MON-694 Resolving the Metabolic Puzzle, Tirzepatide's Multifaceted Benefits in Partial Lipodystrophy

Abstract Disclosure: L.D. Barrett: None. R.J. Brown: None. Background: Lipodystrophy (LD) syndromes are a group of disorders characterized by selective deficiency of adipose tissue. LD is subclassified as generalized (GLD), in which essentially all adipose tissue is missing, or partial (PLD), in which large regions of adipose tissue (most often in the extremities) are absent. Both types lead to ectopic lipid deposition with resultant insulin resistance, and health consequences analogous to severe obesity despite low fat mass. Metreleptin is an approved therapy for GLD, but there are no FDA-approved treatments for PLD. Clinical Case: A 36-year old woman showed typical symptoms of LD with history of hypertriglyceridemia induced pancreatitis, high exogenous insulin requirement (150 units per day by Tandem T-slim pump), metabolic associated steatohepatitis, sleep apnea, and muscular features with lack of adipose tissue in limbs and was diagnosed with PLD. Medications included insulin, metformin XR 2000 mg daily, empagliflozin 25 mg daily, rosuvastatin 20 mg daily, icosapent ethyl 4 grams daily, and fenofibrate 160 mg daily. The patient was started on tirzepatide with slow uptitration. Within 24 hours of the first injection of 2.5 mg, the total daily dose of insulin decreased by 37%, from 150 to 94 units. Rapid changes in insulin requirement led to significant hypoglycemia and required correspondingly rapid pump adjustments. Within 5 months, while on tirzepatide 10 mg weekly, the patient was able to discontinue insulin altogether with continued monitoring of blood glucose by continuous glucose monitoring. A1c changed from 6.8 to 5.7%. Triglyceride decreased from 211 mg/dL to 73 mg/dL, despite discontinuation of fenofibrate. Liver fat as measured by fibroscan controlled attenuation parameter (CAP) decreased from 317 dB/m to 214 dB/m (normal 90-248). Additionally, there was profound (29%) weight loss with reduction in BMI from 31.6 to 22.4 kg/m2. Conclusion: The patient exhibited profound and multifaceted metabolic improvement following initiation of tirzepatide treatment. These improvements were much greater than previously reported with GLP-1 receptor agonists in PL, suggesting a unique role for GIP receptor agonism in addressing the complex metabolic dysregulation associated with this disorder. The observed clinical benefits, including improved glycemic control, triglyceride improvement, reduced insulin dependence, and improved steatosis have significant implications for the management of this complex and challenging condition. Further research is needed to confirm these findings and explore broader applicability of tirzepatide in this patient population. Presentation: Monday, July 14, 2025