Schiavo Luigi, Santella Biagio, Mingo Monica, Rossetti Gianluca, Orio Marcello, Cobellis Luigi, Maurano Attilio, Iannelli Antonio, Pilone Vincenzo
Department of Medicine, Surgery and Dentistry "Scuola Medica Salernitana", University of Salerno, 84081 Baronissi, Italy.
NBFC, National Biodiversity Future Center, 90133 Palermo, Italy.
Nutrients. 2025 Mar 30;17(7):1216. doi: 10.3390/nu17071216.
Tirzepatide (TZP), a unimolecular dual agonist targeting glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptors, is a promising weight loss agent in obesity. The preservation of metabolically active fat-free mass (FFM), muscle strength (MS), and resting metabolic rate (RMR) is essential for optimizing fat mass (FM) reduction. Although TZP is typically combined with a low-calorie diet (LCD), its impact on FFM is uncertain, and studies on MS and RMR are lacking. Evidence suggests that Low-Energy Ketogenic Therapy (LEKT) may reduce FM while preserving FFM, MS, and RMR. Therefore, this study aimed to compare the effects of an LEKT and an LCD, both combined with TZP, on body weight (BW), FM, FFM, MS, and RMR in patients with obesity. We prospectively compared the effects of TZP combined with either an LCD or LEKT in 60 patients with obesity (n = 30 per group) over 12 weeks. BW, FM, FFM, MS, and RMR were measured at baseline and after 12 weeks. Clinical parameters, an assessment of dietary compliance, and side effects were also evaluated. At 12-week follow-up, both groups showed a significant BW reduction from baseline (TZP+LEKT, = 0.0289; TZP+LCD, = 0.0278), with no significant intergroup difference ( = 0.665). Similarly, FM decreased significantly in both cohorts (TZP+LEKT, < 0.001; TZP+LCD, = 0.0185), with the TZP+LEKT group achieving a greater FM loss ( = 0.042). However, the TZP+LCD group exhibited significant declines from baseline in FFM ( = 0.0284), MS ( = 0.0341), and RMR ( < 0.001), whereas we did not observe any significant changes in FFM ( = 0.487), MS ( = 0.691), and RMR ( = 0.263) in the TZP+LEKT group. Intergroup direct comparisons confirmed that the TZP+LCD group experienced significantly greater reductions in FFM ( = 0.0388), MS ( = 0.046), and RMR ( = 0.019). Based on the findings of these preliminary data, we are able to support the hypothesis that TZP+LEKT seems to be superior to TZP+LCD in promoting FM reduction while preserving FFM, MS, and RMR in patients with obesity.
替尔泊肽（TZP）是一种靶向葡萄糖依赖性促胰岛素多肽和胰高血糖素样肽-1受体的单分子双激动剂，是一种很有前景的肥胖症减肥药物。保留代谢活跃的去脂体重（FFM）、肌肉力量（MS）和静息代谢率（RMR）对于优化脂肪量（FM）减少至关重要。尽管TZP通常与低热量饮食（LCD）联合使用，但其对FFM的影响尚不确定，且缺乏关于MS和RMR的研究。有证据表明，低能量生酮疗法（LEKT）可能在减少FM的同时保留FFM、MS和RMR。因此，本研究旨在比较LEKT和LCD联合TZP对肥胖患者体重（BW）、FM、FFM、MS和RMR的影响。我们前瞻性地比较了TZP联合LCD或LEKT对60例肥胖患者（每组n = 30）12周的影响。在基线和12周后测量BW、FM、FFM、MS和RMR。还评估了临床参数、饮食依从性评估和副作用。在12周随访时，两组的BW均较基线显著降低（TZP + LEKT， = 0.0289；TZP + LCD， = 0.0278），组间无显著差异（ = 0.665）。同样，两个队列中的FM均显著降低（TZP + LEKT， < 0.001；TZP + LCD， = 0.0185），TZP + LEKT组的FM损失更大（ = 0.042）。然而，TZP + LCD组的FFM（ = 0.0284）、MS（ = 0.0341）和RMR（ < 0.001）较基线显著下降，而我们未观察到TZP + LEKT组的FFM（ = 0.487）、MS（ = 0.691）和RMR（ = 0.263）有任何显著变化。组间直接比较证实，TZP + LCD组的FFM（ = 0.0388）、MS（ = 0.046）和RMR（ = 0.019）下降幅度明显更大。基于这些初步数据的结果，我们能够支持这样的假设，即TZP + LEKT在促进肥胖患者FM减少的同时保留FFM、MS和RMR方面似乎优于TZP + LCD。
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