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Study · Observational study · 2025

6 results

Semaglutide and Nonarteritic Anterior Ischemic Optic Neuropathy.

Cai CX, Hribar M, Baxter S, Goetz K, Swaminathan SS, Flowers A, Brown EN, Toy B, Xu B, Chen J, Chen A, Wang S and 38 more

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Lee C, Leng T, Ehrlich JR, Barkmeier A, Armbrust KR, Boland MV, Dorr D, Boyce D, Alshammari T, Swerdel J, Suchard MA, Schuemie M, Bu F, Sena AG, Hripcsak G, Nishimura A, Nagy P, Falconer T, DuVall SL, Matheny M, Viernes B, O'Brien W, Zhang L, Martin B, Westlund E, Mathioudakis N, Fan R, Wilcox A, Lai A, Stocking JC, Takkouche S, Lee LH, Xie Y, Humes I, McCoy DB, Adibuzzaman M, Areaux RG Jr, Rojas-Carabali W

JAMA ophthalmology1 Apr 2025Cited by 88 (Europe PMC)

PMID39976940 (opens in a new tab)PMCIDPMC11843465 (opens in a new tab)DOI10.1001/jamaophthalmol.2024.6555 (opens in a new tab)PepBankPUB-39976940
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Summary

ImportanceSemaglutide, a glucagonlike peptide-1 receptor agonist (GLP-1RA), has recently been implicated in cases of nonarteritic anterior ischemic optic neuropathy (NAION), raising safety concerns in the treatment of type 2 diabetes (T2D).ObjectiveTo investigate the potential association between semaglutide and NAION in the Observational Health Data Sciences and Informatics (OHDSI) network.Design, setting, and participantsThis was a retrospective study across 14 databases (6 administrative claims and 8 electronic health records). Included were adults with T2D taking semaglutide, other GLP-1RA (dulaglutide, exenatide), or non-GLP-1RA medications (empagliflozin, sitagliptin, glipizide) from December 1, 2017, to December 31, 2023. The incidence proportion and rate of NAION were calculated. Association between semaglutide and NAION was assessed using 2 approaches: an active-comparator cohort design comparing new users of semaglutide with those taking other GLP-1RAs and non-GLP-1RA drugs, and a self-controlled case-series (SCCS) analysis to compare individuals' risks during exposure and nonexposure periods for each drug. The cohort design used propensity score-adjusted Cox proportional hazards models to estimate hazard ratios (HRs). The SCCS used conditional Poisson regression models to estimate incidence rate ratios (IRRs). Network-wide HR and IRR estimates were generated using a random-effects meta-analysis model.ExposuresGLP-1RA and non-GLP-1RAs.Main outcomes and measuresNAION under 2 alternative definitions based on diagnosis codes: one more inclusive and sensitive, the other more restrictive and specific.ResultsThe study included 37.1 million individuals with T2D, including 810 390 new semaglutide users. Of the 43 620 new users of semaglutide in the Optum's deidentified Clinformatics Data Mart Database, 24 473 (56%) were aged 50 to 69 years, and 26 699 (61%) were female. The incidence rate of NAION was 14.5 per 100 000 person-years among semaglutide users. The HR for NAION among new users of semaglutide was not different compared with that of the non-GLP-1RAs using the sensitive NAION definition-empagliflozin (HR, 1.44; 95% CI, 0.78-2.68; P = .12), sitagliptin (HR, 1.30; 95% CI, 0.56-3.01; P = .27), and glipizide (HR, 1.23; 95% CI, 0.66-2.28; P = .25). The risk was higher only compared with patients taking empagliflozin (HR, 2.27; 95% CI, 1.16-4.46; P = .02) using the specific definition. SCCS analysis of semaglutide exposure showed an increased risk of NAION (meta-analysis IRR, 1.32; 95% CI, 1.14-1.54; P < .001).Conclusions and relevanceResults of this study suggest a modest increase in the risk of NAION among individuals with T2D associated with semaglutide use, smaller than that previously reported, and warranting further investigation into the clinical implications of this association.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study6

6 results from studies that gave the peptide. 6 results from people.

  1. 01HumanObservational studySafety outcome

    In adults with type 2 diabetes, the incidence rate of NAION among semaglutide users was 14.5 per 100 000 person-years.

    In plain wordsIn adults with type 2 diabetes, about 14.5 per 100 000 person-years of semaglutide use had an optic nerve eye condition called NAION.

