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

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.

Keywords

• beta‐cell regeneration
• dipeptidyl‐peptidase IV inhibitor
• exercise
• glucagon‐like peptide‐1
• interleukin 6
• type 1 diabetes mellitus