Nikolaos Angelopoulos¹ , Ioannis Androulakis¹, Andreas Rizoulis¹, Anastasios Boniakos¹, Evangelos Fousteris²,
Voula Mentzelopoulou¹, Valentina Petkova¹, Rodis Paparodis¹, Dimitra Zianni¹, Dimos Florakis³, Areti Korakovouni¹, Zadalla Mouslech⁴,
Sarantis Livadas¹ and Ploutarchos Tzoulis⁵

© The Author(s), under exclusive licence to Springer Nature Limited 2025

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.

International Journal of Obesity; https://doi.org/10.1038/s41366-025-01986-0