Metabolic dysfunction contributes to lower urinary tract symptoms (LUTS) through mechanisms involving impaired bladder contractility, autonomic dysregulation, and increased pelvic pressure. Prospective real-world data integrating symptom, functional, and metabolic outcomes remain limited. This study evaluated the longitudinal impact of tirzepatide on LUTS severity, urinary flow, and glycaemic control.

We conducted a prospective observational study of 67 men with moderate-to-severe LUTS (IPSS ≥8) initiating tirzepatide in routine clinical practice. Patients were followed over 24 weeks. Primary outcomes were change in IPSS and maximum urinary flow rate (Qmax). Secondary outcomes included quality of life (QoL), prostate-specific antigen (PSA), and glycated haemoglobin (HbA1c). Analyses included paired comparisons and trajectory assessment.

IPSS improved from 19.4 ± 4.3 to 12.4 ± 3.9 (Δ −7.0; p < 0.001). Qmax increased modestly from 9.7 ± 2.4 to 11.8 ± 2.9 mL/s (Δ +2.1 mL/s; p = 0.01). QoL improved from 4.4 ± 0.9 to 2.8 ± 0.8 (p < 0.001). HbA1c decreased from 90 to 58 mmol/mol (p < 0.001), while PSA remained stable (2.1 vs 2.0 ng/mL; p = 0.48). Symptom improvement occurred early, whereas Qmax showed gradual modest gains.

The present findings demonstrate that treatment with tirzepatide is associated with clinically meaningful improvement in LUTS severity, alongside significant metabolic optimisation. The magnitude of IPSS reduction observed in this cohort suggests a substantial symptomatic benefit that is comparable to, or exceeds, improvements reported with conventional medical therapies in selected populations.

In contrast, the improvement in Qmax was modest, indicating that the observed urinary benefit is unlikely to be driven by structural changes in bladder outlet obstruction. This interpretation is further supported by the stability of PSA levels, suggesting no significant effect on prostate volume. Instead, the pattern of early symptom improvement followed by gradual and limited changes in flow rate supports a predominantly functional mechanism.

The moderate correlation between HbA1c reduction and both IPSS and Qmax improvements reinforces the hypothesis that metabolic control plays a contributory role in LUTS pathophysiology. Improved glycaemic status may enhance detrusor function, reduce autonomic dysfunction, and alleviate systemic inflammation, collectively contributing to improved urinary dynamics.

These findings align with emerging evidence linking metabolic syndrome to LUTS, and suggest that systemic metabolic optimisation may represent an adjunctive therapeutic pathway in selected patients. However, given the observational design and absence of a control group, causality cannot be established, and the results should be considered hypothesis-generating.

Tirzepatide is associated with clinically meaningful improvement in LUTS and glycaemic control, with modest improvement in Qmax. Findings suggest a metabolic-functional mechanism rather than structural prostate change and warrant further controlled studies.