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Background <p>Cushing’s syndrome (CS) is characterized by profound metabolic derangements, including obesity, insulin resistance, diabetes mellitus, and dyslipidemia. Glucagon-like peptide-1 receptor agonists (GLP-1RA) have shown potent metabolic benefits in type 2 diabetes (T2D) and obesity, but their efficacy and safety in CS remain unexplored.</p> Objective <p>To assess the metabolic efficacy and safety of GLP-1RAs in patients with CS and concurrent T2D and/or obesity.</p> Methods <p>This retrospective multicenter study included 20 adults with biochemically confirmed CS treated with GLP-1RAs (liraglutide, semaglutide, tirzepatide, or dulaglutide) for ≥ 3 months. Anthropometric, hemodynamic, metabolic, hepatic, and hormonal parameters were compared before and after therapy using paired statistical tests.</p> Results <p>After a median follow-up of 13 months, significant reductions were observed in body weight (− 10.3 ± 8.8&#xa0;kg; <i>p</i> &lt; 0.001) and BMI (− 4.2 ± 2.8&#xa0;kg/m²; <i>p</i> &lt; 0.001). Fasting glucose (− 12.1 ± 35.3&#xa0;mg/dL; <i>p</i> = 0.015) and HbA1c (− 0.5 ± 0.9%; p = <i>0.011</i>) decreased significantly. No significant changes occurred in blood pressure or lipid parameters. Liver enzymes improved, with decreases in ALT (− 3.9 ± 21.4 U/L; <i>p</i> = 0.005) and GGT (− 25.9 ± 57.3 U/L; <i>p</i> = 0.012), while the slight reduction in AST (− 5.2 ± 9.2 U/L; <i>p</i> = 0.046) was statistically significant but not clinically relevant. Hormonal parameters, including ACTH and cortisol levels, remained stable. GLP-1RAs were generally well tolerated, with only mild gastrointestinal side effects in 26.3% of patients.</p> Conclusions <p>GLP-1RA therapy in patients with CS and associated metabolic disorders led to significant improvements in weight, BMI, and glycemic control without worsening cortisol dynamics or liver function. Although limited by its retrospective design and small sample size, this study supports the safety and potential metabolic efficacy of GLP-1RAs in patients with CS, suggesting that these agents may constitute a useful adjunct for managing obesity and diabetes in this population.</p>

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Efficacy and safety of GLP-1 receptor agonists in the treatment of type 2 diabetes and/or obesity in patients with Cushing’s syndrome: a multicenter retrospective study

  • 期刊论文

  • 发表日期：

    2026年3月10日

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  • Pedro Iglesias,
  • Ema L Nobre,
  • Felicia Hanzu,
  • Júnia R. O. L. Schweizer,
  • Lucía Manzano Valero,
  • Marta Araujo-Castro,
  • Ana Castro Luna,
  • Francisco Javier Albacete,
  • Rocío Villar-Taibo,
  • Martin Reinke

摘要

Background

Cushing’s syndrome (CS) is characterized by profound metabolic derangements, including obesity, insulin resistance, diabetes mellitus, and dyslipidemia. Glucagon-like peptide-1 receptor agonists (GLP-1RA) have shown potent metabolic benefits in type 2 diabetes (T2D) and obesity, but their efficacy and safety in CS remain unexplored.

Objective

To assess the metabolic efficacy and safety of GLP-1RAs in patients with CS and concurrent T2D and/or obesity.

Methods

This retrospective multicenter study included 20 adults with biochemically confirmed CS treated with GLP-1RAs (liraglutide, semaglutide, tirzepatide, or dulaglutide) for ≥ 3 months. Anthropometric, hemodynamic, metabolic, hepatic, and hormonal parameters were compared before and after therapy using paired statistical tests.

Results

After a median follow-up of 13 months, significant reductions were observed in body weight (− 10.3 ± 8.8 kg; p < 0.001) and BMI (− 4.2 ± 2.8 kg/m²; p < 0.001). Fasting glucose (− 12.1 ± 35.3 mg/dL; p = 0.015) and HbA1c (− 0.5 ± 0.9%; p = 0.011) decreased significantly. No significant changes occurred in blood pressure or lipid parameters. Liver enzymes improved, with decreases in ALT (− 3.9 ± 21.4 U/L; p = 0.005) and GGT (− 25.9 ± 57.3 U/L; p = 0.012), while the slight reduction in AST (− 5.2 ± 9.2 U/L; p = 0.046) was statistically significant but not clinically relevant. Hormonal parameters, including ACTH and cortisol levels, remained stable. GLP-1RAs were generally well tolerated, with only mild gastrointestinal side effects in 26.3% of patients.

Conclusions

GLP-1RA therapy in patients with CS and associated metabolic disorders led to significant improvements in weight, BMI, and glycemic control without worsening cortisol dynamics or liver function. Although limited by its retrospective design and small sample size, this study supports the safety and potential metabolic efficacy of GLP-1RAs in patients with CS, suggesting that these agents may constitute a useful adjunct for managing obesity and diabetes in this population.