Background Tirzepatide, a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist, has demonstrated substantial efficacy in reducing body weight and improving glycemic control in randomized trials; however, real-world data on its long-term effects remain limited. Our objective was to evaluate the one-year effects of tirzepatide on body composition, metabolic parameters, inflammation, and sleep-related outcomes in a real-world setting. Methods In this prospective study, 164 consecutive adult participants receiving tirzepatide in routine clinical practice were followed longitudinally. Anthropometric measurements, bioelectrical impedance-derived body composition indices, glycemic markers, inflammatory and biochemical parameters, and sleep-related indices were assessed at baseline and follow-up. Changes (D variables) were calculated as follow-up minus baseline values. Statistical analyses included descriptive statistics, paired comparisons, and correlation analyses. Results Tirzepatide treatment was associated with significant weight reduction (change in body weight (DWeight) -8.66 ± 8.02 kg), primarily driven by decreases in fat mass (change in fat mass (DFM) -11.34 ± 10.86 kg) and waist circumference (change in waist circumference (DWC) -10.11 ± 10.10), with relative preservation of lean mass (change in fat-free mass (DFFM) 0.87 ± 14.56 kg). Improvements were observed in glycemic control (change in glycated hemoglobin (DHbA1c) -0.59 ± 0.56%) and insulin resistance (change in homeostasis model assessment of insulin resistance (DHOMA-IR) -0.52 ± 0.29), along with reductions in inflammatory markers (change in C-reactive protein (DCRP) -1.48 ± 2.39 mg/L) and liver enzymes (change in aspartate aminotransferase (DAST) and alanine aminotransferase (DALT)). Sleep-disordered breathing improved, with a reduction in apnea-hypopnea index (change in apnea-hypopnea index (DAHI) -6.64 ± 6.63 events/h). Sex-specific differences were observed, with greater FM reduction in females and greater improvement in IR and sleep apnea indices in males. Conclusions In a real-world setting, tirzepatide demonstrates sustained benefits across adiposity, metabolic function, inflammation, and sleep outcomes over one year, with preservation of lean mass. These findings support its role as a comprehensive metabolic therapy.
