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Background: Circuit training is an exercise mode, that may include both endurance and resistance components. There are premises that a combination of these two modalities brings additional benefits, particularly in improving insulin sensitivity. The retinol-binding protein 4 (RBP4) may inhibit signaling from insulin metabolic pathways in skeletal muscles, thus developing insulin resistance. This study aimed to evaluate whether moderate intensity circuit training combining strength and endurance exercise induces changes in tissue insulin sensitivity, carbohydrate and lipid metabolism, and serum RBP4 levels in insulin-resistant women., Methods: In this clinical controlled trial women diagnosed with insulin-resistance were randomly divided into two groups. The training group (T) performed circuit training combining strength (50%-80%1RM) and endurance (50%-75%HRR) exercise on five weight and two cardio machines, for 33 minutes, three times per week, for 3 months. Women from the control non-training group (NT) did not change their previous physical activity. At the beginning of the study and after the intervention period, a one-repetition maximum, body mass, and composition, resting heart rate (HR), blood pressure, glucose, insulin, blood lipids, thyroid-stimulating hormone (TSH), insulin-like growth factor-1 (IGF-1), RBP4, and insulin resistance (HOMA-IR) were measured. The results of 27 patients were analyzed using a two-way repeated measures ANOVA., Results: Significant differences in the pattern of change over time between the groups for resting HR (p < 0.010) and total lean mass (p < 0.039) were found. No differences in HOMA-IR, and RBP4 were observed post-study compared to pre-study in the T group. A significant correlation between RBP4 and TSH concentration was found., Conclusion: Twelve-week circuit training combining strength and endurance exercise has minor effects on HOMA-IR, glucose and lipid metabolism, IGF-1, TSH, and RBP4. Although moderate-intensity circuit training is considered safe, its effectiveness in patients with overweight and mild obesity may be insufficient to reduce insulin resistance., Trial Registration: ClinicalTrials.gov: NCT04528693, registered August 23, 2020., Competing Interests: All the authors declare that they have no competing interests., (© 2024 Ratajczak et al.)