One of the most common questions we hear from patients on semaglutide or tirzepatide: “Am I losing muscle along with the fat, and is there anything I should be taking?” Here's what the evidence actually supports — including where creatine fits in.
Why This Question Matters
GLP-1 medications work in part by sharply reducing appetite — which means most people eat significantly less overall, including less protein, unless they actively correct for it. Body composition sub-studies from the major GLP-1 trials have found that roughly a quarter to as much as 40% of total weight lost on these medications can come from lean mass (muscle, not just fat), depending on the study and how lean mass was measured.
Some of that lean-mass loss is expected and even normal with any significant weight loss — a smaller body needs less muscle to move it around. But losing more muscle than necessary can lower resting metabolic rate, reduce strength and functional capacity (especially in older adults), and make it harder to keep weight off long-term. That's why the question of "what should I be taking or doing" has become such a common one.
What the Evidence Actually Supports
Importantly, there's no supplement that has been directly tested and proven, in large controlled trials, to preserve muscle specifically in people taking GLP-1s. Most of what we know is extrapolated from two places: general weight-loss and aging-muscle research, and a smaller but growing set of studies looking at resistance training and protein intake alongside GLP-1 therapy.
The two interventions with the strongest evidence behind them aren't supplements at all — they're resistance training (lifting weights or doing bodyweight strength work at least twice a week) and adequate protein intake. Everything else, including creatine, is a supporting player.
Protein First, Then Creatine
Because appetite drops so much on these medications, hitting a protein target becomes the single most impactful nutrition change most people can make. A common clinical target is around 1.2–1.6 grams of protein per kilogram of body weight per day, spread across meals — though your own target should be set with your care team based on kidney function and other health factors.
Is creatine a good option?
Creatine monohydrate is one of the most studied supplements in sports medicine, with a strong track record of helping preserve and build muscle when paired with resistance training — particularly during calorie restriction, where it's been shown in general weight-loss research to help offset lean-mass loss. Direct trials in GLP-1 users specifically are still limited, but the underlying mechanism (helping muscle cells maintain energy and recover from strength training) applies just as well here. A typical studied dose is 3–5 grams per day, taken consistently. It's inexpensive, has a long safety record in healthy adults, and doesn't require a "loading phase" to work.
Other Supplements Worth Discussing With Your Doctor
- A multivitamin — with appetite this suppressed, it's easy to fall short on micronutrients across the board, especially early on.
- Vitamin B12 — worth checking, particularly if nausea is limiting the variety of food you're eating.
- Vitamin D and calcium — relevant for bone health during any significant weight loss, since bone density can decline alongside fat and muscle mass.
- Fiber and electrolytes — not for muscle preservation, but genuinely useful for the constipation, dehydration, and low-appetite side effects many people experience.
A note on kidney function
Creatine is generally considered safe for people with healthy kidneys, but it does raise creatinine levels as a normal byproduct of use, which can confuse routine kidney-function bloodwork. If you have diabetes, existing kidney disease, or are on other medications that affect the kidneys, talk to your doctor before starting — and make sure they know you're taking it before your next lab draw.
A Few Things Worth Keeping in Mind
- Supplements are not a substitute for resistance training. The strongest, best-supported way to preserve muscle during weight loss is strength training two or more times a week — creatine amplifies that effect, it doesn't replace it.
- Supplements aren't FDA-regulated the way medications are. Quality and purity vary by brand; look for third-party testing (NSF Certified for Sport or USP-verified) when possible.
- Not everyone needs every supplement on this list. Your actual needs depend on your labs, your diet, your kidney function, and how well you're tolerating the medication itself.
- This is a fast-evolving area. Larger, GLP-1-specific trials on muscle preservation strategies are underway, and guidance may become more specific as that data matures.
What You Can Actually Do
- Prioritize protein at every meal, even in small amounts — it's the highest-leverage change you can make on a reduced appetite.
- Add resistance training if you aren't already doing it — two sessions a week is a reasonable starting goal, and it doesn't have to mean a gym membership.
- Consider creatine monohydrate, 3–5 grams daily, especially if you're strength training — but check in with your doctor first if you have kidney or diabetes concerns.
- Ask your doctor about labs — a basic metabolic panel and vitamin levels can catch gaps before they become problems.
The bottom line: Muscle loss is a real consideration on GLP-1 medications, and protein intake plus resistance training remain the best-supported ways to protect it. Creatine monohydrate is a reasonable, low-risk addition with good general evidence for muscle preservation during weight loss — but it works alongside those fundamentals, not instead of them, and it's worth a quick check-in with your doctor first, especially if kidney health is a factor for you.
Partnering in your care,
Dr. Kenji Taylor, MD
Torii Health & Iris Dental and Medical