Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by damage to multiple systems and a higher risk of cardiovascular disease. In addition, several studies have found that insulin resistance (IR) is more prevalent in SLE patients compared with controls, which increases the risk of prediabetes, type 2 diabetes mellitus (T2DM) and morbidity. The objective of this review was to summarize the most relevant evidence about the relationship among IR, T2DM and SLE, including the effects of pro-inflammatory states, acute-phase proteins, pro-inflammatory cytokines, and pharmacological SLE treatment. A better understanding of the mechanisms involved in these comorbidities will allow better treatment strategies.