12-month weight-loss trajectories and predictors of response to tirzepatide under individualized dosing: A multicenter real-world study

Background and aims: Real-world evidence on 12-month treatment effectiveness and persistence with tirzepatide remains limited, particularly under individualized dosing and self-funded treatment conditions. We evaluated 12-month tirzepatide outcomes in routine clinical practice. Methods: This was a multicenter, retrospective, observational real-world study including 249 adults with overweight or obesity treated with tirzepatide across 13 obesity practices in Greece. Treatment was entirely self-funded, and dose escalation was individualized rather than protocol driven. Treatment persistence, reasons for discontinuation, weight loss, dose trajectories, metabolic outcomes, and predictors of 12-month response were evaluated. Results: At 12 months, 170/249 patients (68.3%) remained on treatment, 64 (25.7%) had confirmed discontinuation, and 15 (6.0%) were lost to follow-up. Among patients with available weight measurements, mean weight loss was 19.9 ± 8.6% at 12 months, with 88.9%, 50.0%, and 27.2% achieving ≥10%, ≥20%, and ≥25% weight loss, respectively. Mean tirzepatide dose at 12 months was 9.71 mg. Among 179 patients assessed at both 6 and 12 months, 70.4% experienced >2% additional weight loss during the second 6 months, whereas 10.1% experienced >2% weight regain. Six-month percentage weight loss was not significantly associated with additional weight loss between months 6 and 12 after multivariable adjustment (β = −0.110, P = 0.135). Among 139 participants who had not achieved ≥20% weight loss at month 6, early response demonstrated moderate discrimination for achieving this cumulative threshold at month 12 (AUC 0.760, 95% bootstrap CI 0.675–0.837), with an adjusted OR of 1.34 per additional percentage point of 6-month weight loss (P