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Aims <p>Sarcopenia, cachexia, and malnutrition are common in patients on immune checkpoint inhibitors (ICIs). GLP-1 receptor agonists (GLP-1 RAs) are increasingly used for weight management in patients with obesity, including those with cancer. Whether GLP-1 RA use at ICI initiation relates to wasting-related outcomes in patients without diabetes is unknown. We examined whether GLP-1 RA supply at ICI start was linked to wasting-related diagnoses and acute-care use.</p> Materials and methods <p>We used target-trial emulation with TriNetX US data. Adults with cancer and obesity/overweight starting an ICI were included. Baseline diabetes in the prior 12&#xa0;months were excluded, with a 90-day GLP-1 RA washout. Exposure was a GLP-1 RA prescription or administration within a prespecified 30-day peri-initiation window before or after ICI initiation, versus none. Cohorts were 1:1 propensity score matched and followed up to 36&#xa0;months; associations were estimated with intention-to-treat Cox models.</p> Results <p>After matching, 1974 patients were analyzed (987 per group). Over 36&#xa0;months, GLP-1 RA overlap was associated with fewer immune-related adverse events (HR 0.63, 95% CI 0.50–0.79); hospitalization (HR 0.67, 0.51–0.89), ICU (HR 0.69, 0.53–0.90), and emergency department visits (HR 0.68, 0.53–0.89) were also lower.</p> Conclusions <p>GLP-1 RA add-on at ICI initiation was associated with fewer recorded wasting-related diagnoses and less acute-care use. The all-cause mortality reduction is exploratory, likely reflecting channeling bias rather than causation. These findings support prospective evaluation of GLP-1 RAs as supportive-care add-on therapy in ICI-treated patients with obesity.</p>

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GLP-1 receptor agonists at immune checkpoint inhibitor initiation with immune-related and supportive-care outcomes in patients with cancer and overweight or obesity without diabetes: a target trial emulation

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月4日

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  • Yu-Jung Lin,
  • Pei-Yun Li,
  • Shao-Chia Chen,
  • Gideon Meyerowitz-Katz,
  • Yu-Nan Huang,
  • Pen-Hua Su

摘要

Aims

Sarcopenia, cachexia, and malnutrition are common in patients on immune checkpoint inhibitors (ICIs). GLP-1 receptor agonists (GLP-1 RAs) are increasingly used for weight management in patients with obesity, including those with cancer. Whether GLP-1 RA use at ICI initiation relates to wasting-related outcomes in patients without diabetes is unknown. We examined whether GLP-1 RA supply at ICI start was linked to wasting-related diagnoses and acute-care use.

Materials and methods

We used target-trial emulation with TriNetX US data. Adults with cancer and obesity/overweight starting an ICI were included. Baseline diabetes in the prior 12 months were excluded, with a 90-day GLP-1 RA washout. Exposure was a GLP-1 RA prescription or administration within a prespecified 30-day peri-initiation window before or after ICI initiation, versus none. Cohorts were 1:1 propensity score matched and followed up to 36 months; associations were estimated with intention-to-treat Cox models.

Results

After matching, 1974 patients were analyzed (987 per group). Over 36 months, GLP-1 RA overlap was associated with fewer immune-related adverse events (HR 0.63, 95% CI 0.50–0.79); hospitalization (HR 0.67, 0.51–0.89), ICU (HR 0.69, 0.53–0.90), and emergency department visits (HR 0.68, 0.53–0.89) were also lower.

Conclusions

GLP-1 RA add-on at ICI initiation was associated with fewer recorded wasting-related diagnoses and less acute-care use. The all-cause mortality reduction is exploratory, likely reflecting channeling bias rather than causation. These findings support prospective evaluation of GLP-1 RAs as supportive-care add-on therapy in ICI-treated patients with obesity.