ESPE Yearbook of Paediatric Endocrinology

To read the full abstract: Lancet Diabetes and Endocrinology 2018; 6: 114–121

Cystic fibrosis (CF)-related diabetes (CFRD) impacts significantly on mortality and quality of life. Impaired glucose metabolism and CFRD are associated with poor weight and height gain and impaired lung function in children and adolescents (1). In that study, height and weight were lower in CF patients with diabetes than those without, not only at diagnosis of CFRD, but also years before that. After CFRD diagnosis, height and weight declined even further in CFRD patients. In contrast, no reduction of BMI was observed. All analyzed lung function parameters showed a marked decline in CFRD patients starting 1 year prior to CFRD diagnosis (1).

Hence, life expectancy of patients with cystic fibrosis largely depends upon complications and comorbidities and importantly upon the treatment of accompanying conditions such as CFRD. Currently, the recommended treatment for CFRD is insulin, but some patients receive oral antidiabetic drugs to ease the treatment burden. Clinical trials to assess the efficacy and safety of oral antidiabetic drugs in patients with CFRD are needed.

This multicentre, open-label, industry-sponsored randomised controlled trial in 49 centres in Austria, France, Germany, and Italy included patients with CF aged 10+ years with newly diagnosed CFRD. Patients were randomised to receive either insulin injections or oral repaglinide. The primary outcome was mean change in HbA1c from baseline to 24 months of treatment. Instead of intention-to-treat analyses, patients who stopped treatment early because of lack of efficacy were excluded. Out of 34 patients in the repaglinide group and 41 in the insulin group, 30 and 37, respectively, were included in the analyses.

At 24 months, HbA1c was no different between groups (mean change from baseline 0.2% [S.D. 0.7%], 1.7 mmol/mol [8.1] with repaglinide vs −0.2% [1.3%], −2.7 mmol/mol, [14.5] with insulin; mean difference −0.4%, (95% CI −1.1 to 0.2 [−4.4 mmol/mol, −11.5 to 2.7], P=0.15). As expected for patients with CF, the most frequent adverse events were pulmonary events (43/107 [40%] with repaglinide and 60/133 [45%] with insulin), and the most frequent serious adverse events were pulmonary events leading to hospital admission (5/10 [50%] and 7/13 [54%], respectively).

In summary, oral repaglinide was as efficacious and safe as insulin in patients with CFRD. Whether repaglinide is equally effective in increasing BMI and life expectancy in such patients will need further study. Since patients with CF have to adhere to multiple treatments, avoiding the need for injections seems worthwhile.

Reference: 1. Terliesner N, Vogel M, Steighardt A, Gausche R, Henn C, Hentschel J, Kapellen T, Klamt S, Gebhardt J, Kiess W, Prenzel F. Cystic-fibrosis related-diabetes is preceded by and associated with growth failure and deteriorating lung function. J Pediatr Endocrinol Metab. 2017 Aug 28;30(8):815–821.