Effect of adding insulin degludec to treatment in patients with type 2 diabetes inadequately controlled with metformin and liraglutide: a double-blind randomized controlled trial (BEGIN: ADD TO GLP-1 Study)

Aim: To evaluate the efficacy and safety of adding insulin degludec (IDeg) to treatment in patients with type 2 diabetes receiving liraglutide and metformin and qualifying for treatment intensification because of inadequate glycaemic control. Methods: In this 26-week, double-blind trial, patients who still had inadequate glycaemic control after a 15-week run-in period with initiation and dose escalation of liraglutide to 1.8mg in combination with metformin (>= 1500 mg) were randomized to addition of once-daily IDeg ('IDeg add-on to liraglutide' arm; n= 174) or placebo ('placebo add-on to liraglutide' arm; n= 172), with dosing of both IDeg and placebo based on titration guidelines. Results: At 26 weeks, the mean change in glycated haemoglobin level was greater in the IDeg add-on to liraglutide arm (-1.04%) than in the placebo add-on to liraglutide arm (-0.16%; p< 0.0001). Similarly, the mean fasting plasma glucose reduction was greater, and self-measured plasma glucose values were lower at all eight time points, with IDeg add-on versus placebo add-on (both p< 0.0001). At 26 weeks, the IDeg dose was 51 U (0.54 U/kg). During the run-in period with liraglutide, body weight decreased by similar to 3 kg in both groups. After 26 weeks, the mean change was + 2.0 kg (IDeg add-on to liraglutide) and -1.3 kg (placebo add-on to liraglutide). Confirmed hypoglycaemia rates were low in both groups, although higher with IDeg than with placebo (0.57 vs. 0.12 episodes/patient-years of exposure; p= 0.0002). Nocturnal confirmed hypoglycaemia was infrequent in both groups, with no episodes of severe hypoglycaemia, and no marked differences in adverse events with either treatment approach. Conclusion: The addition of liraglutide and IDeg to patients sub-optimally treated with metformin and liraglutide and requiring treatment intensification was found to be effective and well-tolerated.