Determinants of Liraglutide Treatment Discontinuation in Type 1 Diabetes: A Post Hoc Analysis of ADJUNCT ONE and ADJUNCT TWO Randomized Placebo-Controlled Clinical Studies.

INTRODUCTION

Two phase 3 randomized controlled studies (ADJUNCT ONE (Clinicaltrials.gov: NCT01836523), ADJUNCT TWO (Clinicaltrials.gov: NCT02098395)) evaluated liraglutide (1.8, 1.2 or 0.6 mg) vs placebo in participants with type 1 diabetes (T1D) as an adjunct to insulin therapy. This paper aims to improve our understanding of the potential mechanisms leading to premature discontinuation of this treatment regimen.

METHODS

Post hoc comparisons were conducted on baseline characteristics and adverse event (AE) rates of participants completing and not completing the ADJUNCT studies due to AEs/lack of tolerance using summary tables and variance analysis.

RESULTS

Non-completers (liraglutide and placebo combined) had lower baseline body mass index (BMI) (ADJUNCT ONE: 27.8 kg/m vs 29.8 kg/m, < .0001; ADJUNCT TWO: 26.3 kg/m vs 29.2 kg/m, < .0001), longer duration of T1D (25.8 years vs 21.0 years, < .0001; 24.1 years vs 21.0 years, = .04), lower daily insulin doses by continuous infusion (46.4 U vs 57.3 U, = .01; 40.9 U vs 57.4 U, = .12) or multiple injections (58.4 U vs 68.5 U, = .006; 56.0 U vs 65.8 U, =.03) and a higher proportion of participants with undetectable C-peptide (91.5% vs 81.3%; 87.0% vs 84.9%) compared to completers. When analyzed by treatment group, only duration of T1D and C-peptide differed between completers and non-completers among liraglutide (and not placebo) participants. The AE rates were higher for non-completers.

CONCLUSION

Individuals with longer-standing T1D and low levels of C-peptide at baseline were more likely to discontinue adjunctive liraglutide treatment due to AEs/lack of tolerance than individuals with residual insulin production. Lower BMI predicted a greater likelihood of non-completion for the included participants, regardless of treatment. These new findings may be relevant for clinical practice.