Table 1: Representative Clinical Trials of Anti-inflammatory Treatments on Type 1 Diabetes.

Mechanism of action	Drug	Main findings	References
Monoclonal anti-CD20 antibody	Rituximab	Rate of C peptide decline ↓, lower insulin requirements, HbA1c ↓	49,50
Engineered DNA plasmid encoding proinsulin	BHT-3021	↓ CD8+ T cells frequency reactive to proinsulin, C peptide preservation, no change to Interferon-gamma, IL-4, IL-10	51
Proinsulin peptide	Human leukocyte antigen-DR4 (DRB1*0401)	↑ C-peptide, ↑ proinsulin-stimulated IL-10 production, favourable beta-cell stress markers (proinsulin/C-peptide ratio)	189
TNF antagonism	Etarnecept	HbA1c ↓, endogenous insulin production ↑	53
Anti-inflammatory serum protein	Alpha 1 antitrypsin (AAT)	IL-1beta response to monocytes and dendritic monocytes ↓, beta-cell function improvement	54
Vitamin D analogue	Alfacalcidol	Beta-cell preservation especially in male subjects	56
Vitamin D analogue	Calcitriol	↑ in fasting C peptide from diagnosis to 1 year, daily insulin dose ↓ in the treatment group	190
IL-1 receptor blockade	Anakinra	No C peptide response	58
IL-1 receptor blockade	Anakinra	↓ insulin requirements compared with controls, ↓ insulin dose adjusted	191
IL-1beta antagonism	Canakinumab	No C peptide response	58
IL-1 receptor blockade IL-1beta antagonism (plasma-induced transcriptional meta-analysis)	Anakinra/canakinumab	Immunomodulation/reverse relationship between inflammation and C peptide stimulation	192
ALPHAti-CD3 mAbs	Teplizumab/otelixizumab		52

CD20 = cluster of differentiation 20, IL = interleukin, mAbs = monoclonal antibodies, TNF = tumour necrosis factor.