Efficacy and safety benefits of HR17031, a fixed‐ratio combination of INS068 and noiiglutide, versus its components alone in Chinese patients with type 2 diabetes uncontrolled on oral antidiabetic drug(s): A phase 2, multicentre, open‐label, randomised, parallel three‐arm, treat‐to‐target trial

Abstract Aims To assess the efficacy and safety of HR17031, a fixed‐ratio combination of basal insulin analogue (INS068) and GLP‐1 receptor agonist (noiiglutide), versus its components alone in patients with type 2 diabetes uncontrolled on metformin with or without a second oral antidiabetic drug. Materials and Methods This phase 2 multicentre trial randomised 455 patients with type 2 diabetes (HbA1c 7.5%–11.0% [58.0–97.0 mmol/mol]; previous metformin ± another oral antidiabetic drug) 2:2:1 to HR17031 ( n = 183), INS068 ( n = 182) or noiiglutide ( n = 90). The primary endpoint was HbA1c change from baseline to week 26. Results HR17031 achieved a greater reduction in HbA1c than INS068 and noiiglutide (−2.4% [−26 mmol/mol] vs. −1.5% [−16 mmol/mol] and −1.7% [−19 mmol/mol]), indicating superiority for HR17031 over both INS068 and noiiglutide (least‐squares mean difference = −0.9% [−10 mmol/mol] and −0.7% [−7 mmol/mol], respectively; both p < 0.0001). More patients reached HbA1c target <7.0% (53 mmol/mol) and ≤6.5% (48 mmol/mol) with HR17031 (<7.0%, 81.4%; ≤6.5%, 74.3%) than INS068 (47.8%; 26.4%) and noiiglutide (55.6%; 41.1%). HR17031 resulted in no weight gain in contrast to INS068 (−0.1 vs. 2.0 kg; p < 0.0001). Incidence of level 2/3 hypoglycaemia was similar with HR17031 (5.5%) and INS068 (4.4%), and lower with noiiglutide (1.1%). HR17031 demonstrated fewer instances of nausea (7.2%), diarrhoea (7.2%), and vomiting (2.8%) than noiiglutide (15.6%, 21.1%, and 20.0%). Conclusions HR17031 is effective and well‐tolerated in patients with type 2 diabetes uncontrolled on metformin with or without a second oral antidiabetic drug.