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

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Shneider doi: https://doi.org/10.1101/2025.05.05.25326993 Ikjae Lee 1 Eleanor and Lou Gehrig ALS Center, Department of Neurology, Columbia University Irving Medical Center , New York, NY 2 New York Presbyterian Hospital , New York, NY MD, MSc Find this author on Google Scholar Find this author on PubMed Search for this author on this site For correspondence: il2384{at}cumc.columbia.edu Jiyoon Hwang 1 Eleanor and Lou Gehrig ALS Center, Department of Neurology, Columbia University Irving Medical Center , New York, NY MPH Find this author on Google Scholar Find this author on PubMed Search for this author on this site Kathleen Stolwyk 2 New York Presbyterian Hospital , New York, NY MS, RD, CDN Find this author on Google Scholar Find this author on PubMed Search for this author on this site Matthew Harms 1 Eleanor and Lou Gehrig ALS Center, Department of Neurology, Columbia University Irving Medical Center , New York, NY 2 New York Presbyterian Hospital , New York, NY MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site Jinsy Andrews 1 Eleanor and Lou Gehrig ALS Center, Department of Neurology, Columbia University Irving Medical Center , New York, NY 2 New York Presbyterian Hospital , New York, NY MD, MSc Find this author on Google Scholar Find this author on PubMed Search for this author on this site Neil A. Shneider 1 Eleanor and Lou Gehrig ALS Center, Department of Neurology, Columbia University Irving Medical Center , New York, NY 2 New York Presbyterian Hospital , New York, NY MD, PhD Find this author on Google Scholar Find this author on PubMed Search for this author on this site Abstract Full Text Info/History Metrics Data/Code Preview PDF Abstract 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 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. Objective We examined the relationship between GLP-1RACT 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 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. Results Among 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). Conclusions Treatment with GLP-1RACT is associated with shorter tracheostomy-free survival in people with ALS and comorbid DM. Introduction Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive muscle weakness, leading to death in two to five years after symptom onset. 1 In the United States, approximately 5,000 new cases of ALS are diagnosed annually. 2 Despite the availability of various ALS treatments and ongoing research into new therapies, no cure currently exists to stop or reverse the progression of this disease. 3 Low adiposity and weight loss are common in ALS, and they are known risk factors for faster disease progression and shorter survival. 4 - 8 Current ALS treatment guidelines recommend stabilization of weight through gastrostomy and high-caloric supplements. 9 Recent observations also indicate that diets with higher glycemic index and load are associated with slower functional decline and longer survival, 10 , 11 suggesting the importance of adequate dietary glycemic responses. In this context, the recent rise of glucagon-like peptide-1 (GLP-1) receptor-activating medication use is concerning. 12 GLP-1 receptor agonists and dipeptidyl peptidase 4 (DPP4) inhibitors prolong the activation of GLP-1 receptors, leading to delayed gastric emptying, decreased blood glycemic responses, decreased appetite, and ultimately weight loss and reduced adiposity. 13 Although weight loss and low adiposity are associated with cardiovascular benefits in the general population, 14 it has been linked to rapid disease progression among the ALS population. 4 , 5 , 15 With the increasing use of GLP-1 agonists, it is likely that a growing number of ALS patients are being treated with these medications, raising concerns about their potential impact on ALS outcomes. In a recent case report, a person with ALS and type 2 DM progressed rapidly after the initiation of semaglutide, a commonly used GLP-1 receptor agonist. 