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

Abstract

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.

Introduction

Obesity is a major global health problem and is strongly associated with cardiometabolic morbidity and mortality [1–3]. Beyond excess adiposity, obesity is characterized by chronic low-grade inflammation, insulin resistance, endothelial dysfunction, and a prothrombotic milieu, all of which may contribute to cardiovascular risk [2–4].

Adipose tissue functions as an active endocrine and immune organ. Adipocyte dysfunction and macrophage infiltration promote cytokine release and metabolic inflammation, which may influence vascular biology and platelet reactivity [2, 4, 5]. Recent work has further emphasized the importance of immune-metabolic pathways in obesity-related inflammation, including macrophage metabolic reprogramming and glutamine metabolism [5].

Mean platelet volume (MPV) is a simple and widely available hematological parameter reflecting platelet size [6]. Larger platelets are generally considered more reactive; therefore, MPV has been used as a surrogate marker of platelet activation and inflammatory status [6–9]. However, MPV is influenced by pre-analytical, hematological, and metabolic factors and should not be interpreted as a direct measure of platelet function [6, 10].

Tirzepatide is a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist with established effects on weight reduction and metabolic improvement [11, 12]. In addition to weight loss, incretin-based therapies may influence inflammatory pathways, endothelial function, and cardiovascular risk [13, 14]; however, data regarding the effect of tirzepatide on platelet indices such as MPV remain limited.

Given the links among obesity, inflammation, platelet indices, and cardiovascular risk [2–4, 6–9], evaluating MPV changes after tirzepatide therapy may provide preliminary insight into possible hematological and inflammatory changes during early treatment. Therefore, this retrospective controlled study investigated changes in MPV after two months of tirzepatide therapy in patients with obesity compared with untreated controls.

Materials and methods

Study design and participants

This retrospective observational controlled study was conducted at Abat Medical Center. Adult patients with obesity who received tirzepatide therapy and had available baseline and two-month follow-up laboratory and anthropometric data were included in the tirzepatide group. The control group consisted of adults with obesity who were followed during the same period but did not receive pharmacological anti-obesity treatment.

Patients aged 18 years or older with BMI ≥ 30 kg/m² were eligible. Exclusion criteria were active infection, acute or chronic inflammatory disease, known hematological disease, malignancy, liver or kidney disease, and use of antiplatelet or anticoagulant therapy. Consecutive eligible patients were enrolled between February 1, 2026 and April 1, 2026. When available in the medical records, concomitant medications and clinical conditions that could affect platelet indices were reviewed. Because of the retrospective nature of the study, unmeasured factors such as smoking, alcohol intake, intermittent non-steroidal anti-inflammatory drug use, diet, and physical activity could not be fully controlled and are acknowledged as limitations.

Treatment and control group management

Tirzepatide treatment was initiated at 2.5 mg once weekly and titrated according to tolerability and clinical response in routine clinical practice. During the two-month treatment period, patients received standard lifestyle recommendations, including a calorie-restricted diet and encouragement to increase physical activity. The control group did not receive pharmacological anti-obesity treatment during the study period but received the same standard lifestyle recommendations regarding diet and physical activity.

Data collection

Age, sex, BMI, and MPV values were retrospectively extracted from electronic medical records. Baseline values were defined as measurements obtained immediately before tirzepatide initiation in the treatment group and at the corresponding baseline visit in the control group. Follow-up values were defined as measurements obtained at approximately two months. BMI was calculated as weight in kilograms divided by height in meters squared (kg/m²).

Ethical considerations

The study protocol was reviewed and approved by the relevant ethics committee (approval date: 22.01.2026; approval number: 43742). The study was conducted in accordance with the principles of the Declaration of Helsinki. Because of the retrospective design and use of anonymized data, the requirement for written informed consent was waived by the ethics committee.

Statistical analysis

Statistical analyses were performed using SPSS and Python/statistical software. Continuous variables were expressed as mean ± standard deviation. Categorical variables were expressed as number and percentage. Baseline between-group comparisons were performed using independent-samples t tests for continuous variables and chi-square tests for categorical variables. Within-group pre-post comparisons were performed using paired t tests. Change scores were calculated as two-month value minus baseline value. Between-group differences in change scores were assessed using independent-samples t tests, with 95% confidence intervals (CIs).

To address potential confounding, multivariable linear regression was performed with MPV change as the dependent variable. Tirzepatide treatment group, baseline BMI, baseline MPV, age, and sex were included as covariates. A second exploratory model additionally included BMI change. The association between BMI change and MPV change within the tirzepatide group was examined using Pearson correlation. Post-hoc power was estimated based on the observed between-group effect size for MPV change. A two-sided p value < 0.05 was considered statistically significant; p values reported as 0.000 were corrected to p < 0.001.

