Anti- and non-tumor necrosis factor-α-targeted therapies effects on insulin resistance in rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis

Table 3 Studied effects on diabetes mellitus by applying anti-tumor necrosis factor- and non-tumor necrosis factor- targeted agents for treating patients with rheumatology disorders

No.	Source	Drug	Mechanism	PN	Clinical feature(s)	Duration	Effect on IR or diabetic status	Ref.
1	2005, United States	ETA	rSTNFRFP	10	Type II DM, obese	4 wk	Ineffective IS	[147]
2	2007, INC	ANA	IL-1Ra	34	Type II DM	13 wk	Reduced HbA1C and increased insulin secretion at 13 wk, reduced insulin doses at 39 wk	[156]
3	2009, United States	RTX	CD20 mAb	49	Type I DM, recent	1 yr	Reduced HbA1C/insulin doses and higher 2 h C-peptide AUC at 1 yr, no differences at 30 mo	[150]
4	2011, United States	ABA	CTLA4-Ig	73	Type I DM, recent	2 yr	Higher 2 h C-peptide AUC	[155]
5	2011, United States	TNFi	ETA, IFX	8	Type II DM	10 yr	Reduced HbA1C and fasting glucose levels	[148]
6	2011, Japan	TCZ	IL-6R mAb	10	Type II DM	6 mo	Reduced HbA1C and use of antidiabetic drugs	[110]
7	2012, INC	CAN	IL-1 mAb	151	Type II DM	4 wk	Increased insulin secretion (ISR relative to glucose at 0 to 0.5 h)	[157]
8	2012, INC	CAN	IL-1 mAb	372	Type II DM	4 mo	Ineffective HbA1C, fasting glucose and insulin levels	[158]
9	2012, INC	GEV	IL-1 mAb	81	Type II DM	13 wk	Reduced HbA1C, increased IS and insulin secretion at single i.v. groups (0.03, 0.1 mg/kg)	[159]
10	2013, INC	ANA	IL-1 Ra	25	Type I DM, recent	9 mo	Ineffective 2 h C-peptide AUC	[160]
11	2013, INC	CAN	IL-1 mAb	45	Type I DM, recent	I yr	Ineffective 2 h C-peptide AUC	[160]
12	2014, INC	CAN	IL-1 mAb	14	Type II DM	24 wk	Reduced HbA1C at single i.v. 1.5 and 10 mg/kg groups	[161]
13	2015, Netherlands	ANA	IL-1Ra	14	Type I DM	1 wk	Reduced HbA1C, insulin doses and fasting glucose levels, increased IS	[162]
14	2015, Italy	ANA	IL-1Ra	2	Type II DM	6 mo	Reduced HbA1C and fasting glucose levels, reduced or off antidiabetic therapeutics	[145]
15	2015, Italy	ANA	IL-1Ra	3	Type II DM	6 mo	Reduced HbA1C and fasting glucose levels	[146]
16	2015, Germany	BER	IL-1 mAb	7	Type II DM	60 d	Increased insulin secretion	[163]
17	2016, Switzerland	GEV	IL-1 mAb	15	Type I DM	1 yr	Ineffective 2-h C-peptide AUC	[164]
18	2016, Switzerland	CAN	IL-1 mAb	6	Type II DM	24 wk	Reduced HbA1C	[165]
19	2017, Japan	RTX	CD20 mAb	3	Type II DM, insulin RS	6-16 mo	Reduced HbA1C and insulin doses, disappearance of IR antibody	[151]
20	2018, United States	RIL	IL-1R-Ig	13	Type I DM, recent	26 wk	Higher 2 h C-peptide AUC	[166]
21	2019, Italy	ANA	IL-1Ra	17	Type II DM	6 mo	Reduced HbA1C	[167]
22	2019, Italy	ANA	IL-1Ra	15	Type II DM	6 mo	Increased IS, improved β-cell function, decreased glucagon levels	[168]
23	2020, United States	TOF	JAKi	634	Type I, II DM	9 mo	DM treatment (insulin/non-insulin) intensification lowest in using TOF	[178]

ABA: Abatacept; ADA: Adalimumab; ANA: Anakinra; AUC: Area under the curve; BER: Bermekimab; CAN: Canakinumab; DM: Diabetes mellitus; ETA: Etanercept; GEV: Gevokizumab; IFX: Infliximab (a TNF mAb); Ig: Immunoglobulin; INC: International countries; Insulin RS: Insulin resistance syndrome; IR: Insulin receptor; IS: Insulin sensitivity; ISR: Insulin secretion rate; i.v.: Intravenous; JAKi: Janus kinase inhibitor; mAb: Monoclonal antibody; PN: Patient numbers; Ra: Receptor antagonist; RIL: Rilonacept; rSTNFRFP: Recombinant soluble tumor necrosis factor-α receptor fusion protein; TCZ: Tocilizumab; TNFi: Tumor necrosis factor inhibitor; TOF: Tofacitinib; RTX: Rituximab; HbA1c: Hemoglobin A1c; IL: Interleukin.