Background: Despite advances in insulin therapy, metabolic outcomes in T1D remain suboptimal. Immunotherapy to preserve beta cell function has enormous potential but the metabolic benefits and the size of trial needed to demonstrate them remain unclear, hindering drug development.

Methods: Our dataset comprised 1315 adults and 1396 children enrolled in 20 immunotherapy intervention trials within 100 days of diagnosis. End points assessed were AUC c-peptide, HbA1c, IDAAC, Beta-2 Score and hypoglycemia. Differences in outcomes between active and control arms in positive and negative studies were assessed using the Wilcoxon rank test.

Results: C-peptide preservation in positive studies resulted in greater improvements in HbA1c within 3 months of beginning therapy. Beyond the initial 3 month “honeymoon” period, 20% greater preservation of C-peptide in active versus placebo subjects was associated with a 0.5% lower HbA1c. Higher initial C-peptide levels and greater C-peptide preservation were associated with better glycemic outcomes.

Sample size for HbA1c, IDAAC, and Beta-2 Score required 2-3 times as many subjects per armto demonstrate a difference at 6 months as compared to C-peptide. Smaller samples sizes were required in children. Longer studies are required to demonstrate durability but not efficacy. Hypoglycaemia rates required substantially larger sample sizes and more than 1 year follow-up.

Conclusion: Immunotherapy to preserve beta cell function is effective at improving metabolic outcomes in new-onset T1D. Beyond the initial 3 month period, improvements in HbA1c are proportional to C-peptide preservation. Early intervention and sustained high C-peptide levels are required for ongoing benefits.


P.Taylor: None. M.Rigby: None. P.Gottlieb: Advisory Panel; ViaCyte, Inc., Board Member; ImmunoMolecular Therapeutics, Research Support; Imcyse, Hemsley Charitable Trust, Novartis, National Institute of Diabetes and Digestive and Kidney Diseases, Precigen, Inc., Dompé, Nova Pharmaceuticals, Provention Bio, Inc. C.Dayan: Advisory Panel; AstraZeneca, Consultant; Provention Bio, Sanofi, Avotres Inc., Other Relationship; Dompé, Merck & Co., Inc. K.S.Collins: None. S.Karpen: None. E.Atabakhsh: None. S.Ahmed: None. M.Marinac: None. E.Latres: None. A.Lam: None. P.A.Senior: Advisory Panel; Novo Nordisk Canada Inc., Consultant; Novo Nordisk Canada Inc., Bayer Inc., Viatris Inc., Vertex Pharmaceuticals Incorporated, ViaCyte, Inc., Insulet Corporation.


JDRF; Diabetes UK

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