GLP-1 receptor agonist use is associated with shorter survival in patients with amyotrophic lateral sclerosis and diabetes mellitus

Background: The glucagon-like-peptide-1 (GLP-1) hormone exerts metabolic effects leading to delayed gastric emptying, decreased appetite, and lower blood glucose levels. GLP-1 receptor agonists (GLP-1RA) are increasingly used to treat diabetes mellitus (DM) and obesity. However, their impact on the progression of amyotrophic lateral sclerosis (ALS) is unknown. Objective: We examined the relationship between GLP-1RA treatment and disease progression among people with ALS and DM. Methods: An electronic health record search was conducted to identify consecutive patients seen at a single institution from 2020 to 2024 with ALS and DM diagnostic codes. All charts were reviewed for demographics, disease history, medication use, and tracheostomy/survival. Patients who did not meet Awaji ALS diagnostic criteria, lacked a documented history of DM, or had insufficient records were excluded. Patients were grouped by GLP-1RA exposure. Tracheostomy-free survival was compared between the GLP-1RA and No-GLP-1RA groups using Kaplan-Meier survival curves, log-rank test and Cox-proportional hazard models adjusted for age, sex, bulbar onset, body mass index (BMI) at diagnosis, and riluzole use. Results: Total 1,310 ALS patients were screened, 136 patients (10%) had comorbid DM. After chart review, 85 patients meeting inclusion and exclusion criteria were included, 15 (18%) of whom were treated with GLP-1RA. Compared to No-GLP-1RA group, GLP-1RA group was younger at symptom onset (59 vs 66 years old, p<0.01), had shorter diagnostic delay (12 months vs 17 months, p=0.04) and higher weight at diagnosis (85kg vs 73kg, p=0.02). Tracheostomy-free survival from symptom onset trended shorter in the GLP-1RA group (median survival 28.7 vs 34.9 months, p=0.08). After adjusting for covariates, the GLP-1RA group was associated with increased mortality compared to the No-GLP-1RA group (hazard ratio 2.5, 95% confidence interval [1.1, 5.3], p=0.02). Conclusions: Treatment with GLP-1RA is associated with shorter tracheostomy-free survival in people with ALS and comorbid DM.