Introduction and Objective: Preserving β-cell function may delay or prevent progression to CF-related diabetes, a major comorbidity in people with PI-CF. This study aimed to evaluate whether weekly GLP-1 agonist therapy improves β- and α-cell function and post-prandial glucose tolerance in people with PI-CF and AGT. Methods: In this randomized, open-label, cross-over study, participants received dulaglutide 0.75 mg weekly for 6 doses, with a matched 6-week observation period. Mixed-meal tolerance tests (MMTT) were performed at each period start and end. Non-parametric methods estimated between-condition differences in change in biomarkers of islet function (C-peptide, glucagon, glucose) as assessed by area under the curve (AUC) at 30 and 180 min.Results: To date, 11 participants with PI-CF and AGT (mean±SE age 26.9 ± 2.2 y, BMI 27.3 ± 1.8 kg/m2, HbA1c 5.7 ± 0.1%) have completed the study. Early-phase C-peptide (incremental AUC at 30 min) in the dulaglutide period was lower when compared to observation (p<0.05), but when adjusted for glucose showed an increase (iAUCC-pep/iAUCglc ratio, Δ 0.25 ng-min/mg %, p<0.01). Total glucagon AUC at 180 min was lower in the dulaglutide period (16.4% decrease vs 1.8% increase, p<0.05). Glucose at 30 and 180 min trended lower in the dulaglutide period (-4202.3 mg-min/dL, p=0.06). A weak trend for weight reduction during treatment vs observation periods was observed (−1.88 kg ± 0.89 vs −0.14 kg ± 0.55, p=0.18). Some subjects reported worsening acid reflux (n=3) and constipation (n=4) in the dulaglutide period. Conclusion: GLP-1 agonist therapy in patients with PI-CF and AGT appears to enhance early-phase β-cell insulin secretion and suppress α-cell glucagon secretion. These effects may contribute to an improvement in post-prandial glucose tolerance. Patients with PI-CF should be cautioned regarding acid reflux and constipation when considering GLP-1 agonist therapy.
S. Reddy: None. R.R. Bhatia: None. A. Peleckis: None. P. Alvarado: None. R. Walega: None. D. Stefanovski: None. R.J. Gallop: None. D. Hadjiliadis: None. A. Flatt: Employee; Vertex Pharmaceuticals Incorporated. R.C. Rubenstein: None. C.L. Chan: None. A. Kelly: None. M.R. Rickels: Consultant; Vertex Pharmaceuticals Incorporated, Sernova, Corp. Research Support; Dompé, Tandem Diabetes Care, Inc. Consultant; Novo Nordisk.
National Institutes of Health (R01 DK97830, UL1 TR001878, and P30 DK019525)
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