Efeitos da liraglutida, um agonista do receptor do peptídeo-1 semelhante ao glucagon (GLP-1), sobre parâmetros metabólicos e saciedade de pacientes com lipodistrofia generalizada congênita

Abstract

Lipodystrophies comprise rare, often underdiagnosed conditions characterized by partial or complete loss of subcutaneous adipose tissue, resulting in ectopic fat deposition in organs such as the pancreas, skeletal muscle, and liver, which may lead to severe metabolic complications. The spectrum of these complications is directly related to the extent of body fat loss, with generalized forms exhibiting more pronounced metabolic impairment and hyperphagia driven by markedly low leptin levels. The literature on the effects of glucagon-like peptide-1 receptor agonists in patients with lipodystrophies remains limited. Therefore, this study represents the first to evaluate the effects of liraglutide on metabolic parameters and satiety in patients with congenital generalized lipodystrophy (CGL). This open-label interventional study included patients with CGL followed by the Brazilian Group for the Study of Hereditary and Acquired Lipodystrophies (BRAZLIPO), who received liraglutide for 12 weeks. Metabolic outcomes

were assessed at baseline, after treatment (week 12), and following an additional 12-week off- treatment period (week 24), with complementary evaluation of body composition, satiety, and

hepatic imaging. Changes over time were analyzed using the Friedman test, with a significance level set at 5%. Eight patients were included (aged 24–45 years, six females); gastrointestinal adverse events led to treatment discontinuation in three patients. After 12 weeks of liraglutide therapy, a median reduction in HbA1c (−2.5%; range 1.1 to 3.1%; p=0.012) and in total daily insulin dose (−20%; range 0 to 100%; p=0.042) was observed, along with a non-significant reduction in triglycerides (−127 mg/dL; range 64 to 1171 mg/dL; p=0.350). Following treatment discontinuation, all patients exhibited increases in HbA1c and body weight of 2.2% (range 0.8 to 3.5%; p=0.026) and 3.6% (range 3.5 to 4.7%; p=0.001), respectively. Triglyceride levels increased in 80% of patients (median 421.5 mg/dL; range 76 to 1649; p=0.334). Insulin requirements also increased overall, with one patient resuming insulin at 0.4 U/kg/day and the others showing a median dose increase of 22% (range 12 to 50%; p=0.024). This study provides the first evidence that liraglutide may confer metabolic benefits in patients with CGL. Larger and longer-term studies are warranted to better characterize its effects on satiety, body composition, and liver disease in this population.