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.