THU279 Long duration Of CFTR Modulators Consistently Improve Glucose Metabolism Parameters In Patients With Cystic Fibrosis

Disclosure: A. Cohen: None. A. Mass: None. D. Zangen: None. M. Cohen-Cymberknoh: None. Background: Impaired glycemic control and consequently Cystic fibrosis Related Diabetes (CFRD) due to gradual pancreatic β-cell dysfunction is a common complication (upto 50% in adults) in patients with cystic fibrosis (CF.) The novel use of CFTR modulators (CFTRm), improve pulmonary function and reduce disease exacerbations. Data regarding the long-term effect of CFTRm on glycemic control is limited. In this observational-retrospective study, we evaluate the effect of CFTRm on the classical pathophysiological deterioration in glucose tolerance in patients with CF. Methods and Results: 15 patients with CF (ages 13-37) treated with CFTRm were followed by routine Oral Glucose Tolerance Test (OGTT). OGTT Results of Pre and 3-81 months (mean 28) post initiation of CFTRm therapy were compared and also classified to 4 classic categories: normal glucose tolerance (NGT), indeterminate (INDET), impaired glucose tolerance (IGT) and diabetes (CFRD). The end point of OGTT at 120 minutes significantly improved post CFTRm therapy being 159.7 (80-419.4) compared to 130.4 (54-286) pre-CFTRm (p = 0.047). Regarding the categories sub-classification of patients: Two patients with CFRD improved after CFTRm therapy to NGT or INDET. 2 with INDET pre-therapy improved to NGT post therapy.Of 3 patients with IGT, 2 improved to NGT or INDET and 1 worsened to CFRD. Out of the 6 patients who had NGT pre CFTRm therapy, 4 remained NGT, one worsened to INDET, and one became CFRD. Conclusions: This is the first and largest study so far demonstrating consistent significant improvement in glycemic control in CFRD after CFTRm treatment of at least 3 months duration. Treatment seems to delay and possibly reverse the deterioration in glycemic control that is typical to the natural history of patients with cystic fibrosis. Larger studies are indicated but awareness to the current findings may prevent hypoglycemic events while staying on a fixed insulin dose while on CFTRm therapy. Presentation: Thursday, June 15, 2023