AIM: Two treatment strategies were compared in patients with type 2 diabetes (T2DM) on basal insulin requiring intensification: addition of once-daily (OD) liraglutide (Lira) or OD insulin aspart (IAsp) with largest meal. METHODS: Subjects completing 104 weeks (52-week main trial BEGIN ONCE-LONG + 52-week extension) on insulin degludec (IDeg) OD + metformin with HbA1c ≥ 7.0% (≥53 mmol/mol) were randomized to IDeg+Lira [n = 88, mean HbA1c: 7.7% (61 mmol/mol)] or IDeg+IAsp (n = 89, mean HbA1c: 7.7%) for 26 weeks, continuing metformin. Subjects completing 104 weeks with HbA1c <7.0% continued IDeg + metformin in a third, non-randomized arm (n = 236). RESULTS:IDeg+Lira reduced HbA1c (-0.74%-points) significantly more than IDeg+IAsp (-0.39%-points); estimated treatment difference (ETD) (IDeg+Lira-IDeg+IAsp) -0.32%-points (95% CI -0.53; -0.12); p = 0.0024. More IDeg+Lira (49.4%) than IDeg+IAsp (7.2%) subjects achieved HbA1c <7.0% without confirmed hypoglycaemia [plasma glucose <3.1 mmol/l (<56 mg/dl) or severe hypoglycaemia) and without weight gain; estimated odds ratio (IDeg+Lira/IDeg+IAsp) 13.79 (95% CI 5.24; 36.28); p < 0.0001. IDeg+Lira subjects had significantly less confirmed and nocturnal confirmed hypoglycaemia, and significantly greater weight loss (-2.8 kg) versus IDeg+IAsp (+0.9 kg); ETD (IDeg+Lira-IDeg+IAsp) -3.75 kg (95% CI -4.70; -2.79); p < 0.0001. Other than more gastrointestinal side effects with IDeg+Lira, no safety differences occurred. Durability of IDeg was established in the non-randomized arm, as mean HbA1c remained <7.0% [mean 6.5% (48 mmol/mol) at end-of-trial]. CONCLUSIONS:IDeg+Lira improved long-term glycaemic control, with weight loss and less hypoglycaemia versus adding a single daily dose of IAsp in patients with T2DM inadequately controlled with IDeg + metformin.
RCT Entities:
AIM: Two treatment strategies were compared in patients with type 2 diabetes (T2DM) on basal insulin requiring intensification: addition of once-daily (OD) liraglutide (Lira) or OD insulin aspart (IAsp) with largest meal. METHODS: Subjects completing 104 weeks (52-week main trial BEGIN ONCE-LONG + 52-week extension) on insulin degludec (IDeg) OD + metformin with HbA1c ≥ 7.0% (≥53 mmol/mol) were randomized to IDeg+Lira [n = 88, mean HbA1c: 7.7% (61 mmol/mol)] or IDeg+IAsp (n = 89, mean HbA1c: 7.7%) for 26 weeks, continuing metformin. Subjects completing 104 weeks with HbA1c <7.0% continued IDeg + metformin in a third, non-randomized arm (n = 236). RESULTS:IDeg+Lira reduced HbA1c (-0.74%-points) significantly more than IDeg+IAsp (-0.39%-points); estimated treatment difference (ETD) (IDeg+Lira-IDeg+IAsp) -0.32%-points (95% CI -0.53; -0.12); p = 0.0024. More IDeg+Lira (49.4%) than IDeg+IAsp (7.2%) subjects achieved HbA1c <7.0% without confirmed hypoglycaemia [plasma glucose <3.1 mmol/l (<56 mg/dl) or severe hypoglycaemia) and without weight gain; estimated odds ratio (IDeg+Lira/IDeg+IAsp) 13.79 (95% CI 5.24; 36.28); p < 0.0001. IDeg+Lira subjects had significantly less confirmed and nocturnal confirmed hypoglycaemia, and significantly greater weight loss (-2.8 kg) versus IDeg+IAsp (+0.9 kg); ETD (IDeg+Lira-IDeg+IAsp) -3.75 kg (95% CI -4.70; -2.79); p < 0.0001. Other than more gastrointestinal side effects with IDeg+Lira, no safety differences occurred. Durability of IDeg was established in the non-randomized arm, as mean HbA1c remained <7.0% [mean 6.5% (48 mmol/mol) at end-of-trial]. CONCLUSIONS:IDeg+Lira improved long-term glycaemic control, with weight loss and less hypoglycaemia versus adding a single daily dose of IAsp in patients with T2DM inadequately controlled with IDeg + metformin.