Orkambi Not Seen to Significantly Improve Blood Glucose Levels in CF Patients in Small Study

Analysis of blood glucose levels in cystic fibrosis (CF) patients being treated with Orkambi (ivacaftor/lumacaftor) shows that the therapy has minimal impact on glycemic control, a small study reports.

Up to 50 percent of adults with cystic fibrosis develop diabetes, making so-called CF-related diabetes (CFRD) the most common comorbidity, or coexisting condition, in these patients.

The molecular mechanism behind CFRD development is still under investigation, but it is believed to be linked to the cystic fibrosis transmembrane conductance regulator protein (CFTR), the protein that is altered in CF and that is present in pancreatic cells that normally produce insulin.

Therefore, treatments that target CFTR, such as Vertex Pharmaceuticals‘ Orkambi, may also help with tackling diabetes in CF patients. There have been some studies in this regard; however, the results have not been conclusive. Some believe this is due to the method used in assessing blood glucose levels.

In the study, “Continuous glucose monitoring in youth with cystic fibrosis treated with lumacaftor-ivacaftor,” published in the Journal of Cystic Fibrosis, researchers assessed the effect of Orkambi on blood glucose levels in CF patients using a variety of techniques.

The study involved nine young CF patients, six of whom were male, at a median age of 12.7 years, who had the F508del mutation in the CFTR gene — the cause of their CF.

Blood glucose levels were measured using a technique known as continuous glucose monitoring (CGM), which is one of the most sensitive methods for detecting blood glucose abnormalities. CGM measures were performed twice, once before (median of 26 weeks) and once after (median of 29 weeks) starting treatment with Orkambi. The minimum treatment time was three months.

Other methods were also used to assess blood glucose, namely measurement of HbA1c levels, which is a measure of the average blood glucose over a period of time, and oral glucose tolerance tests (OGTT), which assess how well the body handles sugar (glucose) from food.

Results showed that although there was an increase in blood glucose levels measured by HbA1c and OGTT after Orkambi treatment, these levels were still within the normal range. Blood glucose measurements using the more sensitive CGM method did not show any difference in blood glucose levels before and after treatment.

When looking at the results more closely, males in the group showed some improvement in blood glucose control compared with females, but the study group was quite small and included only three female patients.

Overall, the team concluded that the “findings do not support significant improvements in glycemic outcomes in CF youth with early glucose abnormalities after the start of lumacaftor-ivacaftor [Orkambi],” and suggest that the therapy only has a “minimal impact.”

The researchers emphasize, however, that “future studies in young children on CFTR modulators are required to determine whether intervention at an earlier age, or more highly effective combination CFTR modulator, may have greater impacts on β-cell function [cells that store and release insulin] and glucose metabolism.”