994-P: Effects of Dulaglutide and Trelagliptin on ß-Cell Function after One Year in Patients with Type 2 Diabetes: DUET-Beta Extension Study

Abstract

Studies on glucagon-like peptide 1 receptor agonists (GLP-1-RA) and dipeptidyl peptidase-4 inhibitors (DPP-4-I) have suggested positive effects on beta-cells. However, direct comparison between weekly GLP-1-RA: dulaglutide (Dula) and weekly DPP-4-I: trelagliptin (Trela) effects on beta-cell function is not known. Thus, we compared the effects of Dula and Trela on beta-cell function in patients with type 2 diabetes (T2D) in an open-label, parallel-group, randomized controlled 24-week trial, with an additional 28 weeks of extension follow-up. Beta-cell function and insulin resistance were assessed by HOMA2-%β and HOMA2-IR, respectively. Body composition was also assessed by the bioelectrical impedance method. Fifty metformin ± basal insulin-treated patients with type 2 diabetes (T2D) were randomized to Dula 0.75 mg/week or Trela 100 mg/week. Forty-eight patients entered the 28-weeks extension study and continued their allocated therapy. Forty-six completed (Dula: n = 23, Trela: n = 23) the 52-week exposure and were included in the analysis. HOMA2-%β was higher in the Dula group than in the Trela group throughout the 52 weeks (24 weeks: Dula: +50.6 ± 9.9% vs. Trela: +7.5 ± 9.5%, p = 0.003; 52 weeks: Dula: +54.5 ± 8.7% vs. Trela: +3.0 ± 8.7%, p <0.001). HOMA2-IR was not significantly different between both groups (24 weeks: Dula: -0.29 ± 0.50 vs. Trela: -0.19 ± 0.50, p = 0.88; 52 weeks: Dula: +0.79 ± 0.52 vs. Trela: +0.45 ± 0.52, p = 0.64). At 52 weeks, HbA1c had a larger decrease with the Dula group (Dula: -0.52 ± 0.11%, Trela: -0.13 ± 0.12%, p = 0.02). Body fat mass was reduced more in the Dula group than the Trela group (52 weeks: Dula: -1.5 ± 0.3 kg vs. Trela: +0.4 ± 0.3 kg, p <0.001). However, Dula patients did not have a reduction in skeletal muscle mass (52 weeks: 0.0 ± 0.3 kg, p = 0.94). In conclusion, Dula increased HOMA2-%β level more than Trela over the 52 weeks, without a significant change in HOMA2-IR level. Dula reduced body fat mass without skeletal muscle mass loss. Disclosure Y. Kondo: None. S. Satoh: None. Y. Terauchi: Advisory Panel; Self; AstraZeneca, Daiichi Sankyo Company, Limited, Eli Lilly and Company, Merck Sharp & Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Novo Nordisk A/S, Sanofi. Research Support; Self; Daiichi Sankyo Company, Limited, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novartis Pharmaceuticals Corporation, Novo Nordisk A/S, Ono Pharmaceutical Co., Ltd., Sanofi, Shionogi & Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd. Speaker's Bureau; Self; Astellas Pharma Inc., AstraZeneca, Bayer Yakuhin, Ltd., Daiichi Sankyo Company, Limited, Eli Lilly and Company, Merck Sharp & Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Novartis Pharmaceuticals Corporation, Novo Nordisk A/S, Ono Pharmaceutical Co., Ltd., Sanofi, Sanwa Kagaku Kenkyusho, Shionogi & Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd.