Exercise and the dipeptidyl-peptidase IV inhibitor sitagliptin do not improve beta-cell function and glucose homeostasis in long-lasting type 1 diabetes-A randomised open-label study.

ABSTRACT

BACKGROUND: Increasing evidence points to beta-cell regeneration in individuals with type 1 diabetes mellitus (type 1 DM) at all stages of the disease. Exercise and glucagon-like peptide-1 (GLP-1) independently improve beta-cell function and glucose homeostasis in animal studies and in clinical trials in individuals with type 2 diabetes mellitus (type 2 DM). Whether a combination of both, exercise and GLP-1, induces a similar effect in individuals with long-lasting type 1 DM remains to be investigated. METHODS: In an open-label study, participants with long-standing type 1 DM were randomly assigned to oral sitagliptin 100 mg daily for 12 weeks in combination with or without an exercise intervention. The primary end-point was change in the area under the concentration-time curve of C-peptide during a mixed meal tolerance test before and after 12 weeks of intervention. RESULTS: A total of 24 participants were included in the study and treated with sitagliptin, 12 participants were allocated to a 12-week exercise intervention. After 12 weeks, there was no difference in the change of AUC C-peptide between groups (exercise 0 [-1424 to 1870], no exercise 2091 [283-17 434]; P = 0.09). HDL improved in the exercise intervention group compared to the group with sitagliptin only (exercise 0.11 [-0.09 to 0.27]; no exercise -0.18 [-0.24 to 0.01]; P = 0.04). AUC glucose was numerically slightly lower in the exercise intervention group but this did not translate into changes in HbA1c. CONCLUSION: The combination of exercise and sitagliptin had no effect on beta-cell function in individuals with long-lasting type 1 DM.