Effects of dulaglutide and trelagliptin on beta-cell function in patients with type 2 diabetes: a randomized controlled study: DUET-beta study.

Aims: This randomized, open-label, parallel-group, controlled trial compared the effects of dulaglutide and trelagliptin on beta-cell function in patients with type 2 diabetes.

Materials And Methods: For 24 weeks, participants received dulaglutide (0.75 mg/week) or trelagliptin (100 mg/week), after which beta-cell function was evaluated using a glucagon stimulation test-based disposition index. The primary endpoint was the change in disposition index over the 24-week treatment period.

Results: Fifty patients with type 2 diabetes who received metformin with or without basal insulin were randomized to receive dulaglutide or trelagliptin. Forty-eight patients completed the 24-week dulaglutide ( = 23) or trelagliptin ( = 25) treatment. The dulaglutide group reduced HbA1c levels more than the trelagliptin group (dulaglutide: - 0.77% ± 0.07% vs. trelagliptin: - 0.57% ± 0.07%;  = 0.04). Change in disposition index during the 24 weeks did not differ between the groups (dulaglutide: - 0.07 ± 1.08 vs. trelagliptin: + 0.59 ± 1.04;  = 0.66), but the dulaglutide group increased HOMA2-%β levels more than the trelagliptin group (dulaglutide: + 26.2 ± 4.3% vs. trelagliptin: + 5.4 ± 4.1%;  = 0.001). The dulaglutide group showed greater body fat mass reduction than the trelagliptin group (dulaglutide: - 1.2 ± 0.3 kg vs. trelagliptin: - 0.3 ± 0.2 kg;  = 0.02) without skeletal muscle mass loss.

Conclusion: Dulaglutide and trelagliptin had similar effects on beta-cell function according to the glucagon stimulation test-based disposition index. However, dulaglutide promoted improved HOMA2-%β levels compared to trelagliptin and body fat mass was reduced without loss of skeletal muscle mass (UMIN-CTR 000024164).

Supplementary Information: The online version contains supplementary material available at 10.1007/s13340-024-00717-6.