16 It is currently unknown how frequently these GLP-1 receptor-activating medications are prescribed among people with ALS and whether they impact disease progression. In this single-center retrospective chart review study, we examined the relationship between GLP-1 receptor activator (GLP-1RACT) treatments and disease progression in people with ALS and comorbid DM. Specifically, we analyzed the frequency and patterns of antihyperglycemic medication use in this population and investigated differences in survival rates between those with and without GLP-1RACT treatments. Methods This was a retrospective chart review study. Institutional review board (IRB) approval to conduct chart reviews of the medical records was obtained (IRB# AAAV2579). Electronic health records were searched for ALS (ICD-10 G12.21) and DM (ICD-10 E08–E13) diagnostic codes or chart documentation between July 2020 and December 2024. Patients were included if they were over 18 years old, had a confirmed ALS diagnosis, met the Awaji ALS diagnostic criteria, 17 and had documented comorbid type 1 or type 2 DM. Those who did not meet these criteria or had undergone tracheostomy before their first clinic encounter were excluded. For patients who met inclusion and exclusion criteria, detailed chart reviews were conducted to extract data on demographics, anthropometric measures, disease history, functional assessments, medication use, tracheostomy status, and survival. Demographic variables included reported sex (male vs. female), race (White vs. Asian vs. Black vs. Other vs. Declined), and age at symptom onset. Anthropometric measures included height and weight at diagnosis. Body mass index (BMI) was calculated from height and weight. Disease history included the region of onset (spinal vs bulbar vs respiratory vs diffuse), diagnostic delay, first documented revised ALS functional rating scale (ALSFRS-r) total score, ALS medications (riluzole, edaravone, tofersen), and presence of pathogenic variants. Diagnostic delay was calculated as the difference, in days, between the date of ALS diagnosis and the date of symptom onset. If symptom onset was reported in month and year, 15 was imputed for the day. The rate of progression was calculated using the following formula: (48 – first measured ALSFRS-r)/disease duration from symptom onset to first ALSFRS-r measurement (months). Medications were reviewed, focusing on the DM medications. The name, first documented date, and last documented date of the DM medications were obtained. Survival and tracheostomy status with dates were recorded. If the patient survived beyond October 2024, the last known survival date was recorded. List of DM Medications Insulin: Insulin glulisine (Apidra®), Insulin aspart (Novolog®), Insulin lispro U-100/U-200 (Humalog®), Regular insulin (Novolin R, Humulin R), NPH insulin (Novolin N, Humulin N), Insulin detemir (Levemir®), Insulin U-100 (Lantus®, Basaglar®), Insulin glargine U-300 (Toujeo®), Insulin degludec U-100/U-200 (Tresiba®) Metformin (or containing metformin): ActoPlus Met®, ActoPlus Met XR®, Avandamet®, Fortamet®, Glucophage®, Glucophage XR®, Glucovance®, Glumetza®, Invokamet®, Janumet®, Janumet XR®, Jentadueto®, Kazano®, Kombiglyze XR®, Metaglip®, PrandiMet®, Riomet®, Xigduo XR GLP1 agonists: Dulaglutide (Trulicity®). Exenatide (Byetta®). Exenatide extended-release (Bydureon®). Liraglutide (Victoza®). Lixisenatide (Adlyxin®). Semaglutide injection (Ozempic®, Weagovy®). Semaglutide tablets (Rybelsus®), Terzepatide (Zepbound®). DPP4 inhibitors: sitagliptin (Januvia®, Zituvio®), sitagliptin+metformin (Janumet®), linagliptin (Tradjenta®), alogliptin (Nesina®, Vlpidia®), Saxagliptin (Onglyza®) Sodium-glucose cotransporter 2 (SGLT2) inhibitors: dapagliflozin(Farxiga®, Forxiga®), empagliflozin (Jardiance®), canagliflozin(Invokana®), ertugliflozin(Steglatro®) PPAR-r