Liraglutide use in congenital generalized lipodystrophy: glycemic and metabolic outcomes

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).

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.

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).

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.