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| Author, reference | Type of study and study duration | Drug | Patients/subjects | Main findings |
|
| Ofei et al., 1996 [86] | Double-blind clinical trial (8 weeks) | Engineered human anti-TNF-α antibody (CDP571) | Obese patients with T2D | No effect on insulin sensitivity |
| Paquot et al., 2000 [88] | Single-center, single-blind, sequential treatment (placebo, followed by active drug) study (6 days) | TNF-α antagonist: Ro 45-2081 (a recombinant fusion protein that consists of the soluble TNF-receptor p55 linked to the fc portion of human IgG1); single intravenous administration | Obese insulin-resistant patients | No effect on insulin sensitivity |
| Kiortsis et al., 2005 [87] | Clinical prospective study (6 months) | Anti-TNF-α (infliximab) | Insulin-resistant patients with rheumatoid arthritis and ankylosing spondylitis | In the entire study group, no significant changes of the HOMA index or QUICKI were observed. In the tertile of patients with the highest degree of insulin resistance, a significant decrease of the HOMA index and increase of the QUICKI was found |
| Dominguez et al., 2005 [89] | Parallel-group open-label randomized trial (4 weeks) | Anti-TNF-α (etanercept) | Obese patients with T2D | No effect on insulin sensitivity, increased insulin secretion |
| Bernstein et al., 2006 [90] | Double-blind, randomized controlled trial (4 weeks) | Anti-TNF-α (etanercept) | Patients with metabolic syndrome | No effect on insulin sensitivity, increased adiponectin levels |
| Lo et al., 2007 [60] | Randomized controlled trial (4 weeks) | Anti-TNF-α (etanercept) | Patients with metabolic syndrome | Decrease in glucose levels and HbA1c values, increased adiponectin levels |
| Larsen et al., 2007 [33] | Double-blind, parallel-group, randomized controlled trial (13 weeks) | Anti-IL-1 receptor antagonist (anakinra) | Patients with T2D | Reduced HbA1c values, increased insulin secretion, improved glycemia and beta-cell secretory function |
| Larsen et al., 2009 [80] | Double-blind, 39-week follow-up study | Anti-IL-1 receptor antagonist (anakinra) | Patients with T2D | Increased insulin secretion, decreased insulin requirements |
| van Asseldonk et al., 2011 [81] | Randomized, placebo-controlled trial (4 weeks) | Anti-IL-1 receptor antagonist (anakinra) | Nondiabetic, obese subjects with metabolic syndrome | Increased disposition index, improved insulin secretion, no effect on insulin sensitivity |
| Stanley et al., 2011 [59] | Randomized controlled trial (6 months) | Anti-TNF-α (etanercept) | Obese subjects with features of the metabolic syndrome | Decreased fasting glucose levels and HbA1c values, increased ratio of high molecular weight adiponectin to total adiponectin |
| Cavelti-Weder et al., 2012 [73] | Randomized, placebo-controlled trial (3 months) | Anti-IL-1β (gevokizumab) | Patients with T2D | Reduced HbA1c values, increased insulin secretion |
| Rissanen et al., 2012 [77] | Randomized, placebo-controlled trial (4 weeks) | Anti-IL-1β (canakinumab) | Patients with T2D and impaired glucose tolerance | Trend towards increased insulin secretion rate |
| Ridker et al., 2012 [82] | Randomized, placebo-controlled multinational phase IIb trial (5 months) | Anti-IL-1β (canakinumab) | Well-controlled T2D patients with high cardiovascular risk | No changes in HbA1c values, glucose, and insulin levels |
| Stagakis et al., 2012 [20] | Clinical prospective study (12 weeks) | Anti-TNF-α agents (infliximab, adalimumab, etanercept) | Patients with rheumatoid arthritis | Anti-TNF therapy improved insulin sensitivity and reversed defects in the insulin signaling cascade in patients with active disease and high insulin resistance |
| Hensen et al., 2013 [78] | Randomized, placebo-controlled trial (4 months) | Anti-IL-1β (canakinumab) | Patients with T2D | Reduced HbA1c values, nonsignificant increase in insulin secretion |
| Sloan-Lancaster et al., 2013 [74] | Phase II, randomized, double-blind, parallel, placebo-controlled study (12 weeks) | Neutralizing IL-1β antibody (LY2189102) | Patients with T2D | LY2189102 modestly reduced HbA1c values and fasting glucose levels |
| van Popper et al., 2014 [79] | Randomized, double-blind, placebo-controlled, crossover study (8 weeks) | Anti-IL-1 receptor antagonist (anakinra) | Subjects with impaired glucose tolerance | Improved insulin secretion (first-phase insulin secretion), improved insulinogenic index |
| Burska et al., 2015 [84] | Systematic review and meta-analysis | TNF-α inhibitors | Patients with rheumatoid arthritis | TNF inhibition therapy improved insulin sensitivity and reduced insulin resistance |
| Everett et al., 2018 [19] | Randomized, double-blind, placebo-controlled trial (3 months) | Anti-IL-1β (canakinumab) | Subjects with T2D, prediabetes and normal glucose tolerance | Canakinumab reduced HbA1c values during the first 6 to 9 months of treatment, but no consistent long-term benefits on HbA1c or fasting plasma glucose were observed |
| Kataria et al., 2019 [21] | Meta-analysis of 2921 individuals from eight phase I-IV studies | Anti-IL-1 therapies | Patients with T2D | Reduced HbA1c values |
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