Safety and efficacy of teplizumab in the treatment of type 1 diabetes mellitus: An updated systematic review and meta‐analysis of randomized controlled trials

• Published in: Diabetes, obesity & metabolism Vol. 26; no. 7; pp. 2652 - 2661
• Main Authors: Grando Alves, Gabriel, Cunha, Luisa, Henkes Machado, Rafael, Lins de Menezes, Vanessa
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.07.2024; Wiley Subscription Services, Inc
• Subjects: Adverse events; anti‐CD3 monoclonal antibody; Clinical trials; C‐peptide; Diabetes; Diabetes mellitus (insulin dependent); Hemoglobin; Insulin; Meta-analysis; Monoclonal antibodies; Peptides; Statistical analysis; Statistics; systematic review; T1DM; teplizumab; type 1 diabetes mellitus; T1DM; teplizumab; type 1 diabetes mellitus; meta‐analysis; systematic review; C‐peptide; anti‐CD3 monoclonal antibody
• ISSN: 1462-8902; 1463-1326; 1463-1326
• DOI: 10.1111/dom.15581

Aim To provide updated efficacy and safety information for teplizumab in the treatment of Stage 3 type 1 diabetes mellitus (T1DM). Materials and Methods The PubMed, Embase and Cochrane databases were searched for randomized controlled trials (RCTs) comparing teplizumab to placebo for T1DM that reported any of the following outcomes: (1) C‐peptide area under the curve (AUC); (2) glycated haemoglobin (HbA1c) levels; (3) insulin requirements; and (4) adverse events. Heterogeneity was examined with I2 statistics. p values <0.05 were taken to indicate statistical significance. The continuous endpoints were compared through the pooled mean difference (MD) and binary endpoints were assessed using risk ratios, both with 95% confidence intervals (CIs). Statistical analyses were performed using Review Manager Web software. Results Eight RCTs with 1052 patients (754 receiving teplizumab) were included. Teplizumab significantly increased the AUC of C‐peptide levels at 6 (MD 0.10 nmol/L, 95% CI 0.05, 0.16), 12 (MD 0.13 nmol/L, 95% CI 0.06, 0.20), 18 (MD 0.18 nmol/L, 95% CI 0.09, 0.27) and 24 months (MD 0.16 nmol/L, 95% CI 0.02, 0.31), significantly reduced HbA1c levels at 6 (MD −0.57%, 95% CI −1.07, −0.08) and 12 months (MD −0.31%, 95% CI −0.59, −0.02), and significantly reduced insulin requirements at 6 (MD −0.12 U/kg, 95% CI −0.16, −0.08), 12 (MD −0.11 U/kg, 95% CI −0.15, −0.07), 18 (MD −0.17 U/kg, 95% CI −0.26, −0.09) and 24 months (MD −0.11 U/kg, 95% CI −0.22, −0.01). Conclusion Teplizumab increases AUC of C‐peptide levels and decreases HbA1c levels and insulin use, without raising serious adverse event risk.