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Context: Colonic polyps occur in 30-40% of acromegalic patients, increasing the risk of colon carcinoma. Although debated, there is emerging evidence that metformin may play a protective role in diabetic and non-diabetic patients with colonic polyps and its use in chemoprevention is currently explored., Objective: Evaluate the prevalence of colonic polyps in acromegalic patients treated or not with metformin and explore its possible protective role., Design: Exploratory cross-sectional study in two tertiary Italian referral centres., Met: hods: Out of 153 acromegalic patients, we selected 58 patients (36-82 years; f: 33) who had at least one colonoscopy performed within the first 2 years of diagnosis. Presence of colonic polyps/cancer and related risk factors, current metformin and acetylsalicylic acid intake, disease duration, therapies for acromegaly, hormonal and metabolic parameters were assessed., Results: An overall prevalence of 36% polyps was found. Based on the presence of polyps, we identified two groups, comparable for age, BMI, disease duration, glucose, insulin, HOMA-IR, HbA1c, GH and IGF-I levels. Of the patients with polyps (including three adenocarcinomas) only 24% were treated with metformin vs 57% of patients without polyps. Multivariate analysis confirmed a significant negative association between colonic polyps and metformin intake (OR: 0.22, 95% CI: 0.06-0.77, P = 0.01), whereas no significant association was found between polyps and age (P = 0.10), overweight/obesity (P = 0.54), smoking (P = 0.15), acetylsalicylic acid intake (P = 0.99), disease duration (P = 0.96), somatostatin analogues treatment (P = 0.70)., Conclusions: These findings, though deriving from an exploratory study, could suggest a protective role of metformin on the development of colonic polyps in acromegaly, and need to be confirmed in an extended study population.