agonists: pioglitazone (Actos®), rosiglitazone (Avandia®) Sulfonylurea: glyburide(Glynase®), glimepiride(Amaryl®), glipizide (Glucotrol®) Meglitinide: repaglinide (Prandin®) Statistical Analysis Baseline characteristics were summarized and compared between ALS patients who received GLP-1RACT(GLP-1 receptor agonists or DPP4 inhibitors) and those without such exposures using T-tests for continuous variables and Chi-square tests for categorical variables. The Kaplan-Meier survival curves and log-rank tests were used to compare tracheostomy-free survival from symptom onset between participants with and without exposure to GLP-1RACT. Cox proportional hazard models were used to compare survival between groups, adjusted for covariates. Covariates included age, sex, bulbar onset, body mass index (BMI) at diagnosis, and riluzole intake. In sensitivity analysis, survivals were compared between groups based on individual classes of DM medications: GLP-1 receptor agonists; DPP4 inhibitors; biguanides; insulin; sulfonylurea; sodium-glucose cotransporter 2 (SGLT2) inhibitors; PPAR-r agonist; meglitinide. Statistical analyses were conducted using R version 4.4.1., a p-value less than 0.05 was considered significant. Results A total of 85 ALS patients were included in the analysis, with a mean age of 65 years and 65% male. The most commonly prescribed class of DM medication was biguanides (71%) followed by DPP4 inhibitors (33%), insulin (24.7%), SGLT2 inhibitor (18.8%), sulfonylurea (18.8%), GLP-1 receptor agonists (17.6%), PPAR-r agonists (5.9%), and meglitinide (1.1%). Among 85 patients, 36 patients (42%) took GLP-1RACT (either GLP-1 receptor agonists or DPP4 inhibitors or both), while 49 patients (58%) were never exposed (No-GLP-1RACT group). The mean age at diagnosis was 63.3 years in the GLP-1RACT group and 66.3 years in the No-GLP-1RACT group, with the difference not reaching statistical significance ( p = 0.2). GLP-1RACT group had a shorter diagnostic delay compared to the No-GLP-1RACT group (12.2 months vs . 18.4 months, p = 0.01). Onset region, BMI at diagnosis, first documented ALSFRS-r total score, rate of disease progression, and frequencies of riluzole and edaravone treatments were not significantly different between groups. [ Table 1 ] View this table: View inline View popup Download powerpoint Table 1. Baseline characteristics of ALS patients with and without the use of GLP-1RACT The Kaplan-Meier survival curve for tracheostomy-free survival demonstrates the separation of the curves between GLP-1RACT and No-GLP-1RACT groups (median survival 31 vs 45 months, p=0.0072). [ Figure 1 ] In Cox proportional hazard model adjusted for age, sex, bulbar onset, BMI at diagnosis, and riluzole intake, the GLP-1RACT group was associated with an increased risk of death (hazard ratio 3.1, 95% confidence interval (CI) [1.6, 6.0], p<0.001). Download figure Open in new tab Figure 1. Kaplan-Meier survival curve of ALS patients between GLP-1ACT (GLP-1 receptor agonists and DPP4 inhibitors) groups In sensitivity analysis, GLP-1 receptor agonist exposure was associated with shorter survival with a hazard ratio of 2.3 (95% CI [1.1, 4.9], p=0.03). DPP4 inhibitors exposure was also associated with shorter survival with a hazard ratio of 2.3 (95% CI [1.2, 4.5], p=0.01). Exposures to biguanide, insulin, sulfonylurea, SGLT2 inhibitors, PPAR-r agonists or meglitinide were not significantly associated with differences in tracheostomy-free survival. Discussions In this single-center retrospective chart review study, we investigated the associations between GLP-1 receptor-activating medication use and disease progression in people with ALS and DM. We observed that people treated with GLP-1 receptor agonists and/or DPP4 inhibitors had a significantly shorter diagnostic delay and tracheostomy-free survival compared to those who never received such medications. The hazard ratios for tracheostomy-free survival were similar between