Comparison of clinical efficacy and safety of weekly glucagon‐like peptide‐1 receptor agonists dulaglutide and semaglutide in Japanese patients with type 2 diabetes: Randomized, parallel‐group, multicentre, open‐label trial (COMING study)

Abstract Aim To compare the clinical usefulness of once‐weekly glucagon‐like peptide‐1 receptor agonists dulaglutide and semaglutide at the doses approved for use in Japanese patients with type 2 diabetes. Methods In total, 120 patients with glycated haemoglobin (HbA1c) ≥7% were randomly assigned to dulaglutide (n = 59) or semaglutide group (n = 61), and 107 participants (dulaglutide/semaglutide = 53/54) completed the 24‐week trial. The primary endpoint was the difference of HbA1c level between the two groups at 24 weeks. Results HbA1c level at 24 weeks was significantly lower in the semaglutide group (7.9 ± 0.5%‐6.7 ± 0.5%) compared with the dulaglutide group (8.1 ± 0.6%‐7.4 ± 0.8%) ( p < .0001). Reduction in body mass index and visceral fat area were also more significant in the semaglutide group ( p < .05, respectively). The achievement rate of HbA1c <7% was higher in the semaglutide group ( p < .0001). The parameters such as low‐density lipoprotein cholesterol, alanine aminotransferase and γ‐glutamyl transpeptidase were decreased in the semaglutide group. Surprisingly, only semaglutide group significantly improved the apolipoprotein B/A1 ratio, which is considered a useful myocardial infarction risk index. Using computed tomography, the liver to spleen ratio was significantly elevated only in the semaglutide group. In contrast, gastrointestinal symptoms were observed in 13.2% of dulaglutide and 46.3% of semaglutide group ( p < .01). The Diabetes Treatment‐Related Quality of Life scores related to pain and gastrointestinal symptoms were also superior in the dulaglutide group. Conclusions This prospective trial showed that semaglutide has more pronounced glucose‐ and body mass index‐lowering effects and reduces liver fat percentage and visceral fat area and that dulaglutide has less gastrointestinal symptoms and superior Diabetes Treatment‐Related Quality of Life scores related to pain and gastrointestinal symptoms.