THU294 Glucagon Like Peptide-1 Analogue Therapy In Obese Patients With Cystic Fibrosis Related Diabetes

Abstract Disclosure: A.R. Ankireddypalli: None. A. Moheet: None. Introduction: Cystic fibrosis (CF) has classically been associated with malnutrition and being underweight. Intense emphasis on nutritional augmentation and advancement in medical therapies including recent introduction of CFTR modulators have significantly reduced the prevalence of malnutrition in CF. However, this success has been accompanied by a significant rise in overweight/obesity in CF. Recent studies have reported that one-third of all adult CF patients are overweight or obese. Glucagon like peptide receptor-1 agonists (GLP-1RA) therapy is an effective treatment for type 2 diabetes mellitus (T2DM) and obesity. Current guidelines for CF related diabetes (CFRD), recommend insulin as the mainstay of treatment. However, with increase in prevalence of obesity, there is increased interest in examining the role of incretin-based therapies in CFRD. Gastrointestinal (GI) symptoms like abdominal pain, steatorrhea, gastroparesis are common in CF. Concerns about the potential GI side effects had previously dampened the enthusiasm for these drugs in CF.The objective of this case series is to demonstrate impact on glycemic control and weight, and tolerability of GLP1-RA treatment in obese patients with CFRD and pancreatic insufficiency (PI) after 1 year of therapy. Case 1: A 21-year-old female with CF (delta F508 homozygote) and PI, was diagnosed with CRFD at 15 years. She was initially on lantus 14 units daily with HbA1c of 6.7%. She was started on CFTR modulator therapy and with increase in BMI from 37 to 45 in 1 year with HbA1c of 8.9%. She was started on semaglutide and tolerated the medication well with no GI side effects. 1 year later her BMI reduced to 42 and HbA1c was 8.2%. Case 2: A 62-year-old male with CF (delta F508 heterozygote) and PI, diagnosed with CFRD at age 44 years. He was on lantus 66 units and aspart 1 unit per 5 grams carbohydrate coverage. He was started on CFTR modulator and in 1 year BMI increased from 53 to 57. He was started on semalglutide, which he tolerated well with no GI symptoms. 1 year later his Hba1c improved to 7% with a BMI of 54. Discussion: In this era of CFTR modulator therapy, CF patients are faced with changing metabolic parameters, including weight gain and developing T2DM phenotype with insulin resistance. There is one previous case report of short duration of GLP-1RA use in CFRD. We report > 1 year of clinical experience of GLP-1RA use in 2 patients. GLP-1RA was well tolerated in these patients with improvement in glycemic control and weight loss. GLP-1 RA should be considered in obese, PI patients with CFRD as an add-on therapy to insulin. However, larger studies with long-term follow up are required to study the full impact of GLP-1RA to establish it as a treatment option in CFRD. Presentation: Thursday, June 15, 2023