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Losing muscle on Mounjaro or Wegovy? What's happening and what helps

By Dr Aminata Kanu, PhD, protein biochemist and strength coach · Updated November 2026

GLP-1 medications such as Mounjaro (tirzepatide) and Wegovy (semaglutide) work. Most women lose a meaningful amount of weight. But not all of that weight is fat, and the part that isn't matters more than most people are told.

How much of the weight lost is muscle?

The big trials scanned some participants' bodies to see what kind of weight they lost. In the main semaglutide trial, lean mass made up roughly two fifths of the weight lost. In the main tirzepatide trial it was closer to a quarter.

Lean mass isn't only muscle. It also includes water and organs, so these figures overstate muscle loss a little. Even so, a woman who loses 15 kg could lose several kilos of muscle along the way, and muscle is far harder to put back than fat is to lose.

Why it matters more after 40

From midlife onwards we lose muscle slowly anyway, and the menopause speeds that up. Older muscle also responds less to protein than younger muscle, which scientists call anabolic resistance. Put a large weight loss on top of that and the muscle you lose may not come back on its own.

Muscle isn't about how you look. It clears much of the sugar from your meals, it keeps you steady on your feet and it makes everyday life easier, from carrying shopping to getting up off the floor. It's also part of what helps you keep the weight off if your treatment changes.

You can't feel it going

The scale only tells you that you're lighter. It can't tell you what you lost. A meal that doesn't contain enough protein to trigger muscle building feels exactly the same as one that does. That's why it's worth measuring strength as well as weight.

Two simple tests work well at home. The 30-second sit-to-stand counts how many times you can stand up from a chair in half a minute. Grip strength needs a hand dynamometer. Neither is perfect, but both tell you whether you're getting stronger or weaker, which the scale never will.

The two things that protect your muscle

There's no supplement or trick here. The evidence keeps pointing to the same two habits.

1. Enough protein at each meal, not just across the day. Muscle building switches on when a meal contains enough of the amino acid leucine, roughly 2.5 grams for most women over 40. That usually means around 30 grams of good-quality protein at a meal. Spreading it across three meals works better than one large protein dinner.
2. Lifting that's genuinely hard. In a trial of older adults losing weight, those who added resistance training kept noticeably more lean mass than those who only did aerobic exercise. What counts is effort, not time. A set counts when the last few reps are hard, with one to three left in the tank.

When appetite makes it hard

The same medication that helps you lose weight can make eating enough protein difficult. Small, protein-first meals help, as do soft and liquid options like skyr, eggs, cottage cheese or a protein shake. If you're struggling to eat or drink, or you feel unwell, speak to your prescriber.

The short version

• Some of the weight lost on GLP-1 medication is lean mass, and after 40 it's harder to regain.
• Measure strength, not only weight.
• Aim for enough protein at each meal and lift hard enough to count.

Sources

1. Wilding JPH et al. Once-weekly semaglutide in adults with overweight or obesity (STEP 1). New England Journal of Medicine, 2021.
2. Jastreboff AM et al. Tirzepatide once weekly for the treatment of obesity (SURMOUNT-1). New England Journal of Medicine, 2022.
3. Villareal DT et al. Aerobic or resistance exercise, or both, in dieting obese older adults. New England Journal of Medicine, 2017.
4. Moore DR et al. Protein ingestion to stimulate myofibrillar protein synthesis requires greater relative protein intakes in healthy older versus younger men. Journals of Gerontology, 2015.

This article is education, not medical advice. Talk to your GP or prescriber about your own treatment.