Does Zepbound Cause Muscle Loss? What Body Scans Show

Zepbound® and Mounjaro® contain the same medicine, tirzepatide. Mounjaro® was approved first, for type 2 diabetes, and Zepbound® followed in 2023 for weight reduction ^[1]. What the research shows for one applies to the other.

Reading this from Britain? Zepbound is not sold in the UK, where tirzepatide is prescribed as Mounjaro. Everything on this page applies to it. We also cover what Mounjaro costs in the UK and who qualifies on the NHS separately.

Tirzepatide does not appear to single out muscle. Its prescribing information says it "lowers body weight with greater fat mass loss than lean mass loss" ^[2]. But any large weight loss takes some lean mass with it. A long-standing rule of thumb is that about a quarter of the weight lost through calorie restriction is fat-free mass, although the researchers who reviewed that rule stress it varies between people ^[3].

So the honest answer is yes: most of what you lose on Zepbound® is fat, and some of it is lean mass.

That is not the same as saying you lose that much muscle. On a DXA body scan, lean mass is everything that is not fat or bone. It includes muscle, but also water, organs and connective tissue, and none of the trials below measured muscle on its own with DXA.

The best numbers come from SURMOUNT-1, the main weight-loss trial of tirzepatide. After 72 weeks, average weight loss was 15.0% on 5 mg, 19.5% on 10 mg and 20.9% on 15 mg, compared with 3.1% on placebo ^[4].

A sub-study scanned 160 of the trial's 2,539 participants with DXA at the start and at week 72 ^[5]. DXA is a low-dose X-ray scan that measures fat, lean mass and bone separately.

Two things stand out. First, the split between fat and lean mass was about the same on tirzepatide as on placebo, even though people on tirzepatide lost four times as much weight ^[5]. People lost more lean mass on tirzepatide because they lost much more weight overall, not because a bigger share of it came from lean mass.

Second, the split was similar across groups. On tirzepatide, fat made up 74% of the weight lost in people under 50, 75% in people aged 50 to 64 and 76% in people 65 and over. It was 75% in women and 73% in men ^[5].

Mostly fat. In SURMOUNT-1, fat mass fell by about a third, while lean mass fell by about a tenth ^[5].

A second study looked inside the muscle itself. In SURPASS-3 MRI, 246 people with type 2 diabetes had MRI scans of their thigh muscles before and after 52 weeks of tirzepatide ^[6]:

• Muscle volume fell by 0.64 litres on average, broadly in line with what you would expect for the amount of weight they lost ^[6].
• Fat stored inside the muscle fell by more than expected for that weight loss ^[6].

This was a later analysis of a trial in people with diabetes, so treat it as encouraging rather than proof that muscle quality improves.

What about strength? No tirzepatide trial has measured it directly. On questionnaires, people on tirzepatide in SURMOUNT-1 reported bigger improvements in physical function than people on placebo ^[7]. A 2026 systematic review of 35 randomized trials of these medicines found that none reported objective physical function tests, such as grip strength or walking speed ^[8].

Nobody knows for sure, because no trial has compared the two medicines head to head on body composition. SURMOUNT-5, the head-to-head trial of tirzepatide and semaglutide (Wegovy®, Ozempic®), measured weight and waist size but not fat or lean mass ^[9]. People in that trial lost 20.2% of their body weight on tirzepatide and 13.7% on semaglutide over 72 weeks ^[9].

You can line up the separate body scan studies, but they involved different people:

The 2026 review in the Annals of Internal Medicine pulled together 35 trials of liraglutide, semaglutide, tirzepatide and dulaglutide. Across them, the median share of weight lost from muscle-related measures was 28.3%, and it varied widely between studies ^[8]. Losses went beyond the review's benchmarks in about two thirds of the medicine trials, and also in nearly half of the diet and lifestyle trials that produced weight loss ^[8].

The practical takeaway: don't choose a medicine based on muscle claims. Whichever one you take, protein and strength training are the parts you control. For semaglutide in detail, see does Ozempic cause muscle loss?

