Summary: This post hoc analysis of the ADJUNCT ONE and ADJUNCT TWO randomised trials asked who discontinues adjunctive liraglutide in type 1 diabetes because of adverse events. Non-completers had longer disease duration (25.8 vs 21.0 years, p<0.0001 in ADJUNCT ONE), more often undetectable C-peptide (91.5% vs 81.3%), and lower baseline BMI (27.8 vs 29.8 kg/m², p<0.0001). It describes determinants of discontinuation, not treatment efficacy.
PICO Summary
| Element | Detail |
|---|---|
| Population | Adults with type 1 diabetes pooled from two phase 3 placebo-controlled trials, ADJUNCT ONE (NCT01836523) and ADJUNCT TWO (NCT02098395); post hoc comparison of completers versus participants who discontinued because of adverse events or lack of tolerance. |
| Intervention | Adjunctive liraglutide (1.8, 1.2, or 0.6 mg daily) added to insulin therapy. |
| Comparison | Placebo added to insulin therapy; the discontinuation analysis pooled both arms and also stratified completers versus non-completers within each treatment group. |
| Outcome | Across both arms, non-completers had longer T1D duration (ADJUNCT ONE 25.8 vs 21.0 years, p<0.0001; ADJUNCT TWO 24.1 vs 21.0 years, p=0.04), lower baseline BMI (27.8 vs 29.8 kg/m², p<0.0001; 26.3 vs 29.2 kg/m², p<0.0001), lower daily insulin doses, and more often undetectable C-peptide (91.5% vs 81.3%; 87.0% vs 84.9%). When stratified by treatment, only T1D duration and C-peptide distinguished completers from non-completers among liraglutide-treated participants, not placebo. Adverse event rates were higher in non-completers. No effect estimates with 95% CI, ARR, or NNT were reported for this descriptive analysis. |
Expert Commentary
This is a descriptive, hypothesis-generating post hoc analysis, and it should be read as such. It does not test whether liraglutide works in type 1 diabetes; the parent ADJUNCT trials already showed only modest, weight-favourable glycaemic effects offset by hyperglycaemia and ketosis signals, and adjunctive GLP-1 use in type 1 diabetes remains off-label. What this paper adds is a profile of who walks away. The signal is internally consistent: people with longer-standing disease, little or no residual beta-cell function, and lower BMI were more likely to stop because of adverse events or poor tolerance, and within the liraglutide arm specifically, disease duration and undetectable C-peptide were the distinguishing features. The central limitation is the design itself. Comparisons are unadjusted, with no multivariable modelling, no correction for multiple testing, and a pooled-arm primary analysis that blurs whether the pattern is drug-specific or simply marks a frailer phenotype. The work was conducted and partly authored by the manufacturer, which warrants the usual caution. Can I use this with my patients? Not as an efficacy argument, but it is a reasonable counselling cue: a long-duration, lean, C-peptide-negative patient considering off-label liraglutide should be warned tolerance may be poor. I would welcome a prospective, adjusted analysis before these characteristics drive selection.
References
Shah VN, Agesen RM, Bardtrum L, Christiansen E, Snaith J, Greenfield JR. Determinants of liraglutide treatment discontinuation in type 1 diabetes: a post hoc analysis of ADJUNCT ONE and ADJUNCT TWO randomized placebo-controlled clinical studies. J Diabetes Sci Technol. 2024;19(2):321-331. doi:10.1177/19322968241305647