Effect of Lumacaftor/Ivacaftor on glucose metabolism and insulin secretion in Phe508del homozygous cystic fibrosis patients

Abstract
Objective: To examine the effects of Lumacaftor/Ivacaftor on glucose metabolism and insulin secretion in patients with cystic fibrosis (CF) who are homozygous for the Phe508del mutation.

Methods: A standard oral glucose tolerance test (OGTT) and an intravenous glucose tolerance test (IVGTT) were conducted to assess glucose metabolism and insulin secretion before and after 6-8 weeks of Lumacaftor/Ivacaftor treatment in five Phe508del-homozygous CF patients. The area under the curve (AUC) for glucose and insulin levels was calculated using the trapezoidal method.

Results: Five participants were studied. Following treatment with Lumacaftor/Ivacaftor, three patients showed improvement in 2-hour glucose levels, while two experienced a decline. Analysis of the blood glucose levels during the OGTT indicated an increase in AUC for three of the five patients. In the IVGTT, acute insulin secretion improved in two patients but worsened in three.

Conclusion: This study did not find a consistent effect of Lumacaftor/Ivacaftor on glucose tolerance or insulin secretion. Further adequately powered studies are necessary to comprehensively evaluate the drug’s impact on glucose metabolism and to determine if it can help prevent cystic fibrosis-related diabetes VX-809 (CFRD).