Tirzepatide cuts fat mass by 35% while preserving skeletal muscle

By Vijay Kumar MalesuReviewed by Benedette Cuffari, M.Sc.Oct 2 2026

Six months of real-world treatment reveals how weight, fat mass, skeletal muscle, and metabolic health change in adults taking tirzepatide.

Study: Real-world effectiveness of 6-month tirzepatide therapy on body weight and composition in adults with overweight and obesity. Image Credit: Prostock-studio / Shutterstock.com

In a recent study published in the Journal of Diabetes and Its Complications, researchers assessed the real-world effectiveness (RWE) of tirzepatide on body composition, metabolic outcomes, and body weight in adults with overweight or obesity.

Why body composition matters in obesity treatment

Obesity is a substantial public health burden, affecting one in eight people globally. Lifestyle interventions, such as greater physical activity and caloric restriction, are central to obesity management. Yet, these approaches often have limited long-term adherence, leading to weight regain.

Tirzepatide is a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist. It can substantially reduce weight and improve metabolic outcomes. Despite the emphasis on body composition as an outcome in obesity treatment, real-world evidence on tirzepatide's impact on body composition is limited.

How researchers tracked weight and body composition in real-world care

In this study, researchers examined RWE on tirzepatide's effects on body composition, metabolic outcomes, and body weight in overweight or obese adults. Participants were adults treated at two centers in Palermo, Italy, with overweight (body mass index [BMI] ≥ 27 kg/m²) or obesity (BMI ≥ 30 kg/m²), at least one related comorbidity (prediabetes, hypertension, obstructive sleep apnea, dyslipidemia, or cardiovascular disease), and without type 2 diabetes.

Patients who became pregnant during follow-up and those who used GLP-1 receptor agonists in the past three months were excluded. Participants initiated tirzepatide at 2.5 mg once weekly, which was increased to 5 mg after 4 weeks, and followed a low-carbohydrate diet with no prescribed caloric restriction for 24 weeks. They also engaged in tailored physical activity; non-comorbid individuals under 50 years were advised to perform aerobic and resistance training.

Study participants 50 years and older or with comorbidities were encouraged to complete at least 150 minutes of moderate-intensity aerobic activity weekly. Clinical, body composition, laboratory, and anthropometric measurements were obtained at baseline, week 12, and week 24. Anthropometric measures included BMI, body weight, waist-to-height ratio (WtHR), and waist circumference (WC), whereas bioelectrical impedance analysis was used to estimate skeletal muscle mass (SMM), fat-free mass (FFM), and fat mass (FM).

Fasting plasma glucose (FPG) and fasting insulin levels were measured, in addition to insulin resistance values based on the homeostatic model assessment (HOMA-IR). The study's primary outcome was the change in body weight after 24 weeks compared to baseline. Secondary outcomes included changes in WC, BMI, metabolic markers, and body composition.

Tirzepatide users lose more fat while preserving skeletal muscle.

The study included 122 obese or overweight adults with a mean age of 44 years. Most participants were female (79.5%), obese (78%), and non-smokers (93%). About 15% of participants had dyslipidemia, 19% had hypertension, 15.6% had prediabetes, and 4% had obstructive sleep apnea. All anthropometric measures significantly decreased at 12 and 24 weeks as compared to baseline.

At 12 weeks, 86%, 41%, 12%, and 2% of participants achieved weight loss of at least 5%, 10%, 15%, and 20%, respectively. At 24 weeks, the proportions of subjects who attained the corresponding weight reduction thresholds increased to 98%, 89%, 72%, and 59%, respectively. After 24 weeks, average reductions in BMI, WC, and WtHR were 15.7%, 14.9%, and 15.2%, respectively, compared with baseline.

FM and FFM decreased significantly over time, whereas SMM remained stable. FM declined by 35.4% compared to baseline, whereas FFM decreased by 5.1%. Insulin sensitivity and glycemic control improved over time. Correlation analysis indicated that changes in BMI, body weight, and FM were positively associated with HOMA-IR and fasting insulin levels.

Conclusions

Collectively, the study examined the RWE of a 24-week tirzepatide treatment on body composition, weight, and metabolic outcomes in obese or overweight adults. Tirzepatide treatment, alongside dietary and physical activity interventions, was associated with progressive and substantial weight loss of nearly 16% from baseline. The mean weight loss was 15 kg, with an average tirzepatide dose of 5.3 mg, over 24 weeks.

Metabolic parameters and body composition also improved significantly. FM was reduced by 35%, with modest FFM loss, while SMM was relatively preserved. Reductions in FM were significantly correlated with reductions in fasting insulin and HOMA-IR.

The study’s limitations include the retrospective design and lack of a control arm, which make it difficult to separate the effects of tirzepatide from those of the accompanying diet and physical activity interventions. The analysis also included only patients who completed the 24-week follow-up, which may have influenced estimates of treatment effectiveness.

Body composition was assessed using bioelectrical impedance analysis under routine clinical conditions, and most participants were women, which may limit the generalizability of the body composition findings. Systematic data on treatment persistence and adverse events were also unavailable.

The study was conducted in one geographic area, warranting additional studies in broader, more diverse clinical populations. Further research with longer intervention and a more balanced sample is needed to assess the durability of the observed effects and their long-term impact on functional and metabolic outcomes.