Safety and efficacy of IDegLira titrated once weekly versus twice weekly in patients with type 2 diabetes uncontrolled on oral antidiabetic drugs: DUAL VI randomized clinical trial

Aims To compare the safety and efficacy of a simpler titration algorithm for insulin degludec/liraglutide (IDegLira) with that used in previous DUAL trials in insulin-naive patients with type 2 diabetes. Research design and methods This 32-week, open-label, non-inferiority trial randomized adults with type 2 diabetes uncontrolled on metformin ± pioglitazone to receive IDegLira, titrated either once weekly, based on the mean of 2 pre-breakfast plasma glucose (PG) readings (n = 210), or twice weekly, based on the mean of 3 pre-breakfast PG readings (n = 210). Results Mean HbA1c decreased from 8.2% (65 mmol/mol) to 6.1% (43 mmol/mol) with once-weekly titration and from 8.1% (65 mmol/mol) to 6.0% (42 mmol/mol) with twice-weekly titration; non-inferiority was confirmed (estimated treatment difference: 0.12% [−0.04; 0.28]95% CI , 1.30 mmol/mol [−0.41; 3.01]95% CI ). Approximately 90% of patients achieved HbA1c < 7% in each arm. Mean fasting PG was similar after 32 weeks. Weight change was −1.0 kg vs −2.0 kg for once-weekly vs twice-weekly titration. Rates of severe or blood glucose-confirmed symptomatic hypoglycaemia were low in both arms: 0.16 events/patient-year of exposure (PYE) for once-weekly, 0.76 events/PYE for twice-weekly titration. Mean IDegLira dose at 32 weeks was 41 dose steps (41 U IDeg/1.48 mg Lira) for both arms. Overall adverse event rates were 207.8 and 241.3 events/100 PYE with once-weekly and twice-weekly titration, respectively. Conclusion A pragmatic titration algorithm with once-weekly adjustments based on 2 PG readings resulted in a safety and glycaemic efficacy profile similar to that with twice-weekly adjustments based on 3 preceding PG values in insulin-naive patients.