Randomized 52-week Phase 2 Trial of Albiglutide Versus Placebo in Adult Patients With Newly Diagnosed Type 1 Diabetes

Abstract

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 to 50 mg at week 6) versus placebo together with insulin in patients with new-onset type 1 diabetes 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 change from baseline in mixed meal tolerance test (MMTT) stimulated 2-h plasma C-peptide area under the curve (AUC). Secondary endpoints included metabolic measures and pharmacokinetics of albiglutide. Results 12/17 (70.6%, placebo) and 40/50 (80.0%, albiglutide) patients completed the study. Within our study, mean (standard deviation) change from baseline to week 52 in MMTT-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 study data) 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 were reported in 82.0% (albiglutide) and 76.5% (placebo) of patients. Conclusion In newly diagnosed patients with type 1 diabetes, albiglutide 30 to 50 mg weekly for 1 year had no appreciable effect on preserving residual β-cell function versus placebo.

Anti-interleukin-21 antibody and liraglutide for the preservation of β-cell function in adults with recent-onset type 1 diabetes: a randomised, double-blind, placebo-controlled, phase 2 trial

“…20,21 Thus, liraglutide might, in addition to evidently preserving glucose-induced insulin secretion under immune stress, also directly preserve beta-cell health. Of note, however, another GLP-1 RA, albiglutide, did not preserve β-cell function (vs placebo) during a recent 1-year trial in newly diagnosed T1D 33 . To elucidate these important aspects, additional studies are needed, likely on organoids because no human in vivo beta-cell mass assessments are currently available.…”

Glucose-Lowering Therapy beyond Insulin in Type 1 Diabetes: A Narrative Review on Existing Evidence from Randomized Controlled Trials and Clinical Perspective

“…Albiglutide: In a study including 67 participants with newly diagnosed T1D, albiglutide administered once a week for one year had no appreciable effect on β-cell function, HbA 1c and weight in newly diagnosed individuals with T1D when compared to placebo [71]. Anyway, albiglutide was withdrawn from the market in 2018.…”

Beta Cell Therapies for Preventing Type 1 Diabetes: From Bench to Bedside

“…The question of whether beta cell function can be improved in T1D by repurposing T2D drugs remains open. However recent studies targeting glucagon-like peptide 1 (GLP-1) and GLP-1 receptor (GLP1R) signaling suggest that this may not be effective (NCT01155284, NCT02284009) [67,68]. As future studies begin to understand the points at which beta cells are most vulnerable to ER stress-induced functional decline and terminal UPR during the various stages of T1D development, it may be possible to use these therapies intermittently and when they are most needed, obviating the side-effects resulting from chronic daily administration.…”