GLP-1-related antihyperglycemic medication use is associated with shorter survival in patients with amyotrophic lateral sclerosis and diabetes mellitus

BackgroundThe 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 activators (GLP-1RACT) are increasingly used to treat diabetes mellitus (DM) and obesity. However, their impact on the progression of amyotrophic lateral sclerosis (ALS) is unknown. ObjectiveWe examined the relationship between GLP-1RACT treatment and disease progression among people with ALS and DM. MethodsAn electronic health record search was conducted to identify consecutive patients seen at a single institution from July/2020 to February/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. Those who were treated with GLP-1 receptor agonists or dipeptidyl peptidase-4 inhibitors were grouped with GLP-1RACT. The others were grouped with No-GLP-1RACT. Tracheostomy-free survival was compared between the GLP-1RACT and No-GLP-1RACT groups using Kaplan-Meier survival curves and Cox-proportional hazard models adjusted for age, sex, bulbar onset, body mass index (BMI) at diagnosis, and riluzole use. ResultsAmong the 1,310 ALS patients screened, 85 had confirmed ALS and DM diagnosis, 36 (42%) of whom were treated with GLP-1RACT. Sixty (71%) of the cohort died during follow-up. Diagnostic delay was shorter in GLP-1RACT compared to the No-GLP-1RACT group (371 vs 561 days, p=0.01). Other baseline characteristics were not significantly different between groups. Tracheostomy-free survival from symptom onset was significantly shorter in the GLP-1RACT group (median survival 31 vs 45 months, p=0.007). After adjusting for covariates, the GLP-1RACT group was associated with increased mortality compared to the No-GLP-1RACT group (hazard ratio 3.1, 95% confidence interval [1.6, 6.0], p<0.001). ConclusionsTreatment with GLP-1RACT is associated with shorter tracheostomy-free survival in people with ALS and comorbid DM.