GLP-1 receptor agonists and DPP4 inhibitors when separately examined. After adjusting for other relevant prognostic factors, treatment with GLP-1 receptor-activating medication was associated with 3 times higher risk of death or tracheostomy. Exposures to other classes of DM medications were not significantly associated with tracheostomy-free survival. These findings suggest that the negative impact of GLP-1 receptor activators is not simply from the blood glucose lowering effect. Previous studies also reported that comorbid DM or blood hemoglobin A1C levels, a marker of average blood glucose levels, are not associated with survival in ALS. 18 , 19 What might be driving this negative impact of GLP-1 receptor-activating medications? GLP-1 is an incretin hormone that is secreted from the L-cells in the intestine, triggered by diet. 20 When bound to GLP-1 receptors in the brain, intestine, and pancreas, GLP-1 promotes the cellular uptake of glucose in the blood by increasing insulin and suppressing glucagon secretion. GLP-1 also provides negative feedback after eating by slowing gastric motility, promoting fullness, and suppressing appetite. After entering the bloodstream, GLP-1 gets quickly degraded by the DPP4 enzyme. GLP-1 receptor agonists are synthetic analogs of GLP-1 that are potent and resistant to degradation. DPP4 inhibitors prolong the effect of endogenous GLP-1 hormone by inhibiting degradation. Both GLP-1 agonists and DPP4 inhibitors moderate glycemic excursion and reduce peak glucose levels. 13 Blood glucose dynamics on these medications will be similar to that of lower glycemic index and load diet, 21 which was previously shown to be detrimental in ALS. 10 , 11 While the glucose dynamics are similarly affected, the weight loss effect of DPP4 inhibitors is not as prominent compared to GLP-1 receptor agonists. Based on our results that both GLP-1 receptor agonists and DPP4 inhibitors have similar degrees of negative impact on survival, we speculate that a change in glucose dynamics rather than weight loss might have played a major role in the disease progression. However, the current study does not provide data to test this hypothesis. Our study has limitations. First, as a retrospective analysis, it is subject to potential selection bias and unmeasured confounders. While we adjusted for key covariates, residual confounding cannot be ruled out. Second, the relatively small sample size and data deriving from a single center may limit the generalizability of our findings. Finally, while our study highlights an association between GLP-1 use and decreased survival, it does not establish causality. Future studies are urgently needed to confirm or refute our findings and further examine the underlying biological mechanisms driving this relationship, including the impact of GLP-1 therapy on metabolic homeostasis in people with ALS. Data Availability All data produced in the present study are available upon reasonable request to the authors Study funding The authors received no direct funding for this study. Conflict of interest disclosures IL received research funding from the National Institute of Health and Spastic Paraplegia Foundation, received consultation fees from Regeneron and Argenx pharmaceuticals. All other authors declare no conflict of interest exists. Footnotes Statistical analysis performed by: Ikjae Lee Search terms: 1. Amyotrophic Lateral Sclerosis 2. GLP-1 3. Survival 4. Progression 5. Diabetes Mellitus References 1. ↵ Rowland LP , Shneider NA . Amyotrophic lateral sclerosis . N Engl J Med . 2001 ; 344 ( 22 ): 1688 – 1700 . OpenUrl CrossRef PubMed Web of Science 2. ↵ Mehta P , Raymond J , Punjani R , et al. Incidence of amyotrophic lateral sclerosis in the United States, 2014–2016 . Amyotroph Lateral Scler Frontotemporal Degener . 2022 : 1 – 5 . 3. ↵ Oskarsson B , Gendron TF , Staff NP . Amyotrophic Lateral Sclerosis: An Update for 2018 . Mayo Clin Proc . 