Effects of elexacaftor / tezacaftor / ivacaftor triple combination therapy on glycaemic control and body composition in patients with cystic fibrosis-related diabetes

Cystic fibrosis transmembrane conductance regulator (CFTR) modulators are a group of new drugs for the treatment of cystic fibrosis (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 are limited to small studies with conflicting results. We conducted a prospective observational study on 24 CF patients with CF-related diabetes requiring insulin therapy, with the aim to evaluate the effectiveness of ETI on glucose metabolism, glucose variability and body composition. After six months of treatment, HbA1c and coefficient of variation, measured through continuous glucose monitoring, significantly decreased (median changes: -0.5, P = 0.029 and -6.3, P = 0.008, respectively), despite unchanged insulin requirements. Over the treatment period, percent of fat mass increased by a median value of 3% (p= 0.029).