Long-Term Clinical Experience With Metreleptin in a Brazilian Patient With Congenital Generalized Lipodystrophy Type...

We describe our 8-year clinical experience with metreleptin in a Brazilian adult female patient with congenital generalized lipodystrophy type 2 (due to a mutation in the BSCL2 gene) and severe insulin resistance. The patient was initially treated with antidiabetic medications due to the unavailability of metreleptin. Metreleptin was initiated at age 20 years. Reductions from baseline for glycated hemoglobin (HbA1c) and triglycerides on metreleptin were sustained over a 5-year treatment period. The greatest reductions in HbA1c (from 10.8% [95 mmol/mol] to 6.0% [42 mmol/mol], -4.8%) and triglycerides (from 398 mg/dL [4.5 mmol/mL] to 104 mg/dL [1.2 mmol/L], -74%) occurred after 39 months, accompanied by a -95% decrease in total daily insulin usage (from 1600 to 88 IU/day). No significant adverse events occurred throughout metreleptin therapy. Metreleptin therapy was interrupted for 36 months due to limited access to the medication, during which time metabolic parameters deteriorated, returning to near-baseline levels. Thereafter, metreleptin was restarted. At the most recent clinic evaluation (3 months after resuming metreleptin), HbA1c, triglycerides, and liver enzyme levels reduced relative to the last measurements taken during treatment interruption. These findings provide support for the long-term and continuous use of metreleptin in patients with generalized lipodystrophy.