Risk-stratified pharmacologic strategies for secondary prevention after acute diverticulitis: an exploratory narrative review and research framework

Background Recurrent acute diverticulitis (RAD) affects up to one-third of patients after the first episode and is associated with impaired quality of life and increased healthcare burden. Although interest in pharmacological prophylaxis is increasing, adequately powered randomized trials have not shown consistent benefits for any agent. Aims Synthesize current evidence on pharmacological strategies for secondary prevention of diverticulitis, evaluate the potential of risk stratification and propose an exploratory framework to inform future studies. Methods We conducted a structured narrative review in accordance with the SANRA criteria, including randomized controlled trials, observational studies, systematic reviews and international guidelines published between 1995 and 2026. Studies on primary prevention or symptomatic uncomplicated diverticular disease (SUDD) were assessed separately as indirect evidence. Results Although subgroup analyses have suggested possible benefits in selected high-risk populations, large randomized trials have not demonstrated a reduction in recurrence with mesalazine or rifaximin. Evidence regarding probiotics remains inconclusive and is largely limited to SUDD. Currently, the major international guidelines do not recommend the use of pharmacological agents for routine secondary prevention. Emerging data indicate that radiologic features, endoscopic severity (DICA score), and biomarker findings, may help identify patients at increased risk of recurrence. Conclusions Currently, no pharmacological therapy is available for the universal secondary prevention of diverticulitis. We propose a hypothesis-generating, risk-stratified framework that integrates clinical, endoscopic and radiological markers to support individualized trial design and patient selection. This approach may help guide future randomized studies and refine the preventive strategies.