2018 ; 93 ( 11 ): 1617 – 1628 . OpenUrl CrossRef PubMed 4. ↵ Lee I , Kazamel M , McPherson T , et al. Fat mass loss correlates with faster disease progression in amyotrophic lateral sclerosis patients: Exploring the utility of dual-energy x-ray absorptiometry in a prospective study . PLoS One . 2021 ; 16 ( 5 ): e0251087 . OpenUrl CrossRef PubMed 5. ↵ Moglia C , Calvo A , Grassano M , et al. Early weight loss in amyotrophic lateral sclerosis: outcome relevance and clinical correlates in a population-based cohort . J Neurol Neurosurg Psychiatry . 2019 ; 90 ( 6 ): 666 – 673 . OpenUrl Abstract / FREE Full Text 6. Marin B , Desport JC , Kajeu P , et al. Alteration of nutritional status at diagnosis is a prognostic factor for survival of amyotrophic lateral sclerosis patients . J Neurol Neurosurg Psychiatry . 2011 ; 82 ( 6 ): 628 – 634 . OpenUrl Abstract / FREE Full Text 7. Tandan R , Levy EA , Howard DB , et al. Body composition in ALS subjects and its effect on disease progression and survival . Am J Clin Nutr . 2022 . 8. ↵ Wei QQ , Ou R , Cao B , et al. Early weight instability is associated with cognitive decline and poor survival in amyotrophic lateral sclerosis . Brain Res Bull . 2021 ; 171 : 10 – 15 . OpenUrl CrossRef PubMed 9. ↵ Miller RG , Jackson CE , Kasarskis EJ , et al. Practice parameter update: the care of the patient with amyotrophic lateral sclerosis: drug, nutritional, and respiratory therapies (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology . Neurology . 2009 ; 73 ( 15 ): 1218 – 1226 . OpenUrl CrossRef PubMed 10. ↵ Lee I , Mitsumoto H , Lee S , et al. Higher Glycemic Index and Glycemic Load Diet Is Associated with Slower Disease Progression in Amyotrophic Lateral Sclerosis . Ann Neurol . 2023 . 11. ↵ Lee I , Mitsumoto H , Lee S , et al. Interaction between riluzole treatment and dietary glycemic index in the disease progression of amyotrophic lateral sclerosis . Ann Clin Transl Neurol . 2025 . 12. ↵ Harris E. Poll: Roughly 12% of US Adults Have Used a GLP-1 Drug, Even If Unaffordable . JAMA . 2024 ; 332 ( 1 ): 8 . OpenUrl CrossRef 13. ↵ Gilbert MP , Pratley RE . GLP-1 Analogs and DPP-4 Inhibitors in Type 2 Diabetes Therapy: Review of Head-to-Head Clinical Trials . Front Endocrinol (Lausanne) . 2020 ; 11 : 178 . OpenUrl PubMed 14. ↵ Powell-Wiley TM , Poirier P , Burke LE , et al. Obesity and Cardiovascular Disease: A Scientific Statement From the American Heart Association . Circulation . 2021 ; 143 ( 21 ): e984 – e1010 . OpenUrl CrossRef PubMed 15. ↵ Tandan R , Levy EA , Howard DB , et al. Body composition in amyotrophic lateral sclerosis subjects and its effect on disease progression and survival . Am J Clin Nutr . 2022 ; 115 ( 5 ): 1378 – 1392 . OpenUrl PubMed 16. ↵ Stolwyk K , Lee I. Rapid progression of amyotrophic lateral sclerosis after initiation of GLP-1 agonist: a case report . Amyotroph Lateral Scler Frontotemporal Degener . 2025 : 1 – 3 . 17. ↵ Costa J , Swash M , de Carvalho M. Awaji criteria for the diagnosis of amyotrophic lateral sclerosis:a systematic review . Arch Neurol . 2012 ; 69 ( 11 ): 1410 – 1416 . OpenUrl CrossRef PubMed 18. ↵ Paganoni S , Hyman T , Shui A , et al. Pre-morbid type 2 diabetes mellitus is not a prognostic factor in amyotrophic lateral sclerosis . Muscle Nerve . 2015 ; 52 ( 3 ): 339 – 343 . OpenUrl PubMed 19. ↵ Lee I , Vestrucci M , Lee S , Rosenbaum M , Mitsumoto H. Blood glycated hemoglobin level is not associated with disease progression in amyotrophic lateral sclerosis . Amyotroph Lateral Scler Frontotemporal Degener . 2024 : 1 – 5 . 20. ↵ Orskov C. Glucagon-like peptide-1, a new hormone of the entero-insular axis . Diabetologia . 1992 ; 35 ( 8 ): 701 – 711 . OpenUrl PubMed Web of Science 21. ↵ Fabricatore AN , Ebbeling CB , Wadden TA , Ludwig DS . Continuous glucose monitoring to assess the ecologic validity of dietary glycemic index and glycemic load . Am J Clin Nutr . 2011 ; 94 ( 6 ): 1519 – 1524 . 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