Case Report: Dramatic metabolic improvement with tirzepatide in a patient with acquired partial lipodystrophy following hematopoietic stem cell transplantation.

BACKGROUND

Acquired lipodystrophy is a rare disorder characterized by adipose tissue loss or dysfunction and is frequently associated with severe insulin resistance and metabolic complications. Metabolic complications of lipodystrophy have occasionally been reported after hematopoietic stem cell transplantation (HSCT), but their clinical features and optimal treatment strategies remain poorly defined. Tirzepatide, a dual agonist of the glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors, has recently emerged as a novel therapy for type 2 diabetes.

CASE PRESENTATION: We report a 37-year-old woman who underwent allogeneic HSCT at 12 years of age for relapsed acute lymphoblastic leukemia after a conditioning regimen including total body irradiation (TBI), high-dose cytarabine, and melphalan. She subsequently developed diabetes mellitus and fatty liver disease at 17 years of age. Although no apparent fat loss was initially recognized, lipodystrophy was clinically suspected based on severe insulin resistance and metabolic abnormalities disproportionate to her body habitus. Computed tomography at 37 years of age revealed region-specific fat loss extending from the lower back to the gluteal region. Glycemic control remained inadequate despite high-dose insulin therapy and sequential treatment with several GLP-1 receptor agonists. After initiation of tirzepatide, glycemic control improved dramatically, allowing complete discontinuation of insulin therapy. Body weight decreased modestly and hepatic steatosis improved. The high-molecular-weight (HMW)/total adiponectin ratio after treatment was elevated (64.0%), suggesting possible improvement in adipocyte secretory function.

CONCLUSION

This case highlights acquired partial lipodystrophy developing after HSCT, supported by region-specific fat loss and characteristic metabolic abnormalities, and demonstrates a marked therapeutic response to tirzepatide. Dual incretin receptor agonism may represent a promising therapeutic strategy for severe insulin resistance associated with adipose tissue dysfunction, potentially through both weight-dependent and weight-independent mechanisms.