Randomized 52-week phase 2 trial of albiglutide versus placebo in adult patients with newly diagnosed type 1 diabetes

Context: GLP-1 receptor agonists are an established therapy in patients with type 2 diabetes;however, their role in type 1 diabetes remains to be determined.Objective: Determine efficacy and safety of once-weekly albiglutide 30 mg (up-titration to50 mg at week 6) versus placebo together with insulin in patients with new-onset type 1diabetes and residual insulin production.Design: 52-week, randomized, phase 2 study (NCT02284009).Methods: A prespecified Bayesian approach, incorporating placebo data from a prior study,allowed for 3:1 (albiglutide:placebo) randomization. The primary endpoint was 52-week changefrom baseline in mixed meal tolerance test (MMTT) stimulated 2-h plasma C-peptide area underthe curve (AUC). Secondary endpoints included metabolic measures and pharmacokinetics ofalbiglutide.Results: 12/17 (70.6%, placebo) and 40/50 (80.0%, albiglutide) patients completed thestudy. Within our study, mean (standard deviation) change from baseline to week 52 inMMTT-stimulated 2-h plasma C-peptide AUC was-0.16 nmol/L (0.366) with placebo and-0.13 nmol/L (0.244) with albiglutide. For the primary Bayesian analysis (including prior studydata) the posterior treatment difference (95% credible interval) was estimated at 0.12 nmol/L(0-0.24); the probability of a difference =0.2 nmol/L between treatments was low (0.097).A transient significant difference in maximum C-peptide was seen at week 28. Otherwise,no significant secondary endpoint differences were noted. On-therapy adverse events werereported in 82.0% (albiglutide) and 76.5% (placebo) of patients. Conclusion: In newly diagnosed patients with type 1 diabetes, albiglutide 30 to 50 mg weeklyfor 1 year had no appreciable effect on preserving residual ß-cell function versus placebo.