Effect of metreleptin treatment in congenital generalized lipodystrophy: a retrospective analysis from the MENA region

PURPOSE: Congenital generalized lipodystrophy (CGL) is characterized by near-total loss of body fat, leptin deficiency, and severe metabolic complications. Clinical data show that metreleptin improves metabolic control in CGL; however, data from the Middle East and North Africa (MENA) is limited. We assessed the real-world effectiveness and safety of metreleptin in patients with CGL from this region. METHODS: We conducted a multicenter, retrospective chart review of patients with CGL. Baseline, 6 ± 2months (short-term), 2 ± 1years (long-term), and >3 years follow-up data were analyzed. Median changes from baseline were calculated for short- and long-term assessments; >3 years data were reviewed individually. Safety was evaluated up to 90 days after last dose. RESULTS: Thirty-eight patients were included (82% female; median age at baseline, 6.3 years). Median treatment duration with metreleptin was 25 months (max dose, 10 mg/day). Significant short-term median reductions from baseline were observed for HbA1c (- 1.4%; n = 26), fasting plasma glucose (- 0.5 mmol/L; n = 21); fasting triglycerides (TG; -1.5 mmol/L; n = 26), alanine aminotransferase (- 18 IU/L, n = 27) and aspartate aminotransferase (- 7 IU/L, n = 27) (all p ≤ 0.02). These reductions were significant at long-term follow-up (p < 0.01) except for aspartate aminotransferase. At short-term follow-up, 50.0% of patients achieved ≥1% reduction in HbA1c and 65.4% had a ≥30% reduction in TG; corresponding long-term patient proportions were 46.7% and 61.5%. Most patients with >3 years follow-up showed improvement/maintenance of metabolic parameters. Overall, metreleptin was well tolerated with no new safety signals detected. CONCLUSIONS: Our findings support early intervention with metreleptin for sustained diabetes and hypertriglyceridemia control in CGL.