Sarcopenic obesity and weight loss-induced muscle mass loss

Abstract

Purpose of review: Sarcopenic obesity is a clinical condition characterized by the coexistence of excess adiposity and impaired muscle function, associated with heightened cardiometabolic risk and frailty. The emergence of new incretin-based obesity management medications (OMMs), which allow unprecedented weight loss, has raised concerns regarding weight loss-induced fat-free mass (FFM) reduction, including skeletal muscle mass (SMM). This review examines recent findings on the prevalence, diagnosis, and implications of sarcopenic obesity, explores the effects of weight-loss interventions on body composition and their impact on health, and discusses strategies to preserve muscle mass.

Recent findings: Weight loss induced by incretin-based OMMs results in a variable but significant reduction in FFM. The extent to which this loss affects SMM and function remains uncertain. Nutritional strategies, particularly adequate protein intake, and structured exercise interventions, especially resistance training, play a key role in mitigating FFM loss. Digital health interventions and telemedicine-based exercise programs offer promising approaches for maintaining muscle health during weight loss.

Summary: The clinical significance of FFM loss during weight reduction remains debated. Future research should refine sarcopenic obesity diagnostic criteria, assess the long-term impact of FFM/SMM reduction during intentional weight loss, and evaluate interventions that optimize body composition while preserving functional health.

Keywords: GLP-1 receptor agonists; fat-free mass; muscle strength; sarcopenic obesity; weight loss.

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FIGURE 1

Screening, diagnosis, and staging of SO is a sequential process [15]. Screening requires the presence of elevated BMI or waist circumference (ethnicity-specific cut-offs) AND indicators of sarcopenia, such as clinical symptoms, risk factors, or validated questionnaires. Diagnosis is confirmed only if both impaired muscle function and increased fat mass + reduced muscle mass are present. Only if muscle function is impaired, DXA (preferred) or BIA (alternative) is used to evaluate body composition. Staging is performed once SO is diagnosed. ALM/W, appendicular lean mass adjusted to body weight; BIA, bioelectrical impedance analysis; BMI, body mass index; DXA, dual X-ray absorptiometry; FM, fat mass; SMM/W, total skeletal muscle mass adjusted by weight; SO, sarcopenic obesity; WC, waist circumference. Created in BioRender. Conte, C. (2025) https://BioRender.com/j35q358.

FIGURE 2

Schematic representation of the difference between measurements at the molecular and anatomical body composition levels. FFM and FM consist of all nonfat (water, protein, mineral, residual component) and fat molecules in the body, respectively, regardless of their location. Skeletal muscle and adipose tissue are anatomically defined. Skeletal muscle predominantly includes fat-free molecules (water, protein, minerals, glycogen, etc.), but also a small amount of lipids. Adipose tissue predominantly includes fatty molecules, but it also includes a small amount of fat-free molecules (water, protein). Data and data representation are for illustrative purposes, and are from [6^▪]. 3DO, three-dimensional optical imaging; ADP, air displacement plethysmography; BIA, bioelectrical impedance analysis; BIS, bioimpedance spectroscopy; CT, computed tomography; DXA, dual-energy x-ray absorptiometry; FM, fat mass; FFM, fat-free mass; SKF, skinfold thickness; US, ultrasonography; UWW, underwater weighing. Created in BioRender. Conte, C. (2025) https://BioRender.com/m78t115.

FIGURE 3

Changes in lean mass and strength with aging (grey, annualized rates) and after ∼ 7% weight loss achieved with calorie restriction, aerobic exercise, or both in men and women with overweight (green). Leg lean mass was measured by DXA. Leg strength was measured by isokinetic knee extensor strength at 60°/s. Approximate relative changes were derived from group-level means or medians and are reported for illustrative purposes only. Data from [71] and [72].

FIGURE 4

Schematic representation of the attenuation of weight loss-induced reduction in FFM by dietary protein and exercise. Data and data representation are for illustrative purposes. Created in BioRender. Conte, C. (2025) https://BioRender.com/b03c093.