Benefits of insulin degludec/liraglutide are maintained even in patients discontinuing sulphonylureas or dipeptidyl peptidase‐4 inhibitors upon initiation of degludec/liraglutide therapy: A post hoc analysis of the DUAL II and DUAL IX trials

Abstract

Aim To investigate the efficacy and safety of initiating insulin degludec/liraglutide (IDegLira) in patients with type 2 diabetes (T2D) who had discontinued pretrial sulphonylureas (SUs) or dipeptidyl peptidase‐4 inhibitors (DPP4is) versus patients not previously treated with these regimens. Materials and Methods In DUAL II, patients with T2D uncontrolled on basal insulin and metformin ± SU/glinides were randomized to insulin degludec or IDegLira (both capped at 50 U). In DUAL IX, patients were randomized to insulin glargine U100 (no maximum dose) or IDegLira, as add‐on to sodium‐glucose co‐transporter‐2 inhibitors ± oral antidiabetic drugs. In this post hoc analysis, patients were grouped according to pretrial use of SU (DUAL II) or DPP4i (DUAL IX). Results Regardless of pretrial SU/DPP4i use, IDegLira was favourable versus insulin comparators with respect to change in HbA1c and body weight. Lower hypoglycaemia rates and comparable end‐of‐trial daily insulin dose were achieved with IDegLira, regardless of pretrial regimen. There was no clinically relevant increase in mean self‐measured blood glucose in the early weeks after IDegLira initiation. There was no statistically significant interaction between the randomized treatments and previous SU/DPP4i use. Conclusions IDegLira was more favourable compared with degludec or glargine U100 in terms of change in HbA1c and body weight, regardless of antecedent treatment. Clinicians should be aware of a potential transient rise in self‐measured blood glucose when transitioning therapy in patients. This shows that SUs/DPP4is can be safely discontinued, without deterioration in glycaemic control when initiating IDegLira, allowing a simplified treatment regimen.

Efficacy of iGlarLixi in adults with type 2 diabetes inadequately controlled (glycated haemoglobin ≥8%, ≥64 mmol/mol) on two oral antidiabetes drugs: Post hoc analysis of the LixiLan‐O randomized trial

“…A recent post hoc analysis compared the FRC of insulin degludec and liraglutide (IDegLira) with basal insulin in participants from the DUAL II and DUAL IX trials, including those whose T2D was inadequately controlled with multiple OADs. 16 Individuals who had been taking a sulphonylurea discontinued it while continuing metfor- This research is limited by its post hoc nature; the study was not designed or powered to test for differences among treatment arms within the subgroup of participants with HbA1c ≥8% (≥64 mmol/mol) who were taking two OADs at baseline. These findings must therefore be considered exploratory.…”

“…Other recent research has evaluated treatment with an FRC among those who might be candidates for intensification of previous therapy. A recent post hoc analysis compared the FRC of insulin degludec and liraglutide (IDegLira) with basal insulin in participants from the DUAL II and DUAL IX trials, including those whose T2D was inadequately controlled with multiple OADs 16 . Individuals who had been taking a sulphonylurea discontinued it while continuing metformin and beginning randomized treatment with IDegLira or insulin degludec; those who had been taking a dipeptidyl peptidase‐4 (DPP‐4) inhibitor discontinued it while continuing to take a sodium‐glucose cotransporter protein‐2 inhibitor (with or without other OADs) and beginning IDegLira or insulin glargine.…”

“…A recent post hoc analysis compared the FRC of insulin degludec and liraglutide (IDegLira) with basal insulin in participants from the DUAL II and DUAL IX trials, including those whose T2D was inadequately controlled with multiple OADs. 16 Individuals who had been taking a sulphonylurea discontinued it while continuing metformin and beginning randomized treatment with IDegLira or insulin degludec; those who had been taking a dipeptidyl peptidase‐4 (DPP‐4) inhibitor discontinued it while continuing to take a sodium‐glucose cotransporter protein‐2 inhibitor (with or without other OADs) and beginning IDegLira or insulin glargine. Those with prior sulphonylurea use had a mean baseline HbA1c of 8.75%‐8.85% (72 to 73 mmol/mol), and those with prior DPP‐4 inhibitor use had a mean baseline HbA1c of 8.18%‐8.20% (66 mmol/mol).…”