CFDB - Cystic Fibrosis DataBase

primary studies published RCT

Lumacaftor/Ivacaftor Treatment of Patients with Cystic Fibrosis Heterozygous for F508del-CFTR.

Study design (if review, criteria of inclusion for studies)

Randomized double-blind trial

Participants

Twenty-six adults from Children's Hospital of Philadelphia and University of Pennsylvania CF Center with PI-CF and AGT (defined by oral glucose tolerance test glucose [mg/dL]: early glucose intolerance [1-hour ≥155 & 2-hour <140], impaired glucose tolerance [2-hour ≥140 and <200 mg/dl], or diabetes [2-hour ≥200]). 24 completed the trial (n=12 sitagliptin; n=12 placebo).

Interventions

Patients were randomized to a 6-month double-blind trial of DPP-4 inhibitor sitagliptin 100 mg daily or matched-placebo

Outcome measures

Main outcome measures were mixed-meal tolerance test (MMTT) responses for intact GLP-1 and GIP, insulin secretory rates (ISR), glucagon suppression, and glycemia and glucose-potentiated arginine (GPA) test-derived measures of β- and α-cell function.

Main results

Following 6-months of sitagliptin vs. placebo, MMTT intact GLP-1 and GIP responses increased (P <0.001), ISR dynamics improved (P <0.05), and glucagon suppression was modestly enhanced (P <0.05) while GPA test responses for glucagon were lower. No improvements in glucose tolerance or β-cell sensitivity to glucose, including for second-phase insulin response were found.

Authors' conclusions

In glucose intolerant PI-CF, sitagliptin intervention augmented meal-related incretin responses with improved early insulin secretion and glucagon suppression without affecting post-prandial glycemia.

Keywords: Sitagliptin; Hypoglycemic Agents; pharmacological_intervention; Diabetes Mellitus; Pancreatic Diseases; Gastrointestinal Diseases;