Effect of short-term tirzepatide treatment on mean platelet volume in patients with obesity: a retrospective controlled study

OBJECTIVE: Obesity is associated with chronic low-grade inflammation, increased cardiovascular risk, and alterations in platelet indices [1-5]. Mean platelet volume (MPV) is an easily obtainable surrogate marker that has been linked to platelet activation and inflammatory burden [4, 6-8]. This study evaluated whether short-term tirzepatide therapy was associated with changes in MPV in patients with obesity compared with an untreated control group. METHODS: In this retrospective controlled study, 60 adults with obesity were included: 30 patients who received tirzepatide for two months and 30 untreated controls followed during the same period. Demographic data, body mass index (BMI), and MPV values at baseline and at two months were obtained from electronic medical records. Within-group changes were assessed using paired tests. Between-group comparisons of change scores were performed, and multivariable linear regression was used to evaluate the association between tirzepatide treatment and MPV change after adjustment for baseline BMI, baseline MPV, age, and sex. RESULTS: Baseline BMI and MPV were comparable between the tirzepatide and control groups (BMI: 40.22 ± 4.10 vs. 39.86 ± 3.49 kg/m², p = 0.713; MPV: 10.65 ± 0.87 vs. 10.18 ± 1.30 fL, p = 0.105). In the tirzepatide group, BMI decreased significantly from 40.22 ± 4.10 to 36.30 ± 3.90 kg/m² (mean change - 3.92 kg/m², 95% CI -5.93 to -1.91; p < 0.001), and MPV decreased from 10.65 ± 0.87 to 9.72 ± 1.17 fL (mean change - 0.94 fL, 95% CI -1.44 to -0.44; p < 0.001). The between-group difference in MPV change was significant (mean difference - 1.35 fL, 95% CI -2.22 to -0.48; p = 0.003). In adjusted regression, tirzepatide treatment remained independently associated with greater MPV reduction (beta - 1.13, 95% CI -1.97 to -0.29; p = 0.009). CONCLUSION: Short-term tirzepatide treatment was associated with significant reductions in BMI and MPV compared with untreated controls. Because of the retrospective design, short follow-up, and absence of direct inflammatory and platelet-function biomarkers, these findings should be interpreted as hypothesis-generating rather than conclusive evidence of a direct platelet-modulating effect.