Unmasking Silent Lipomatosis: A Reversible Adverse effect of PPAR-γ Agonist Therapy

Abstract

Adipocytes develop from resident preadipocytes or bone marrow-derived progenitor cells, with peroxisome proliferator-activated receptor gamma (PPAR-γ) serving as a key regulator of adipogenesis. It promotes the expression of genes involved in lipid and glucose metabolism, fatty acid storage, and fat redistribution from visceral to subcutaneous depots. These processes may contribute to the development of lipomatosis, a condition characterized by abnormal and diffuse adipose tissue proliferation. Pioglitazone, a thiazolidinedione (TZD) and potent PPAR-γ agonist, is commonly prescribed to improve insulin sensitivity in patients with type 2 diabetes. A 68-year-old woman with type 2 diabetes, hyperlipidemia, and psoriasis developed progressive, painless fat accumulation in her upper arms, thighs, and buttocks after two years of alogliptin/pioglitazone combination therapy. A skin biopsy confirmed the diagnosis of lipomatosis. Following the discontinuing of pioglitazone and switching to a sodium-glucose cotransporter 2 (SGLT2) inhibitor, the fat deposits gradually regressed, as evidenced by a reduction in waist and extremity circumference over nine months. PPAR-γ agonist-induced lipomatosis is a rare but reversible adverse effect. Clinicians should recognize this possibility during long-term PPAR-γ agonist therapy and consider early discontinuation to facilitate fat regression.