The GLP-1 receptor agonist exenatide may be a better alternative to insulin for the management of cystic fibrosis-related diabetes (CFRD), a pilot study carried out by respiratory physicians and endocrinologists in South Australia suggests.
In a study involving six young people with CF, pancreatic exocrine insufficiency and impaired glucose tolerance (IGT), they found that a subcutaneous injection of exenatide (2.5mg) prevented the postprandial hyperglycaemic response.
Exenatide appeared to exert its effect on postprandial hyperglycaemia by slowing gastric emptying time, according to Dr Myfanwy Geyer and colleagues at the Women’s and Children’s Hospital and the University of Adelaide.
When they assessed the impact of exenatide compared to placebo in a crossover study of two doses, the postprandial AUC240 for blood glucose was reduced from 1814 to 1431 mmol/L and the peak glucose level was reduced from 9.53 to 7.65 mmol/L.
Insulin, C-peptide, and incretin concentrations were significantly reduced after exenatide compared to placebo, whereas glucagon levels did not differ.
Gastric emptying was markedly slower after exenatide compared to placebo according to measures of 10% gastric emptying (139 vs 55 minutes).
Writing in Diabetes Obesity and Metabolism, the researchers – including respiratory physicians Dr Andrew Tai and Dr James Martin – said CF-related diabetes was the most common co-morbidity of CF, affecting up to 30% of patients, and treatment could improve pulmonary function and BMI.
“However, the only current treatment available for CFRD is insulin, which carries a risk of hypoglycaemia and can be a significant burden given the need for frequent injections and blood glucose monitoring.”
If the efficacy of exenatide is confirmed in further longer-term studies in larger numbers of patients with CFRD it could offer a less burdensome approach than insulin, they said.
The researchers acknowledged that other GLP-1 agonists and DPP-4 inhibitors had advantages in terms of dosing methods and schedules, but they were less suitable than exenatide for managing postprandial hyperglycaemia because they had lesser effects of gastric emptying.
However, exenatide’s potential for weight loss would have to be anticipated with careful selection of patients with CF, who were “classically lean or underweight,” they added.