Cited by 38Amyotrophic Lateral Sclerosis ResearchLipoproteins and Cardiovascular HealthPharmaceutical Practices and Patient Outcomes

Antidiabetics, statins and the risk of amyotrophic lateral sclerosis

Open access
Mariosa, D., Kamel, F., Bellocco, R., Ronnevi, L.‐O., Almqvist, C., Larsson, H., Ye, W., Fang, F.·2020·European Journal of Neurology

Abstract

Background: Medications that are used for treatment of metabolic disorders have been suggested to be associated with the development of amyotrophic lateral sclerosis (ALS). Methods: To examine the associations of antidiabetics and statins with the subsequent risk of ALS we conducted a population‐based nested case‐control study of 2475 Swedish residents diagnosed with ALS during July 2006 to December 2013 and 12 375 population controls (five for each ALS case). We extracted information on filled prescriptions of antidiabetics and statins for both cases and controls from the Swedish Prescribed Drug Register during the years before ALS diagnosis. Conditional logistic regression was used to calculate odds ratios (ORs) for the associations of these medications with ALS risk. Results: Patients with ALS were less likely to have been prescribed with antidiabetics compared with controls [OR, 0.76; 95% confidence intervals (CI), 0.65–0.90]. Conversely, statins were not associated with ALS risk overall (OR, 1.08; 95% CI, 0.98–1.19), although a positive association was noted among women (OR, 1.28; 95% CI, 1.10–1.48). The latter association was mostly explained by ALS cases being more likely to have a first prescription of statins during the year before diagnosis compared with controls (OR, 2.54; 95% CI, 1.84–3.49). Conclusions: The inverse association of antidiabetics with ALS is consistent with the previously reported inverse association between type 2 diabetes and ALS risk. The increase in prescription of statins during the year before ALS diagnosis deserves attention because it might reflect an acceleration of the course of ALS due to statin use.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1111/ene.14190

Cites

4 of 4 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 22

  1. [1]Dupuis L, Corcia P, Fergani A, Dyslipidemia is a protective factor in amyotrophic lateral sclerosis. Neurology 2008; 70: 1004– 1009. 18199832
  2. [2]Sutedja NA, van der Schouw YT, Fischer K, Beneficial vascular risk profile is associated with amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry 2011; 82: 638– 642. 21471184
  3. [3]Mariosa D, Kamel F, Bellocco R, Ye W, Fang F. Association between diabetes and amyotrophic lateral sclerosis in Sweden. Eur J Neurol 2015; 22: 1436– 1442. 25600257 PMC4506907
  4. [5]Mariosa D, Hammar N, Malmstrom H, Blood biomarkers of carbohydrate, lipid, and apolipoprotein metabolisms and risk of amyotrophic lateral sclerosis: A more than 20-year follow-up of the Swedish AMORIS cohort. Ann Neurol 2017; 81: 718– 728. 28437840
  5. [6]Pradat PF, Bruneteau G, Gordon PH, Impaired glucose tolerance in patients with amyotrophic lateral sclerosis. Amyotroph Lateral Scler 2010; 11: 166– 171. 20184518
  6. [7]Ingre C, Chen L, Zhan Y, Lipids, apolipoproteins, and prognosis of amyotrophic lateral sclerosis. Neurology 2020. 10.1212/WNL.0000000000009322 PMC7274849 32221024 · DOI
  7. [8]Cardoso S, Correia S, Santos RX, Insulin is a two-edged knife on the brain. J Alzheimers Dis 2009; 18: 483– 507. 19542630
  8. [9]Sun H, Knippenberg S, Thau N, Therapeutic potential of N-acetyl-glucagon-like peptide-1 in primary motor neuron cultures derived from non-transgenic and SOD1-G93A ALS mice. Cell Mol Neurobiol 2013; 33: 347– 357. 23271639 PMC11498007
  9. [10]Dupuis L, Dengler R, Heneka MT, A randomized, double blind, placebo-controlled trial of pioglitazone in combination with riluzole in amyotrophic lateral sclerosis. PLoS One 2012; 7: e37885. 22715372 PMC3371007
  10. [11]Jawaid A, Paganoni S, Hauser C, Schulz PE. Trials of antidiabetic drugs in amyotrophic lateral sclerosis: proceed with caution? Neurodegener Dis 2014; 13: 205– 208. 24107404 PMC4435550
  11. [12]Kaneb HM, Sharp PS, Rahmani-Kondori N, Wells DJ. Metformin treatment has no beneficial effect in a dose-response survival study in the SOD1(G93A) mouse model of ALS and is harmful in female mice. PLoS One 2011; 6: e24189. 21909419 PMC3164704
  12. [13]Statins Beltowski J. and ALS: the possible role of impaired LXR signaling. Med Sci Monit 2010; 16: Ra73– 8. 20190699
  13. [14]Lee SH, Choi NY, Yu HJ, Atorvastatin protects NSC-34 motor neurons against oxidative stress by activating PI3K, ERK and free radical scavenging. Mol Neurobiol 2016; 53: 695– 705. 25577170
  14. [15]Golomb BA, Verden A, Messner AK, Koslik HJ, Hoffman KB. Amyotrophic lateral sclerosis associated with statin use: a disproportionality analysis of the FDA’s adverse event reporting system. Drug Safety 2018; 41: 403– 413. 29427042
  15. [16]Sorensen HT, Riis AH, Lash TL, Pedersen L. Statin use and risk of amyotrophic lateral sclerosis and other motor neuron disorders. Circ Cardiovasc Qual Outcomes 2010; 3: 413– 417. 20530788
  16. [18]Jawaid A, Salamone AR, Strutt AM, ALS disease onset may occur later in patients with pre-morbid diabetes mellitus. Eur J Neurol 2010; 17: 733– 739. 20074230
  17. [19]Ingre C, Roos PM, Piehl F, Kamel F, Fang F. Risk factors for amyotrophic lateral sclerosis. Clin Epidemiol 2015; 7: 181– 193. 25709501 PMC4334292
  18. [20]Longinetti E, Regodón Wallin A, Samuelsson K, The Swedish motor neuron disease quality registry. Amyotroph Lateral Scler Frontotemporal Degener 2018; 19: 528– 537. 30296856
  19. [21]Nefussy B, Hirsch J, Cudkowicz ME, Drory VE. Gender-based effect of statins on functional decline in amyotrophic lateral sclerosis. J Neurol Sci 2011; 300: 23– 27. 21056430
  20. [22]Su XW, Nandar W, Neely EB, Simmons Z, Connor JR. Statins accelerate disease progression and shorten survival in SOD1(G93A) mice. Muscle Nerve 2016; 54: 284– 291. 26799243 PMC5848093
  21. [23]Voora D, Shah SH, Spasojevic I, The SLCO1B1*5 genetic variant is associated with statin-induced side effects. J Am Coll Cardiol 2009; 54: 1609– 1619. 19833260 PMC3417133
  22. [26]Chipika RH, Finegan E, Li Hi Shing S, Hardiman O, Bede P. Tracking a fast-moving disease: longitudinal markers, monitoring, and clinical trial endpoints in ALS. Front Neurol 2019; 10: 229. 30941088 PMC6433752

