In adults with prediabetes, skeletal muscle tissue characteristics and metabolic measures may respond differently to lifestyle and pharmacologic interventions. In the European Radiology Experimental, a 12-week randomized controlled trial evaluated the individual and combined effects of metformin and aerobic exercise on skeletal muscle metabolism using multiparameter magnetic resonance imaging (MRI) in adults with prediabetes. The study included 42 participants (mean age 48.4 ± 13.1 years) randomized to control (n=10), metformin (n=10), exercise (n=11), or combined therapy (n=11).

Normoglycemia at study completion occurred in 90% of participants receiving combined therapy and 80% receiving exercise alone, compared with 20% receiving metformin alone and 10% of controls. Aerobic exercise significantly reduced intramuscular adipose tissue percentage (IMAT%), MRI T2 values, and apparent diffusion coefficient (ADC), and increased fractional anisotropy (FA). Metformin alone did not significantly alter these MRI-derived muscle parameters.

Combined therapy did not further change MRI parameters or blood biomarkers compared with exercise alone but uniquely reduced visceral adipose tissue (VAT) and increased muscle cross-sectional areas (MSCAs). Reduction in IMAT% was borderline greater in participants with high baseline IMAT after combined therapy (p=0.051). MRI parameters, including IMAT%, T2, and FA, correlated with fasting glucose, glucose and insulin area under the curve, and hemoglobin A1c (HbA1c).

In this randomized controlled trial, aerobic exercise was associated with measurable changes in skeletal muscle MRI parameters and glycemic outcomes in adults with prediabetes.