Janus Kinase Inhibitors and Body Weight: Current Evidence and Potential

Janus kinase (JAK) inhibitors have become an important therapeutic option for a wide range of immune-mediated inflammatory diseases. By targeting intracellular cytokine signaling through inhibition of the JAK-STAT pathway, these agents provide effective suppression of multiple inflammatory cascades. Alongside their growing clinical use, changes in body weight-particularly weight gain-have recently been reported in clinical practice. Although this phenomenon has not consistently emerged as a prominent adverse event in randomized clinical trials, observational studies and real-world data suggest that weight gain may occur in some of the treated patients. The mechanisms underlying these changes remain barely understood and are likely multifactorial. Effective suppression of systemic inflammation may reverse inflammation-driven catabolism and restore metabolic balance, contributing to increases in body weight and lean body mass. In addition, experimental evidence indicates that JAK-STAT signaling participates in adipocyte differentiation, lipid metabolism, and energy regulation. Pharmacologic inhibition of this pathway may therefore influence adipose tissue biology, thermogenic activity, and appetite regulation through leptin-dependent signaling pathways. This review summarizes current evidence regarding weight and body composition changes associated with JAK inhibitor therapy, integrating findings from experimental studies, clinical trials, and real-world observations. Potential biological mechanisms are discussed alongside patient-related and disease-related factors that may modify the risk of weight gain. A better understanding of these immune-metabolic interactions may help guide clinical monitoring and future research on the metabolic consequences of JAK inhibition.