
Whether GLP-1 medications are setting patients up for problems later on is perhaps the most pressing question surrounding the GLP-1 era, and Dr. Puopolo was candid with his concerns.
“We genuinely don’t know yet,” he acknowledged, “but the available evidence suggests the cardiovascular and metabolic benefits likely outweigh the muscle loss risks for most patients, provided they take proactive steps to preserve muscle.”
Patients who have lost dramatic amounts of weight and feel great, he said, are probably not headed for disaster. The cardiovascular benefits are substantial. The muscle loss is real but largely preventable with the right lifestyle steps.
“The biggest risk isn’t the muscle loss itself,” he said. “It’s the discontinuation without lifestyle support, leading to fat-predominant weight re-gain and worsened body composition.”
He was equally candid about the limits of what medicine currently knows. “We’re running a large-scale natural experiment, and we won’t know the full 10-year outcomes for another five to seven years,” he said. “The early signals are encouraging, including cardiovascular benefits and preserved function in some studies, but the long-term body composition trajectory, especially with medication cycling, remains genuinely uncertain.”
What every Ozempic user should hear before their first dose
If Dr. Puopolo could put one message in front of every person starting a GLP-1 medication, it would be this:
“This medication will help you lose weight, but it won’t automatically make you healthier,” he said. “What you do alongside it, particularly lifestyle changes, will help determine whether you come out of this stronger or weaker.”
For many people, GLP-1 medications work wonders for their health, and the weight loss is real. The cardiovascular benefits are significant, too. Muscle loss, he emphasized, is largely a solvable problem for patients who know what to do about it.
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More About Our Expert: Dr. Anthony Puopolo is a board-certified family medicine physician with psychiatry training and integrative wellness expertise. He is Chief Medical Officer at LifeMD. He has over 25 years of experience in the medical field. He graduated from Boston University School of Medicine in 1999. He completed a combined Family Medicine and Psychiatry residency program in the U.S. Army at Tripler Army Medical center in Honolulu, Hawaii. He also completed an intensive wellness fellowship with the acclaimed Dr. Andrew Weil, the founder and director of the Andrew Weil Center for Integrative Medicine at the University of Arizona.
Please note: Robin Raven is a journalist covering health and medicine. This article is based on an interview with Dr. Anthony Puopolo and is intended for informational purposes only. It does not constitute medical advice, diagnosis, or treatment. Always consult a qualified healthcare provider before making any decisions about your medication or health regimen.