Liraglutide use in congenital generalized lipodystrophy: glycemic and metabolic outcomes.

Objective: Evidence on glucagon-like peptide 1 receptor agonists (GLP-1RAs) in lipodystrophies is limited. We evaluated the effects of liraglutide on metabolic control and satiety in patients with congenital generalized lipodystrophy (CGL). Methods: In this case series, patients with CGL received liraglutide 1.8 mg/day for 12 weeks. Metabolic parameters, satiety, and body composition were assessed at baseline, week 12, and after a 12-week post-treatment follow-up (week 24). Liver imaging was performed at baseline and week 12. Results: Eight patients were enrolled (aged 24-45 years; 75% female), and three discontinued treatment due to gastrointestinal adverse events during the dose-escalation phase. Among the five participants who completed the 12-week intervention, liraglutide significantly reduced HbA1c (median change, -2.5%; p=0.012) and total daily insulin dose (-20%; p=0.042), whereas the reduction in triglyceride levels was not statistically significant. Twelve weeks after liraglutide discontinuation, median HbA1c and body weight increased by 2.2% (p=0.026) and 3.7% (p=0.001), respectively. Triglyceride levels increased in 80% of participants, with a median increase of 421.5 mg/dL (p=0.334). Insulin requirements also increased overall: one participant resumed insulin therapy, while the remaining participants increased their insulin dose by a median of 22% (p=0.024). Conclusions: This first study of liraglutide in CGL provides an exploratory signal of improved glycemic control and reduced insulin requirements, but treatment tolerability remains a limitation. Larger, controlled, and longer-term studies are needed to confirm these effects and assess potential benefits on satiety, body composition, and liver disease.