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.

Abstract

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.