Introduction: Cystic fibrosis related diabetes (CFRD) is the most common extra pulmonary complication of cystic fibrosis (CF). Cystic fibrosis transmembrane conductance regulator (CFTR) modulators are a group of new drugs for the treatment of CF and elexacaftor+tezacaftor+ivacaftor (ETI) triple combination therapy has been approved as first choice therapy in the treatment of patients with at least 1 copy of F508del mutation. Data on the effects of CFTR modulators on glucose metabolism in patients with or without CFRD are limited to small studies with conflicting results. Aim of the study: to evaluate the effectiveness of ETI on glucose metabolism, glucose variability and body composition in patients with CFRD. Methods: We conducted a prospective observational study on 24 CF patients with CFRD requiring insulin therapy. We performed an evaluation of glycometabolic control, glucose variability (assessed with 14 days-flash glucose monitoring) and body composition (with bio-impedance analysis) before and six months after the beginning of ETI. Data are expressed as median and interquartile ranges. Results: We demonstrated an improvement in both HbA1c [from 7.0% (6.5, 7.4) to 6.6 (6.0, 7.1), p<0,05] and coefficient of variation [CV - from 35.0 (29.0, 44.5) to 28.2 (25.2, 33.1), p< 0.01], despite unchanged insulin requirements. Over the treatment period, percent of fat mass (FM) significantly increased [from 12.1% (7.2, 16.2) to 15.4% (11.8, 18.6), p<0.05]. Conclusions: ETI improves glycometabolic regulation in patients with CFRD on insulin therapy. A longer follow-up is needed to better characterize the body composition changes induced by ETI and their metabolic consequences. Disclosure V.Grancini: None. A.Gramegna: None. L.Zazzeron: None. G.Alicandro: None. L.L.Porcaro: None. F.V.Piedepalumbo: None. C.Lanfranchi: None. V.Daccò: None. E.Orsi: None.