Results

A total of 60 patients with obesity were included: 30 in the tirzepatide group and 30 in the untreated control group. Baseline age, sex distribution, BMI, and MPV were not significantly different between groups. Mean age was 41.80 ± 9.06 years in the tirzepatide group and 41.30 ± 7.46 years in the control group (p = 0.816). The proportion of men was 60.0% in the tirzepatide group and 50.0% in the control group (p = 0.436). Baseline BMI was 40.22 ± 4.10 kg/m² in the tirzepatide group and 39.86 ± 3.49 kg/m² in the control group (p = 0.713). Baseline MPV was also comparable (10.65 ± 0.87 vs. 10.18 ± 1.30 fL; p = 0.105) (Table 1).

Table 1.

Baseline demographic and clinical characteristics

Variable	Tirzepatide (n = 30)	Control (n = 30)	p value
Age (years)	41.80 ± 9.06	41.30 ± 7.46	0.816
Sex (M/F), n (%)	18 (60.0%) / 12 (40.0%)	15 (50.0%) / 15 (50.0%)	0.436
Baseline BMI (kg/m²)	40.22 ± 4.10	39.86 ± 3.49	0.713
Baseline MPV (fL)	10.65 ± 0.87	10.18 ± 1.30	0.105

Values are presented as mean ± standard deviation unless otherwise stated. Between-group comparisons were performed using independent-samples t tests or chi-square tests, as appropriate. BMI: body mass index; MPV: mean platelet volume

After two months, BMI decreased significantly in the tirzepatide group 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). In the control group, BMI remained stable (39.86 ± 3.49 to 39.88 ± 3.58 kg/m²; mean change 0.02 kg/m², 95% CI -0.32 to 0.36; p = 0.911). The between-group difference in BMI change was significant (mean difference − 3.94 kg/m², 95% CI -5.97 to -1.91; p < 0.001).

MPV decreased significantly in the tirzepatide group 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). In contrast, the control group showed no statistically significant within-group change in MPV (10.18 ± 1.30 to 10.60 ± 1.96 fL; mean change 0.41 fL, 95% CI -0.31 to 1.14; p = 0.254). The between-group difference in MPV change was significant (mean difference − 1.35 fL, 95% CI -2.22 to -0.48; p = 0.003) (Table 2; Fig. 1).

Table 2.

Changes in BMI and MPV over two months

Variable	Group	Baseline	2 months	Change	95% CI for change	Within-group p	Between-group p for change
BMI (kg/m²)	Tirzepatide	40.22 ± 4.10	36.30 ± 3.90	-3.92	-5.93 to -1.91	< 0.001	< 0.001
BMI (kg/m²)	Control	39.86 ± 3.49	39.88 ± 3.58	0.02	-0.32 to 0.36	0.911
MPV (fL)	Tirzepatide	10.65 ± 0.87	9.72 ± 1.17	-0.94	-1.44 to -0.44	< 0.001	0.003
MPV (fL)	Control	10.18 ± 1.30	10.60 ± 1.96	0.41	-0.31 to 1.14	0.254

Change was calculated as two-month value minus baseline value. Negative values indicate reduction. Between-group p values compare change scores between the tirzepatide and control groups

Fig. 1.

Mean MPV change over two months in the tirzepatide and control groups. Error bars represent 95% confidence intervals. The between-group difference in MPV change was − 1.35 fL (95% CI -2.22 to -0.48; p = 0.003)

Within the tirzepatide group, BMI change was not significantly correlated with MPV change (Pearson r=-0.18, p = 0.336; Spearman rho=-0.27, p = 0.156). In multivariable regression adjusted for baseline BMI, baseline MPV, age, and sex, tirzepatide treatment remained independently associated with greater MPV reduction (beta − 1.13, 95% CI -1.97 to -0.29; p = 0.009). This association remained significant after additional adjustment for BMI change (beta − 1.18, 95% CI -2.16 to -0.19; p = 0.020). Post-hoc power for detecting the observed between-group difference in MPV change was estimated at 0.87.

Multivariable linear regression analysis demonstrated that tirzepatide treatment remained independently associated with MPV reduction after adjustment for baseline BMI, baseline MPV, age and sex (Table 3).

Table 3.

