Copyright ©The Author(s) 2021.
World J Diabetes. Mar 15, 2021; 12(3): 238-260
Published online Mar 15, 2021. doi: 10.4239/wjd.v12.i3.238
Table 1 Studies on effects of anti-tumor necrosis factor therapies on insulin resistance in non-diabetic rheumatoid arthritis patients
No.SourceCharacterCases, n, drug (s)Clinical feature (s)DurationEffects on IRRef.
12004, AustriamAb2 IFXNon-diabetic4 or 8 moImproved HOMA-IR only in high-IR group[67]
22005, GreecemAb28 IFXNon-diabetic6 moImproved HOMA-IR only in high-IR group[68]
32006, SpainmAb27 IFXNon-diabetic2 h after infusionImproved HOMA-IR[69]
42007, NetherlandsmAb5 IFXNon-diabetic6 wkImproved insulin sensitivity1[70]
52007, DenmarkmAb9 ADANon-diabetic, high IR8 wkIneffective HOMA-IR[71]
62007, ChinamAb19 IFXNon-diabetic14 wkImproved HOMA-IR[72]
72007, TurkeymAb7 IFXNon-diabetic5-15 moImproved HOMA-IR[73]
82008, SpainmAb21 IFXNon-diabetic24 wkImproved HOMA-IR[74]
92008, ItalymAbs, sTNFRFP, Mixed20 ETA, 18 IFX, Total 38Non-diabetic24 wkImproved HOMA-IR[63]
102011, SpainmAbs, rsTNFRFP, Mixed8 ADA, 6 IFX, 2 ETA, Total 16Non-diabetic12 moIneffective HOMA-IR[64]
112012, United KingdommAbs, rsTNFRFP, Mixed49 IFX, 11 ADA, 1 ETA, Total 61Non-diabetic12 wkImproved HOMA-IR in high-IR group[65]
122012, GreecemAbs, rsTNFRFP, Mixed20 IFX, 11 ETA, 1 ADA, Total 32Non-diabetic6 moImproved HOMA-IR in high-IR, non-obese group[66]
132019, ItalymAbs, rsTNFRFP, Separated11 IFX, 12 ETA, 10 ADA, Total 33Non-diabetic, non-obese24 wkImproved HOMA-IR in individual group of all TNF blockers[75]
142020, NetherlandsmAb28 ADANon-diabetic6 moIneffective HOMA-IR, improved-β-cell function[76]
152020, TaiwanrsTNFRFP30 ETANon-diabetic, non-obese24 wkImproved HOMA-IR in high-IR group[77]
Table 2 Studies on effects of non-tumor necrosis factor-targeted therapies on insulin resistance in rheumatoid arthritis patients
No.SourceDrugCases, nClinical featuresDurationEffects on IRRef.
12010, GermanyTCZ11Non-diabetic3 moImproved HOMA-IR[116]
22012, United KingdomABA7Non-diabetic, active disease12 wkIneffective HOMA-IR[65]
32013, United KingdomTCZ221Active disease24 wkImproved HOMA-IR[117]
42013, United KingdomTCZ62Active disease, JRA children6 wkImproved HOMA-IR in high-IR group[118]
52015, ItalyABA15Non-diabetic, active disease6 moImproved ISI, ineffective β-cell functions[119]
62015, TaiwanTCZ24Active disease24 wkImproved HOMA-IR[120]
72015, GreeceTCZ19Active disease6 moIneffective HOMA-IR[121]
82017, FranceTCZ15Active disease6 moIneffective HOMA-IR[122]
92019, SpainTCZ50Non-diabetic1 h after 1st infusionImproved HOMA-IR[123]
102019, FranceOther1, TNFi107, 96Active disease24 wkImproved leptin/adiponectin ratios in other group than TNFi group[124]
112020, FranceTCZ77Active disease12 moIneffective HOMA-IR[125]
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.SourceDrugMechanismPNClinical feature(s)DurationEffect on IR or diabetic statusRef.
