Objective:

We examined the relationship between glucagon-like-peptide-1 (GLP-1) treatments and disease progression among amyotrophic lateral sclerosis (ALS) patients with diabetes mellitus (DM). 

Background:

GLP-1 agonists and dipeptidyl-peptidase-IV (DPP4) inhibitors increase GLP-1 activity resulting in delayed gastric emptying, decreased appetite, lower blood glucose levels, and weight loss. While these effects might have cardiovascular benefits, their impact on the progression of ALS remains unclear.

Design/Methods:

An IRB-approved electronic health record search was conducted to identify consecutive patients seen at a single institution from July/2020 to February/2024 with both ALS and DM diagnostic codes.  All charts were manually reviewed for demographics, anthropometric measures, disease history, medication use, and tracheostomy/survival.  Patients were excluded for not meeting Awaji ALS diagnostic criteria, lacking a documented history of DM, having insufficient records, or presenting to the first ALS clinic with a tracheostomy.  Patients were grouped by use of GLP-1 medications (GLP-1 agonists and DPP4 inhibitors). Tracheostomy-free survival was compared between the GLP-1 and no-GLP-1 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.

Results:

Among the 1,310 ALS patients screened, 85 had confirmed ALS and DM diagnosis, 36 (42%) of whom were treated with GLP-1 medicine(s). Sixty (71%) of the cohort died during follow-up.  Age at symptom onset, sex, race, bulbar onset frequency, riluzole use, and BMI were not significantly different between GLP-1 and no-GLP-1 groups. Tracheostomy-free survival from symptom onset was significantly shorter in the GLP-1 group (median survival 31 vs 45 months, p=0.004). After adjusting for covariates, the GLP-1 group was associated with increased mortality compared to the no-GLP-1 group (hazard ratio 3.3, 95% confidence interval [1.7, 6.2], p=0.0003).

Conclusions:

Treatment with GLP-1-related medications is associated with shorter survival in ALS patients with comorbid DM.