BACKGROUND: Our previous work has shown that senescent B cells accumulate in the human adipose tissue (AT) of people with obesity, where they express transcripts for markers associated with the senescence-associated secretory phenotype (SASP) and secrete multiple inflammatory mediators. These functions of AT-derived B cells are metabolically supported. OBJECTIVES: To show that Metformin (MET), a widely used hypoglycemic and antidiabetic drug, is able at least in vitro to decrease frequencies, secretory profile, and metabolic requirements of senescent B cells isolated from the AT of people with obesity. METHODS: We recruited adult females with obesity (n = 8, age 40 ± 2 y, BMI range: 33-42) undergoing breast reduction surgery, who donated their discarded subcutaneous AT. B cells from stromal vascular fractions isolated after collagenase digestion of the AT were evaluated after in vitro incubation with MET (1 mM × 10 RESULTS: MET in vitro was able to reduce frequencies and numbers of senescent B cells, as identified by staining with β-galactosidase, as well as the secretion of inflammatory cytokines, the expression of transcripts for SASP, and metabolic markers that support intrinsic B cell inflammation. CONCLUSIONS: Our results provide evidence to support the beneficial effects of MET in reducing AT-related inflammation through its effects on senescent B cells.