Table 1.

Non-insulin agents for the prevention and management of type 1 diabetes

Mechanism of action/target	Agent	Reference of selected main studies or ClinicalTrials.gov registration no.
Systemic approaches
T effector cells	Teplizumab (anti-CD3)	[27–29, 31]; NCT03875729
	Otelixizumab (anti-CD3)	[30]
	ATG	[36]
	Abatacept (anti-CD80 and anti-CD86)	[42, 43]
	Alefacept	[39]
	Anti-IL-21 antibody	[55, 56, 59, 61]
B cells	Rituximab (anti-CD20)	[34, 35]
T regulatory cell expansion	Low-dose IL-2	[44–48]
Anti-inflammation	Infliximab, adalimumab, etanercept, golimumab (anti-TNF-α)	[49–51]
	Tocilizumab (anti-IL-6R)	[53, 54]; NCT02293837
	GLP-1 RAs	[120–123]
Islet/beta cell-specific approaches
Islet-antigen tolerisation/immunisation	Oral insulin	[63–66]
	GAD65	[67]
	Peptides	[68, 69]
Beta cell stress relief and stimulation	GLP-1 RAs	[91, 92, 113–117, 135–138]
	Verapamil	[102, 103]
Cardiometabolic improvementsa
SGLT inhibition	Dapagliflozin, empagliflozin, sotagliflozin	[78–83, 88, 89]
GLP-1 agonism	Exenatide, liraglutide, dulaglutide, semaglutide	[90–92, 135–138]
Other/unspecific	Amylin (pramlintide)	[145, 146]
	Metformin	[73–76]

^aIncluding blood glucose levels, body weight, blood lipids, blood pressure and cardiorenal risk