Insulin and Oral Agents for Managing Cystic Fibrosis-Related Diabetes

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Background: The Cystic Fibrosis Foundation recommends both short-term and long-acting insulin therapy when cystic fibrosis-related diabetes has been diagnosed. Diagnosis is based on: an elevated fasting blood glucose level greater than 6.94 mmol/liter (125 mg/deciliter); or symptomatic diabetes for random glucose levels greater than 11.11 mmol/liter (200 mg/deciliter); or glycated hemoglobin levels of at least 6.5%. Objectives: To establish the effectiveness of agents for managing diabetes in people with cystic fibrosis in relation to blood sugar levels, lung function and weight management. Search methods: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. We also handsearched abstracts from pulmonary symposia and the North American Cystic Fibrosis Conferences. Date of the most recent search of the Group's Cystic Fibrosis Trials Register: 22 July 2013. Selection criteria: Randomized controlled trials comparing all methods of diabetes therapy in people with diagnosed cystic fibrosis-related diabetes. Data collection and analysis: Two authors independently extracted data and assessed the risk of bias in the included studies. Main results: The searches identified 19 studies (28 references). Three studies (107 participants) are included: one comparing insulin with oral repaglinide and no medication (short-term single-center study of seven patients with cystic fibrosis-related diabetes and normal fasting glucose); one comparing insulin with oral repaglinide and placebo (long-term multi-center study with 81 patients, 61 of whom had cystic fibrosis-related diabetes); and one 12-week single-center study comparing the long-acting insulin, glargine to short-term neutral protamine Hagedorn insulin. The long-term trial of insulin and repaglinide demonstrated no significant difference between treatments. In the smaller study comparing insulin and oral repaglinide, there were two incidents of significant hypoglycemia in the insulin group compared to one in the repaglinide group; in the larger study there were five incidents of significant hypoglycemia in the insulin group and six in the repaglinide group. The study comparing glargine to neutral protamine Hagedorn insulin demonstrated a statistically non-significant weight increase in with longer-acting insulin given at bedtime and reported a mean of six hypoglycemia events in the glargine group compared to five events in the neutral protamine Hagedorn insulin group. None of the three included studies were powered to show a significant improvement in lung function. Authors' conclusions: This review has not found any significant conclusive evidence that long-acting insulins, short-acting insulins or oral hypoglycemic agents have a distinct advantage over one another in controlling hyperglycemia or clinical outcomes associated with cystic fibrosis-related diabetes. While some cystic fibrosis centers use oral medications to help control diabetes, the Cystic Fibrosis Foundation (USA) clinical practice guidelines support the use of insulin therapy and this remains the most widely-used treatment method. Randomized controlled trials specifically related to controlling diabetes with this impact on the course of pulmonary disease process in cystic fibrosis continue to be a high priority. There is no demonstrated advantage yet established for using oral hypoglycemic agents over insulin, and further studies need to be evaluated to establish whether there is clear benefit for using hypoglycemic agents. Agents that potentiate insulin action, especially agents with additional anti-inflammatory potential should be further investigated to see if there may be a clinical advantage to adding these medications to insulin as adjuvant therapy.



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