Cited by

Sorted by citations

Authors
Mariosa, D., Kamel, F., Bellocco, R., Ronnevi, L. ‐., Almqvist, C., Larsson, H., Ye, W., & Fang, F.
Affiliations
  • Karolinska Institutet (SE)
  • National Institutes of Health (US)
  • Karolinska University Hospital (SE)
  • Örebro University (SE)
Corresponding author
Fang, F.
Venue
European Journal of Neurology
Publisher
Wiley
Published
2020-03-17
Volume
27
Issue
6
Pages
1010-1016
ISSN
  • 1351-5101 (ISSN-L)
  • 1468-1331
OpenAlex
W3008362605
Cited by
38
References
4
Citations by year
2026: 5 · 2025: 4 · 2024: 8 · 2023: 8 · 2022: 7 · 2021: 6
FWCI
2.27
Type
journal article
Language
en
Open access
Locations
  • European Journal of Neurology (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • INFM-OAR (INFN Catania) (submittedVersion, cc-by-nc)
  • BOA (University of Milano-Bicocca) (submittedVersion, cc-by-nc)
  • Zenodo (CERN European Organization for Nuclear Research) (cc-by)
Funders
  • EU Joint Programme – Neurodegenerative Disease Research
  • Forskningsrådet om Hälsa, Arbetsliv och Välfärd (2013‐00782)
  • Vetenskapsrådet (2019‐01088)
  • Karolinska Institutet
Topics
  • Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
  • Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
  • Health Sciences › Medicine › Geriatrics and Gerontology › Pharmaceutical Practices and Patient Outcomes
Keywords
amyotrophic lateral sclerosis, antidiabetic drugs, statins, medication use, ALS risk, type 2 diabetes, sex differences, ALS progression, prescribing patterns
MeSH terms
Amyotrophic Lateral Sclerosis, Diabetes Mellitus, Type 2, Female, Humans, Hypoglycemic Agents, Risk Factors, Sweden, Case-Control Studies, Hydroxymethylglutaryl-CoA Reductase Inhibitors

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review