Aims
Evaluate 26 weeks’ liraglutide treatment in type 1 diabetes (T1D) by subgroups in the ADJUNCT ONE and TWO trials.
Materials and Methods
ADJUNCT ONE and TWO were randomized controlled phase 3 trials in 1,398 and 835 participants with T1D treated with liraglutide (1.8, 1.2 or 0.6 mg) or placebo (adjuncts to insulin). This post hoc analysis evaluated treatment effects by subgroups: HbA1c (textless or ≥ 8.5; body mass index (BMI) (textless or ≥ 27 kg/m2) and insulin regimen (basal bolus or continuous subcutaneous insulin infusion).
Results
In both trials at week 26, reductions in HbA1c, body weight and daily insulin dose did not differ significantly (ptextgreater0.05) by baseline HbA1c or BMI. Risk of clinically significant hypoglycemia or hyperglycemia with ketosis did not differ significantly (ptextgreater0.05) by baseline HbA1c, BMI or insulin regimen. At week 26 in ADJUNCT ONE, these risks did not differ (ptextgreater0.05) between treatment groups. Placebo-adjusted reductions in HbA1c, body weight and insulin dose (-0.30 points, -5.0 kg, and -12 respectively, with liraglutide 1.8 mg) were significant (ptextless0.05), greater than at week 52 and similar to those in ADJUNCT TWO (-0.35 -4.8 kg and -10 respectively, with liraglutide 1.8 mg).
Conclusions
In ADJUNCT ONE and TWO, the efficacy and glycemic safety of liraglutide did not depend on subgroups, leaving residual beta-cell function the only identified parameter impacting the effect of glucagon-like peptide-1 receptor agonists (GLP-1 RA) in T1D. These findings support a role for GLP-1 RAs as adjuncts to insulin in T1D, warranting further study.