Effects of Dulaglutide and Trelagliptin on Beta-Cell Function in Patients with Type 2 Diabetes—The DUET-Beta Study

Abstract

Some studies of glucagon-like peptide 1 receptor agonists (GLP-1-RA) and dipeptidyl peptidase-4 inhibitors (DPP-4-I) have shown positive effects on beta-cells. A direct comparison between weekly GLP-1-RA: dulaglutide (Dula) and weekly DPP-4-I: trelagliptin (Trela) effects on beta-cell function has not yet been performed. We compared the effects of Dula and Trela on beta-cell function in type 2 diabetes (T2D) patients in an open-label, parallel-group, randomized controlled trial. Patients received Dula 0.75 mg/week or Trela 100 mg/week for 24 weeks. Beta-cell function was assessed using a glucagon stimulation test (GST)-based disposition index (DI = area under the curve of C-peptide during 6 min GST ÷ HOMA2-IR). The primary endpoint was the difference between the two groups in the change in DI over the 24-week treatment period. Body composition was assessed using the bioelectrical impedance method. Fifty metformin ± basal insulin-treated patients with T2D were randomized to Dula or Trela. Forty-eight patients completed 24 weeks of weekly administration of Dula (n = 23) or Trela (n = 25). The change in DI during 24 weeks was not different between the groups (Dula: +0.34 ± 0.49, Trela: +0.57 ± 0.47, p = 0.74). However, the change in HOMA2-%β was higher in the Dula group than in the Trela group (Dula: +50.6 ± 9.9% vs. Trela: +7.5 ± 9.5%, p = 0.003). HbA1c decreased to a greater extent in the Dula group (Dula: -0.77 ± 0.07%, Trela: -0.57 ± 0.07%, p = 0.04). Body weight reduced more in the Dula group than the Trela group (Dula: -1.4 ± 0.3 kg vs. Trela: -0.3 ± 0.3 kg, p = 0.02). Body fat mass reduced more in the Dula group than the Trela group (Dula: -1.2 ± 0.3 kg vs. Trela: -0.3 ± 0.2 kg, p = 0.02). Dula did not reduce skeletal muscle mass (-0.2 ± 0.1 kg, p = 0.31). In conclusion, the effects of Dula and Trela on beta-cell function were not different in GST-based DI. However, Dula increased the HOMA2-%β level more than Trela. Dula reduced body fat mass without causing skeletal muscle mass loss. Disclosure Y. Kondo: None. S. Satoh: None. Y. Terauchi: Research Support; Self; MSD K.K.. Speaker's Bureau; Self; MSD K.K.. Advisory Panel; Self; MSD K.K.. Research Support; Self; Ono Pharmaceutical Co., Ltd.. Speaker's Bureau; Self; Ono Pharmaceutical Co., Ltd.. Research Support; Self; Novartis Pharma K.K., Boehringer Ingelheim GmbH. Speaker's Bureau; Self; Boehringer Ingelheim GmbH. Advisory Panel; Self; Boehringer Ingelheim GmbH. Research Support; Self; Mitsubishi Tanabe Pharma Corporation. Speaker's Bureau; Self; Mitsubishi Tanabe Pharma Corporation. Advisory Panel; Self; Mitsubishi Tanabe Pharma Corporation. Research Support; Self; Daiichi Sankyo Company, Limited. Speaker's Bureau; Self; Daiichi Sankyo Company, Limited. Advisory Panel; Self; Daiichi Sankyo Company, Limited. Research Support; Self; Sanwa Kagaku Kenkyusho Co., Ltd.. Speaker's Bureau; Self; Sanwa Kagaku Kenkyusho Co., Ltd.. Research Support; Self; Novo Nordisk Inc.. Speaker's Bureau; Self; Novo Nordisk Inc.. Advisory Panel; Self; Novo Nordisk Inc.. Research Support; Self; Eli Lilly and Company. Speaker's Bureau; Self; Eli Lilly and Company. Advisory Panel; Self; Eli Lilly and Company. Research Support; Self; Sanofi. Speaker's Bureau; Self; Sanofi. Advisory Panel; Self; Sanofi. Research Support; Self; Sumitomo Dainippon Pharma Co., Ltd.. Speaker's Bureau; Self; Sumitomo Dainippon Pharma Co., Ltd.. Research Support; Self; Shionogi & Co., Ltd.. Speaker's Bureau; Self; Shionogi & Co., Ltd., Bayer Yakuhin, Ltd., Astellas Pharma US, Inc., AstraZeneca. Advisory Panel; Self; AstraZeneca, Teijin Pharma Limited.