The body scan study found a similar fat-to-lean split at every age ^[5], but the same share can matter more for some people:

• Adults over 65. Muscle mass and strength decline with age, and strength tends to fall faster than muscle size ^[11]. Low strength is the starting point for suspecting sarcopenia, the medical condition of low muscle strength with low muscle quantity or quality ^[12]. Read more in muscle loss after 40.
• People eating very little protein. Research in people using GLP-1 medicines suggests protein intake often falls short of what a lower-calorie diet calls for ^[13].
• People with ongoing stomach side effects. In the Zepbound® trials, nausea affected 25–29% of people compared with 8% on placebo, and vomiting 8–13% compared with 2% ^[2]. Days of eating very little make protein targets hard to reach.
• People who do no strength training. Exercise programs that include resistance training have a lean-mass-preserving effect that aerobic-only programs do not ^[14].

The scale cannot tell fat from muscle, so watch these instead:

1. Strength going backwards. Lifting less, or managing fewer reps, for several weeks in a row while your weight falls is the clearest sign to act on.
2. Everyday tasks feeling harder, like climbing stairs, carrying shopping or getting up from a chair.
3. Weight dropping while your waist barely changes.

The trials used DXA scans, but you do not need one to track your progress. A study comparing consumer smart scales with DXA found their body composition estimates were not accurate enough to rely on for individuals ^[15]. If you use a smart scale, watch the trend over weeks rather than a single reading.

The simplest weekly check is your weight trend next to a log of a few lifts. For more detail, see signs you're losing muscle, not fat and are smart scales accurate?

The Zepbound® prescribing information does not list muscle pain, cramps or muscle weakness among its common side effects ^[2]. It does list fatigue, a group that includes weakness, lethargy and feeling unwell, in 5–7% of people on Zepbound® compared with 3% on placebo ^[2].

That does not mean aches never happen, only that they were not common enough in the trials to be listed. The label also warns that vomiting and diarrhea can lead to dehydration, which has caused kidney problems in some people ^[2].

Mild soreness a day or two after a new or harder workout is common. If you have new, severe or lasting muscle pain, cramps or weakness, tell your prescriber rather than training through it.

A 2025 joint advisory on nutrition for GLP-1 therapy, from four US nutrition and obesity societies, notes that the basic recommended intake is 0.8 g of protein per kg of body weight a day, and that higher targets of 1.2–1.6 g/kg a day have been proposed during active weight loss ^[16]. It also offers a simpler target of 80–120 g a day ^[16].

For example, someone weighing 90 kg (198 lb) with a BMI under 30 would land on 108–144 g a day at 1.2–1.6 g/kg.

If your BMI is 30 or above, multiplying by your full weight gives a number that is hard to reach. Our guide on how much protein to eat on Zepbound, Ozempic or Mounjaro explains which weight to use, and the free protein calculator works out a range for you. For meals that add up to it, see the 7-day GLP-1 meal plan, and the muscle loss calculator turns your own weight loss into a likely fat and lean split.

On low-appetite days:

• Eat the protein part of each meal first.
• Split your target into 3 to 5 small portions.
• Keep easy options on hand, like Greek yogurt, eggs, milk, cottage cheese, tofu or a protein shake.

The same advisory suggests strength training at least three times a week, plus at least 150 minutes of moderate aerobic exercise, for people on GLP-1 medication ^[16]. The World Health Organization's baseline for all adults is muscle-strengthening activity on 2 or more days a week ^[17].

Here is why it matters. A meta-analysis of 6 trials in older adults with obesity on calorie-restricted diets found that adding strength training, typically three times a week, reduced the loss of lean mass by 93.5% compared with diet alone, about 0.8 kg less ^[18]. Those trials involved diets, not Zepbound®, and no completed trial has yet tested strength training alongside tirzepatide.

Medicines designed to protect muscle during weight loss are also being studied. A trial combining tirzepatide with bimagrumab is still under way, with no results posted as of September 2026 ^[19].

Start with 2 short full-body sessions a week and build to 3. The free 12-week GLP-1 workout plan has home and gym versions and a printable log.

No study has shown that lean mass lost on tirzepatide is gone for good, and none has tracked what happens to it after stopping.

What trials do show about stopping is weight regain. In SURMOUNT-4, everyone took tirzepatide for 36 weeks. People then switched to placebo regained 14.0% of their body weight over the next 52 weeks, while people who stayed on tirzepatide lost a further 5.5% ^[20]. The trial did not report whether the regained weight was fat or muscle.

Strength training helps preserve lean mass across age groups ^[14], so the plan is the same on or off the medicine: keep training and keep your protein up. If you are thinking about stopping, read what happens when you stop Zepbound and talk to your prescriber first.