Multivariable linear regression for MPV change

Variable	Beta	95% CI	p value	Model
Tirzepatide treatment	-1.13	-1.97 to -0.29	0.009	Adjusted for baseline BMI, baseline MPV, age, and sex
Baseline BMI	0.03	-0.08 to 0.14	0.539
Baseline MPV	-0.58	-0.95 to -0.20	0.003

Dependent variable: MPV change (two-month MPV minus baseline MPV). Negative beta values indicate greater MPV reduction

Discussion

In this retrospective controlled study, two months of tirzepatide treatment was associated with significant reductions in both BMI and MPV in patients with obesity. Importantly, baseline BMI and MPV were comparable between the treatment and control groups, and the between-group comparison of change scores demonstrated a significantly greater MPV reduction in the tirzepatide group. In adjusted regression analyses, tirzepatide treatment remained associated with MPV reduction after controlling for baseline BMI, baseline MPV, age, and sex.

These findings should be interpreted carefully. MPV is an indirect surrogate marker and cannot establish platelet activation by itself [6, 10]. Platelet function is influenced by multiple factors, including blood sampling conditions, measurement timing, hematologic variables, inflammatory burden, medications, smoking, and metabolic status. Therefore, the present findings support an association between tirzepatide therapy and lower MPV values, but they do not prove a direct causal effect of tirzepatide on platelet activation.

Obesity-related inflammation provides a biologically plausible context for these observations [2, 4, 15]. Adipose tissue dysfunction, macrophage infiltration, cytokine release, insulin resistance, and endothelial dysfunction may contribute to a proinflammatory and prothrombotic state [2–4]. Recent experimental and translational studies have highlighted mechanisms linking immune metabolism, inflammation, and platelet biology [5, 16]. For example, glutamine metabolism in macrophages has been proposed as a relevant pathway in obesity- and type 2 diabetes-associated inflammation [5], and recent platelet research has identified NR4A1 as a regulator of platelet activation and thrombus formation [16].

In the present study, MPV reduction was not significantly correlated with BMI reduction within the tirzepatide group. In addition, the association between tirzepatide treatment and MPV change remained significant after adjustment for BMI change in an exploratory model. These findings suggest that the observed MPV reduction may not be explained solely by the magnitude of weight loss. Nevertheless, because inflammatory biomarkers such as CRP, interleukin-6, and other platelet-function tests were not available, weight-independent mechanisms remain speculative [5, 6, 16].

The current findings are consistent with the broader cardiometabolic effects of incretin-based therapies. Tirzepatide produces substantial weight loss and metabolic improvement, while GLP-1 receptor agonist-based therapies have shown cardiovascular benefit in large clinical trials [13, 14]. Whether changes in platelet indices contribute to these benefits requires further investigation using prospective designs and direct biomarkers of platelet activation and inflammation.

Some limitations should be noted. First, the retrospective design limits causal inference and increases the possibility of residual confounding. Second, the sample size was modest and the follow-up duration was short. Third, MPV may be affected by pre-analytical and laboratory-related factors. Finally, the study was conducted at a single center, which may limit generalizability.

Despite these limitations, the study has strengths. It included a concurrent untreated control group, evaluated within-person changes, compared change scores between groups, and performed adjusted regression analyses to address baseline differences and potential confounding. The findings should be considered hypothesis-generating and may support larger prospective studies evaluating whether tirzepatide influences platelet indices and inflammatory pathways beyond weight reduction.

Conclusion

In patients with obesity, two months of tirzepatide therapy was associated with significant reductions in BMI and MPV compared with untreated controls. The association between tirzepatide treatment and MPV reduction persisted after adjustment for baseline BMI, baseline MPV, age, and sex. However, because MPV is a surrogate marker and no direct inflammatory or platelet-function biomarkers were assessed, these findings should be interpreted as preliminary and hypothesis-generating. Larger prospective studies with longer follow-up and comprehensive biomarker assessment are warranted [5, 11–14, 16].

Abbreviations

BMI

Body mass index

CI

Confidence interval

CRP

C-reactive protein

fL

Femtoliter

GIP

Glucose-dependent insulinotropic polypeptide

GLP-1

Glucagon-like peptide-1

IL-6

Interleukin-6

MPV

Mean platelet volume

SPSS

Statistical Package for the Social Sciences

WHO

World Health Organization

Author contributions

FD designed the study, collected and analyzed the data, interpreted the results, and drafted the manuscript. OVO contributed to study design, data interpretation, and critical revision of the manuscript. NG supervised the study, contributed to interpretation of the findings, and critically revised the manuscript. All authors read and approved the final manuscript.

Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Data availability

The datasets analyzed during the current study are available from the corresponding author on reasonable request, subject to institutional and ethical restrictions.

Declarations

Ethics approval and consent to participate

The study was approved by Firat University Ethic Committee (approval date: 22.01.2026; approval number: 43742). The requirement for informed consent was waived because of the retrospective design.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.