In patients with rheumatoid arthritis, the cardiovascular risk is more than doubled, compared to the healthy population. Chronic inflammatory status leads to an intensification of the atherosclerotic process, resulting in a higher susceptibility to hypertension, obesity, and metabolic syndrome. The overproduction of IL-6 is strictly related to lipid profile alterations, given its role in adipose tissue lipolysis. The inflammation and endothelial damage are exacerbated by leptin production. Batun-Garrido, Salas-Magana and Juarez-Rojop [79] found a significant correlation between HCQ treatment and lower IL-6 and leptin levels. The positive effect of HCQ on dyslipidemia was also confirmed by Morris, Wasko, Antohe, Sartorius, Kirchner, Dancea and Bili [80] in a cohort study involving 706 rheumatoid arthritis diagnosed patients, finding a significant and stable cholesterol-lowering, mainly Low-Density Lipoprotein (LDL), and triglyceride decrease associated with HCQ intake (6.5 mg/kg/day). A small but statistically significant amelioration in total cholesterol and LDL under HCQ treatment at the same dosage was also highlighted by a randomized, double-blind cross-over trial on patients with rheumatoid arthritis [81]. The correlation between HCQ and cardiovascular risk was also assessed in a cross-sectional observational study involving 177 women with rheumatoid arthritis. At doses of 200 mg/kg/day, HCQ usage led to lower fasting glucose in women, arising as a valuable tool to enhance glycemic control [82]. However, apparent different outcomes were derived from a randomized double-blind crossover trial, recruiting 23 non-diabetic subjects with stable rheumatoid arthritis to receive 6.5 mg/kg/day of HCQ for eight weeks. For these patients, no significant changes in insulin resistance were observable [81]. This study evaluated only insulin sensitivity, by Homeostatic Model Assessment (HOMA) index, without considering insulin metabolism. Thus, inconsistency should be explained by this factor, together with the short duration of treatment. The anti-diabetic properties of HCQ have been also assessed in patients without arthritis, as reported in the next paragraphs.