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How GLP-1s fit into my clinical practice

Writer: Lisa Arshawsky
Lisa Arshawsky
3 days ago
8 min read

What the research says about muscle, who these medications are really for, and how I decide in my practice.


GLP-1 medications might be the most judged prescription in women’s health right now. Spend five minutes online and you’ll see them called cheating, or dangerous. And almost nobody saying those things knows why a particular woman is on one. They don’t know her A1c, her liver enzymes, her blood pressure, her family history of heart disease, the food cravings that won’t stop driving her to overeat, or what the last three years of perimenopause did to her body.


That’s not to say there’s no misuse - there is. People can now buy peptides online without any medical oversight. There have always been women in an active eating disorder who misuse medication, and they need a different kind of support. And there’s a large share of women who haven’t yet seen what their body does with more muscle, more movement, more protein, real food, balanced hormones and better sleep. For them, a GLP-1 without that foundation won’t solve the real issues. Even then, though, it can be what brings down inflammation and enough weight that she finally feels ready to lift and eat well.


Then there’s the evidence. In the SELECT trial, semaglutide reduced major cardiovascular events by 20% in people with established heart disease and overweight or obesity (no diabetes required). Tirzepatide is FDA approved for moderate to severe obstructive sleep apnea in adults with obesity. Semaglutide is approved for MASH (the more advanced form of fatty liver disease), and in the FLOW trial it slowed kidney disease in people with type 2 diabetes. These medications improve insulin resistance and blood sugar, lower inflammatory markers like CRP, and quiet the constant food noise so many of my patients describe. There’s even early research on alcohol use, though that’s still in small trials. That isn’t vanity medicine.


The muscle question

I recently sat in on a talk by Dr. Bill Campbell, a body composition researcher at the University of South Florida. His lab focuses on how to lose fat without losing the tissue you need to keep.


Did you know that when people lose weight through dieting alone (no medication, no exercise), roughly a quarter of what comes off is fat-free mass? It’s consistent enough in the obesity literature that researchers call it the “one-fourth rule.” Fat-free mass isn’t all muscle, by the way. It includes water, glycogen, organs and connective tissue, and skeletal muscle makes up only about half of it. But if you’re losing fat-free mass, some of that is muscle.


Most people assume you lose more muscle on a GLP-1 than on a diet. The research so far doesn’t really show the drug itself is the problem. In the tirzepatide trial that scanned body composition, about a quarter of the weight lost was lean mass, right in line with dieting. Semaglutide’s scan data (STEP 1) ran higher, closer to 40%, but the overall ratio of lean to fat still improved because so much fat came off. Where people get into trouble is speed and intake. Sometimes appetite is suppressed so much that a woman is barely eating, and barely eating protein. Then she’s in a steeper deficit than most diets would ever ask for, and the faster weight comes off, the more lean mass tends to go with it.


Now layer in midlife. Women who aren’t on estrogen and testosterone are already losing muscle as hormone levels fall. That matters for more than how she looks, because skeletal muscle is the body’s biggest sink for insulin-driven glucose uptake. So if hormones are falling, protein is low and she isn’t strength training, a GLP-1 can make a muscle problem worse. That’s exactly why I never use one without that foundation in place.


Why this matters with GLP-1's

Most people don't stay on these drugs forever. In a 2025 study of more than 125,000 US adults, about 65% of people without diabetes had stopped their GLP-1 within a year. Insurance changes, side effects, cost, or they hit their goal.

What happens next is the part that interests me. In a Danish randomized trial, people who lost weight on a low-calorie diet were then assigned to a year of liraglutide, supervised exercise, both, or placebo. Combining the two worked best during treatment. Then everything stopped, and researchers checked back a year later. Weight regain after stopping liraglutide alone was about 6 kg greater than after stopping exercise alone, and the group that had done both kept more of their loss than the medication-only group.


Campbell also made the case, going back as far as the Minnesota Starvation Experiment, that losing a lot of lean mass during a diet drives the intense hunger and rebound that so many women know too well. That piece is still debated, but the practical lesson holds either way. The medication is temporary for most people. The muscle and the habits are what you keep.


How I actually approach it

Nobody walks in and walks out with a GLP-1 prescription. I start with labs and health history, including a full picture of your day to day. How much do you move, and what kind of movement is it? How are you sleeping? Are you in perimenopause or postmenopause, and are you on hormone therapy? How much protein are you actually eating (most women are surprised by this one)? What does a normal Tuesday look like?

