The 30-second summary
- A clinic study from Palermo, Italy, published on 25 September 2026 in the Journal of Diabetes and Its Complications, followed 122 adults on tirzepatide (Mounjaro, Zepbound) for 24 weeks.
- Everyone also followed a standardised low-carbohydrate diet and a tailored physical activity plan.
- Weight fell from 95 kg to 80 kg, fat mass by 35% and fat-free mass by 5%. Skeletal muscle mass did not change significantly.
- There was no comparison group, so the study cannot separate the drug from the diet and activity.
What did the study do?
Researchers at the University of Palermo and Candela Hospital looked back at 122 adults with overweight or obesity and at least one related condition, none with diabetes. They were 80% women, with an average age of 44.
All of them started tirzepatide at 2.5 mg once a week, moving to 5 mg after four weeks. After that, doses were adjusted person by person. The average dose at the end was 5.32 mg, low compared with the 10 mg and 15 mg doses many people reach.
Alongside the medicine, everyone followed a standardised low-carbohydrate diet and a physical activity plan tailored to them. The published abstract does not give the details of either.
Body composition was measured with bioelectrical impedance analysis at the start and after 24 weeks.
What did it find?
| Measure | Start | 24 weeks |
|---|---|---|
| Weight | 95 kg | 80 kg |
| BMI | 35 | 29 |
| Waist | 109 cm | 92 cm |
| Waist-to-height ratio | 0.66 | 0.56 |
| HbA1c | 5.5% | 5.2% |
| Insulin resistance (HOMA-IR) | 4.2 | 2.5 |
Fat mass fell by 35%. Fat-free mass, which includes muscle, water, organs and bone, fell by 5%. Skeletal muscle mass, the part you use to move, did not change significantly.
People whose fat mass fell most also saw the biggest falls in insulin and insulin resistance.
The overall weight loss was about 16% in 24 weeks. The authors note that this matches what SURMOUNT-1 reported after 72 weeks, and suggest a full clinical approach in practice may do better than trials. For context, SURMOUNT-1 reported 15.0% at 72 weeks on 5 mg and 20.9% on 15 mg (Jastreboff et al., 2022). The comparison is between very different settings, so it is a talking point, not a result.
Why does the fat-to-muscle split matter?
When people lose a lot of weight, some of it is always lean tissue. The question is how much, and it varies from person to person.
Muscle carries your strength and helps with blood sugar control. Losing mostly fat, and holding muscle, is what makes the new weight easier to keep and to live in. That is why studies like this one look past the scale.
What are the limits?
This is an encouraging result from a weak design, and both halves matter.
- No control group. Without people on tirzepatide alone, or on the diet alone, nobody can say which part did what.
- Retrospective. The data were collected in routine care and analysed afterwards.
- Bioelectrical impedance. It is less precise than DXA or MRI, and shifts in body water during weight loss can affect its estimates of muscle.
- The diet is not described in the abstract, so "low-carbohydrate" could mean many things.
- One clinic, 24 weeks. Longer follow-up and other populations may look different.
- A low average dose. The average final dose was 5.32 mg, so results at 10 mg or 15 mg may differ.
It also sits beside a recent Madrid study of 388 people on GLP-1 medicines with lifestyle advice, which found mostly fat loss and a modest fall in muscle over six months. Two clinic studies pointing the same way is not proof, but it is a pattern.
What does it mean if you take tirzepatide?
The useful message is not "go low-carb". It is that the people in this study were not taking the drug on its own. They had a set way of eating and a plan for moving, and the weight they lost was mostly fat.
You can build the same structure around whatever way of eating suits you:
- A protein target at every meal. Protein is what tells your body to keep muscle while fat comes off. Protein on a GLP-1 explains how much and how to spread it across the day.
- Planned meals, not leftovers of appetite. A small appetite tends to pick the easiest food, not the most useful.
- Resistance work twice a week. It is the strongest signal you can give muscle to stay. Keeping muscle on a GLP-1 covers where to start.
If you have kidney disease, diabetes on insulin, or another condition that affects what you can eat, talk to your prescriber or a dietitian before changing your diet.
Sources
- Brancato D, Maggio V, Vaccaro F, et al. Real-world effectiveness of 6-month tirzepatide therapy on body weight and composition in adults with overweight and obesity. J Diabetes Complications 2026. PubMed
- Jastreboff AM, Aronne LJ, Ahmad NN, et al. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med 2022. PubMed