Abstract
Tirzepatide, a dual GIP/GLP-1 receptor agonist, has shown substantial weight-loss efficacy in clinical trials, though typically at higher doses and longer treatment durations. Evidence on the short-term real-world effectiveness of low-dose tirzepatide in adults with obesity without diabetes is limited. In this prospective multicentre observational study, 115 adults with obesity but without diabetes were treated with tirzepatide 2.5 mg weekly for 4 weeks, titrated to 5 mg for a total of 12 weeks. Anthropometric and biochemical parameters were assessed at baseline and week 12. Mean body weight decreased by 8.2 ± 4.9 kg (−7.3% ±4.4%), with a BMI reduction of 2.8 ± 1.7 kg/m²; 46.1% achieved ≥5% weight loss. HbA1c decreased from 5.6 ± 0.4% to 5.4 ± 0.3%, LDL cholesterol from 113 ± 30.4 to 106 ± 28 mg/dL, and triglycerides from 123.6 ± 56.1 to 119.2 ± 44.5 mg/dL, while HDL cholesterol and eGFR remained unchanged. Nausea was the most common adverse event (7.8%), and treatment discontinuation occurred in 10.4%, mainly among individuals previously treated with GLP-1 receptor agonists. Low-dose tirzepatide resulted in clinically meaningful short-term weight loss and favorable metabolic effects, supporting its effectiveness and tolerability in real-world practice.
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Data availability
The datasets generated and/or analyzed during the current study are not publicly available due to patient privacy and ethical restrictions but are available from the corresponding author upon reasonable request. All requests will be reviewed by the Hellenic Endocrine Network Ethics Committee to ensure compliance with institutional and national regulations on data sharing.
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NA, SL and RP conceived and designed the study. AR, IA, VM, EF, AB, VP, DZ, DF, AK and ZM contributed to patient recruitment and data collection. NA performed the statistical analyses. NA and PT drafted the initial version of the manuscript. All authors contributed to data interpretation, critically revised the manuscript for important intellectual content, approved the final version for submission, and agree to be accountable for the accuracy and integrity of the work. NA and DZ are the guarantors of this work and take full responsibility for the integrity of the data and the accuracy of the analyses.
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Angelopoulos, N., Androulakis, I., Rizoulis, A. et al. A real-world study of tirzepatide for weight loss in adults without diabetes mellitus. Int J Obes 50, 684–688 (2026). https://doi.org/10.1038/s41366-025-01986-0
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DOI: https://doi.org/10.1038/s41366-025-01986-0