From there, it usually goes one of a few ways.

When risk is high right now. If you have a cardiometabolic profile that puts you at real near-term risk for heart disease or diabetes, we may start a low-dose GLP-1 alongside lifestyle changes from day one. Let's be honest, it's hard to get to the gym when you're carrying significant excess weight and your knees hurt. So you start with simple movement, build on whatever you're already doing, and add slowly as your body allows.


When there's room to build first. If you're dealing with insulin resistance, early fatty liver or prediabetes, but your immediate risk isn't high and you aren't strength training yet, we build first, together. More muscle, more protein, hormones addressed, sleep addressed. Then I recheck labs and reevaluate whether a GLP-1 makes sense in about three months. A lot of women don't end up needing one.

Sometimes both. Bodies don't fit neatly into categories, and neither does my care.


Everything is individualized.

When I do use a GLP-1, I go low and slow. Small doses, gradual titration, and a goal of steady weight loss rather than dramatic weeks on the scale. My reasoning comes from body composition research: in a trial of elite athletes, a slower rate of weight loss preserved lean mass better than a faster one, even with protein and training matched. I want to be upfront that no trial has tested low-dose GLP-1 strategies specifically for muscle preservation yet. It's clinical judgment built on the physiology, and I track body composition as we go.

In every case, the GLP-1 is adjunctive. It supports the primary work, it doesn't replace it.


The foundation, medication or not

Campbell described weight loss as putting your body into a catabolic state. That's great for breaking down fat, but the same environment will happily break down muscle too. The job is to drop anabolic signals into it on purpose. Here's what that looks like in my practice.


Protein, every day. There's a concept called the protein leverage hypothesis: appetite seems to track protein, so when a diet runs low in protein, we tend to keep eating until we've met our need. A GLP-1 turns appetite way down, which makes it very easy to under-eat protein without noticing. Protein paired with resistance training is what drives muscle protein synthesis, and protein also costs more energy to digest than carbs or fat and keeps you full longer. In a small study of young athletes in a steep calorie deficit, the group eating about 1.0 g/kg of protein lost more than five times as much lean mass as the group eating about 2.3 g/kg. Campbell recommends 1.6 to 2.2 g per kg per day, and for women carrying extra weight, I calculate it from goal weight rather than current weight.


Lift something. Resistance training is the strongest signal you can send muscle. Any movement helps, and even walking reduces lean mass loss during weight loss in people with obesity. But if I had to pick one thing, it's strength work. The principles don't change at midlife; the recovery, sleep and joint considerations do.


Protect your sleep. In a controlled study, people dieting on short sleep lost less fat and more lean mass than the same people dieting with adequate sleep. Sleep deprivation also blunts muscle protein synthesis. For perimenopausal women up at 3am, this one matters more than most people realize.


Creatine. For women who are training, 3 to 5 grams a day is one of the best-studied, least expensive supports for building muscle. No loading phase needed.


Hormones. A Danish randomized trial gave early postmenopausal women either a transdermal estradiol patch or a placebo patch, and everyone did 12 weeks of supervised leg training. The estradiol group roughly doubled the growth in thigh muscle size (7.9% vs 3.9% on MRI), although strength gains were similar between groups. The Menopause Society doesn't recommend hormone therapy for muscle on its own, and I don't prescribe it for that. But for a woman who is already a good candidate for hormone therapy because of symptoms or bone health, it's a meaningful bonus when the goal is also protecting muscle.


Let's recap

  • When women cut calories, some of what comes off is muscle, not just fat. That's true on a diet and on a GLP-1.

  • Muscle is where most insulin-driven glucose goes, so losing it raises the risk of insulin resistance, type 2 diabetes and heart disease over time.

  • Weight loss lowers your metabolic rate, and losing muscle makes that drop bigger, which sets up the rebound so many women know too well.

  • Losing weight without strength training and enough protein puts that muscle at risk.

  • Most women meet the bare-minimum protein RDA but fall well short of what muscle needs during weight loss and midlife.

  • A GLP-1 used on top of that foundation, low and slow, is a tool. Used instead of it, it's a bandaid.


Let's talk

If you've been quietly wondering whether a GLP-1 makes sense for you, or you're already on one and worried about what it's doing to your muscle, that's exactly the conversation we'd have in a consult. No judgment. Just your labs, your history, and a plan that fits your body.



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