Six‐Month Real‐World Effectiveness, Persistence and Safety of Low‐to‐Moderate Dose Tirzepatide in Adults With Obesity: A Multicentre Observational Study

AIMS: To evaluate 6-month weight-loss outcomes, treatment persistence, and safety of low- to moderate-dose tirzepatide in a real-world clinical setting. METHODS: This multicentre retrospective observational study evaluated adults with obesity who initiated tirzepatide in routine clinical practice across 15 endocrinology clinics in Greece between December 2024 and May 2025. Patients with available baseline and 6-month follow-up (±2 weeks) data were included. Changes in body weight and body mass index (BMI) were assessed, while treatment persistence, reasons for discontinuation, and adverse events were recorded. Continuous variables were analysed using paired parametric or non-parametric tests as appropriate. RESULTS: A total of 260 patients initiated tirzepatide, of whom 208 (80%) completed 6 months of therapy. Median percentage weight loss was substantial, with 94.2% achieving ≥ 5% weight loss, 77.9% ≥ 10%, 47.1% ≥ 15% and approximately 20% ≥ 20%. Body weight and BMI decreased significantly from baseline (p < 0.001), with a large effect size. Weight-loss magnitude was independent of baseline BMI and obesity class, while women achieved a greater percentage weight loss than men (p = 0.042). Treatment discontinuation occurred in 20% of patients, most commonly during the titration phase, primarily due to goal achievement, cost, non-response or adverse events. Gastrointestinal adverse events were the most frequently reported but rarely led to treatment discontinuation. CONCLUSIONS: In routine clinical practice, low-to-moderate dose tirzepatide was associated with clinically meaningful weight loss at 6 months, high treatment persistence, and acceptable tolerability. These findings provide real-world evidence supporting the medium-term effectiveness of tirzepatide across obesity severity in everyday endocrinology practice. TRIAL REGISTRATION: ACTRN12625000071426.