Being the leading cause of mortality by a single infectious agent, tuberculosis (TB) continues as one of the most relevant issues of public health. Another pandemic disease is type 2 diabetes mellitus (T2D) is usually associated with immunodeficiency. Thus, an increased prevalence of TB-T2D comorbidity represents one of the most significant challenges for health providers. During the chronic phase of both diseases, several immunoendocrine abnormalities are occurring, but extra-adrenal production of active glucocorticoids (GCs) is a possible deleterious factor in both entities. Active GCs have been related to insulin resistance and suppression of Th1 responses, contributing to T2D and TB pathogenesis. 11-β-hydroxysteroid dehydrogenase type 1 (11-βHSD1) catalyzes the conversion of inactive GGs in their active form (cortisol or corticosterone in rodents) in the lungs and liver and could be responsible for this immunoendocrine disfunction. Dehydroepiandrosterone (DHEA) is an anabolic adrenal hormone with antagonist effects against GCs on immune cells and glucose metabolism. A synthetic analog of DHEA, the 16abromoepindrosterone (BEA), lacks an anabolic effect while keeping his immune and metabolic effect. The therapeutic efficiency of BEA was studied in a murine model of T2D-TB comorbidity. TB-T2D mice underwent more severe lung disease than in TB-infected but non-diabetic animals. BEA decreased the active form of GCs and 11-βHSD1 expression, while increasing 11-βHSD2 expression, which reduced hyperglycemia and liver steatosis, lung bacillary loads, and pneumonia. Thus, it seems that BEA is an efficient therapy to control metabolic and immune abnormalities caused by high active GCs production.