12005, United StatesETArSTNFRFP10Type II DM, obese4 wkIneffective IS[147]
22007, INCANAIL-1Ra34Type II DM13 wkReduced HbA1C and increased insulin secretion at 13 wk, reduced insulin doses at 39 wk[156]
32009, United StatesRTXCD20 mAb49Type I DM, recent1 yrReduced HbA1C/insulin doses and higher 2 h C-peptide AUC at 1 yr, no differences at 30 mo[150]
42011, United StatesABACTLA4-Ig73Type I DM, recent2 yrHigher 2 h C-peptide AUC[155]
52011, United StatesTNFiETA, IFX8Type II DM10 yrReduced HbA1C and fasting glucose levels[148]
62011, JapanTCZIL-6R mAb10Type II DM6 moReduced HbA1C and use of antidiabetic drugs[110]
72012, INCCANIL-1 mAb151Type II DM4 wkIncreased insulin secretion (ISR relative to glucose at 0 to 0.5 h)[157]
82012, INCCANIL-1 mAb372Type II DM4 moIneffective HbA1C, fasting glucose and insulin levels[158]
92012, INCGEVIL-1 mAb81Type II DM13 wkReduced HbA1C, increased IS and insulin secretion at single i.v. groups (0.03, 0.1 mg/kg)[159]
102013, INCANAIL-1 Ra25Type I DM, recent9 moIneffective 2 h C-peptide AUC[160]
112013, INCCANIL-1 mAb45Type I DM, recentI yrIneffective 2 h C-peptide AUC[160]
122014, INCCANIL-1 mAb14Type II DM24 wkReduced HbA1C at single i.v. 1.5 and 10 mg/kg groups[161]
132015, NetherlandsANAIL-1Ra14Type I DM1 wkReduced HbA1C, insulin doses and fasting glucose levels, increased IS[162]
142015, ItalyANAIL-1Ra2Type II DM6 moReduced HbA1C and fasting glucose levels, reduced or off antidiabetic therapeutics[145]
152015, ItalyANAIL-1Ra3Type II DM6 moReduced HbA1C and fasting glucose levels[146]
162015, GermanyBERIL-1 mAb7Type II DM60 dIncreased insulin secretion[163]
172016, SwitzerlandGEVIL-1 mAb15Type I DM1 yrIneffective 2-h C-peptide AUC[164]
182016, SwitzerlandCANIL-1 mAb6Type II DM24 wkReduced HbA1C[165]
192017, JapanRTXCD20 mAb3Type II DM, insulin RS6-16 moReduced HbA1C and insulin doses, disappearance of IR antibody[151]
202018, United StatesRILIL-1R-Ig13Type I DM, recent26 wkHigher 2 h C-peptide AUC[166]
212019, ItalyANAIL-1Ra17Type II DM6 moReduced HbA1C[167]
222019, ItalyANAIL-1Ra15Type II DM6 moIncreased IS, improved β-cell function, decreased glucagon levels[168]
232020, United StatesTOFJAKi634Type I, II DM9 moDM treatment (insulin/non-insulin) intensification lowest in using TOF[178]
Table 4 Studies and case reports on effects of anti-tumor necrosis factor and non-tumor necrosis factor-targeted therapies on insulin resistance or diabetes in ankylosing spondylitis and psoriatic arthritis/psoriasis patients
No.SourceDrugCase, n diseaseClinical feature(s)DurationEffect on IR or DM statusRef.
12005, GreeceIFX17, ASNon-DM6 moReduced HOMA-IR in high-IR group[68]
22007, ItalyETA9, PsONon-DM24 wkReduced HbA1C and insulin levels[188]
32009, BrazilETA1, PsOType II DM7 hHypoglycemic episode[189]
42009, United StatesETA1, PsOType II DM20 moReduced HbA1C and fasting glucose levels, discontinuing insulin use[190]
52010, BrazilTNF blocker118, PsANon-DM6 moNo changes in fasting glucose levels[191]
62010, BrazilTNF blocker137, ASNon-DM6 moNo changes in fasting glucose levels[191]
62011, United StatesADA54, PsODM 13%, PsA 41%16 wkIneffective changes in fasting glucose levels in DM[192]
72012, SpainIFX30, ASNon-DM120 minReduced HOMA-IR[196]
82014, TurkeyIFX30, ASNon-DM12 wkIneffective HOMA-IR[197]
92017, United StatesETA1, PsAType II DM, obesity12 wkReduced HbA1C and fasting glucose levels, discontinuing insulin use[193]
102018, TaiwanUST93, PsOObesity 45%24 wkIncreased fasting glucose levels[207]
112018, United StatesIXE2328, PsODM 9%, PsA 24%12 wkNo changes in fasting glucose levels[202]
122019, GermanySEC828, PsODM 10%, PsA 19%52 wkNo changes in fasting glucose levels[204]
132019, INCAPR1089, PsA/ODM 9%52 wkReduced HbA1C, improvement highest in HbA1C no less than 6.5%[210]
142019, ItalyAPR1, PsOType II DM, obesity6 moReduced HbA1C and fasting glucose levels, discontinuing insulin use[211]
152020, ItalyAPR113, PsA/ODM, 25%52 wkReduced fasting glucose levels[212]
162020, INCTOF474, PsAMetS, 42%6 moNo increased blood glucose levels, hyperglycemic event and diabetic occurrence[217]
172021, TaiwanTOF5, PsANon-DM, non-obese, high-IR12 wkReduced HOMA-IRPS