Improvements in Glucose Regulation in Children and Young People with Cystic Fibrosis-Related Diabetes following Initiation of Elexacaftor/Tezacaftor/Ivacaftor

Abstract

Introduction: Cystic fibrosis transmembrane receptor (CFTR) modulators are increasingly used in children and young people with Cystic Fibrosis (CF). Data in adults show there may be an impact on glycaemic control in those with CF related diabetes (CFRD). Paediatric data are rare. Case series/presentation: Children aged > 12 years with CFRD, who were eligible for Elexacaftor/Tezacaftor/Ivacaftor (ELX/TEZ/IVA) were commenced on treatment. Glucose monitoring via the Libre freestyle system was commenced prior to, immediately after and several months after commencing ELX/TEZ/IVA. Glycaemic control, shown by time in range (3 – 10 mmol/L), percentage of time spent hypoglycaemic (<3mmol/L) and percentage of time spent hyperglycaemic (>10mmol/L) on Insulin doses were recorded. Following ELX/TEZ/IVA, four of seven children stopped insulin, two required substantially reduced doses of insulin, one showed no response. Glycaemic control remained similar on lower doses or no insulin. Hypoglycaemia was detected in those not requiring insulin. Discussion/Conclusion: ELX/TEZ/IVA has a positive impact on glycaemic control and insulin requirements in children with CFRD. Close monitoring is required when commencing treatment. Children with CFRD need counselling regarding possible reductions in insulin requirement and re-education regarding symptoms, signs and management of hypoglycaemia.

The Effects of Elexacaftor, Tezacaftor, and Ivacaftor (ETI) on Blood Glucose in Patients With Cystic Fibrosis: A Systematic Review

“…While a substantial number of patients transitioned to a category indicating improved glucose tolerance (e.g., a transition from CFRD to impaired glucose tolerance or from impaired to normal glucose tolerance), a few patients exhibited changes in the other direction toward less effective glycemic control (Figure 2). Similarly, Park et al [32] noted that six of the seven patients they studied were able to decrease or entirely eliminate the use of insulin following initiation of ETI, but one patient with an extremely high HbA1c at baseline saw her HbA1c value increase dramatically after beginning ETI therapy and slightly increased her insulin dosage. It is not clear whether the effects of ETI may differ between patients based on prior CFRD diagnosis.…”

“…Eight out of the 11 studies with a patient sample size greater than one reported a statistically significant improvement in at least one blood glucose measure (Table 2). The studies that did not find any statistically significant improvements [24,31,32] were all ones with small sample sizes, ranging from 4 to 11 patients for each measure. Across all studies, four of six (67%) comparisons with a patient sample >20 showed a statistically significant improvement in blood glucose measures pre-and post-ETI, compared to only six of 28 (21%) comparisons with a sample size ≤ 20, suggesting that small sample sizes may have been limiting the power of studies to detect the effects of ETI (Table 2).…”

“…In addition, in many of the studies, some patients were insulin users. The authors of several of the studies mentioned that some of their subjects either decreased their dosages or stopped using insulin completely after initiating ETI therapy [21,24,28,32,33]. The reported mean (or median) effects of ETI on blood glucose in these studies may therefore underestimate the effects that would be seen absent from these changes in insulin use.…”

“…FIGURE 2: Patient transitions in glycemic status on OGTTs before and after initiating ETI therapy ETI: Elexacaftor, tezacaftor, and ivacaftor; NGT: Normal glucose tolerance; INDET: Indeterminate glucose tolerance; IGT: Impaired glucose tolerance; AGT: Abnormal glucose tolerance; CFRD: Cystic fibrosis-related diabetes; OGTT: Oral glucose tolerance test Data for this figure created by the authors have been combined from[24,27,32,34]. The terms and categorizations are those of the authors of each paper.…”

Evolving nutritional needs, obesity, and overweight status in cystic fibrosis

“…Screening oral glucose tolerance tests are a component of routine CF care to detect CFRD as early as possible. Multiple studies have identified significant positive impact on glycemic control and insulin requirements after initiation of HEMT [30 ▪ ,31]. Close glucose monitoring following initiation of HEMT is warranted to avoid potential hypoglycemia or excess insulin use.…”