    Peptide
    Semaglutide
    Outcome
    Not applicableNAION incidence rate
    Study

    n: not reported in source

    Outcome group
    Adverse events · Eye
    Studied dose
    Dose not stated

    Measurements

    Incidence rate
    14.5 per 100 000 person-years
    semaglutide users

    Source sentences

    Summary
    The incidence rate of NAION was 14.5 per 100 000 person-years among semaglutide users.
    1 context sentence
    Summary · context
    Included were adults with T2D taking semaglutide, other GLP-1RA (dulaglutide, exenatide), or non-GLP-1RA medications (empagliflozin, sitagliptin, glipizide) from December 1, 2017, to December 31, 2023.
  2. 02HumanObservational studySafety outcome

    In adults with type 2 diabetes, NAION risk in new semaglutide users did not differ significantly from empagliflozin users using the sensitive definition.

    In plain wordsIn adults with type 2 diabetes, the eye condition NAION was not clearly more likely with semaglutide than with empagliflozin.

    Peptide
    Semaglutide
    Outcome
    No significant changeNAION hazard, semaglutide versus empagliflozin (sensitive definition)
    Study

    n: not reported in source

    Comparator
    Empagliflozin
    Outcome group
    Adverse events · Eye
    Studied dose
    Dose not stated

    Measurements

    Hazard ratio
    1.44 HR
    vs empagliflozin, sensitive definition

    Source sentences

    Summary
    The HR for NAION among new users of semaglutide was not different compared with that of the non-GLP-1RAs using the sensitive NAION definition-empagliflozin (HR, 1.44; 95% CI, 0.78-2.68; P = .12), sitagliptin (HR, 1.30; 95% CI, 0.56-3.01; P = .27), and glipizide (HR, 1.23; 95% CI, 0.66-2.28; P = .25).
    1 context sentence
    Summary · context
    Included were adults with T2D taking semaglutide, other GLP-1RA (dulaglutide, exenatide), or non-GLP-1RA medications (empagliflozin, sitagliptin, glipizide) from December 1, 2017, to December 31, 2023.
  3. 03HumanObservational studySafety outcome

    In adults with type 2 diabetes, NAION risk in new semaglutide users did not differ significantly from sitagliptin users using the sensitive definition.

    In plain wordsIn adults with type 2 diabetes, the eye condition NAION was not clearly more likely with semaglutide than with sitagliptin.

    Peptide
    Semaglutide
    Outcome
    No significant changeNAION hazard, semaglutide versus sitagliptin (sensitive definition)
    Study

    n: not reported in source

    Comparator
    Sitagliptin
    Outcome group
    Adverse events · Eye
    Studied dose
    Dose not stated

    Measurements

    Hazard ratio
    1.3 HR
    vs sitagliptin, sensitive definition

    Source sentences

    Summary
    The HR for NAION among new users of semaglutide was not different compared with that of the non-GLP-1RAs using the sensitive NAION definition-empagliflozin (HR, 1.44; 95% CI, 0.78-2.68; P = .12), sitagliptin (HR, 1.30; 95% CI, 0.56-3.01; P = .27), and glipizide (HR, 1.23; 95% CI, 0.66-2.28; P = .25).
    1 context sentence
    Summary · context
    Included were adults with T2D taking semaglutide, other GLP-1RA (dulaglutide, exenatide), or non-GLP-1RA medications (empagliflozin, sitagliptin, glipizide) from December 1, 2017, to December 31, 2023.
  4. 04HumanObservational studySafety outcome

    In adults with type 2 diabetes, NAION risk in new semaglutide users did not differ significantly from glipizide users using the sensitive definition.

    In plain wordsIn adults with type 2 diabetes, the eye condition NAION was not clearly more likely with semaglutide than with glipizide.

    Peptide
    Semaglutide
    Outcome
    No significant changeNAION hazard, semaglutide versus glipizide (sensitive definition)
    Study

    n: not reported in source

    Comparator
    Glipizide
    Outcome group
    Adverse events · Eye
    Studied dose
    Dose not stated

    Measurements

    Hazard ratio
    1.23 HR
    vs glipizide, sensitive definition

    Source sentences

    Summary
    The HR for NAION among new users of semaglutide was not different compared with that of the non-GLP-1RAs using the sensitive NAION definition-empagliflozin (HR, 1.44; 95% CI, 0.78-2.68; P = .12), sitagliptin (HR, 1.30; 95% CI, 0.56-3.01; P = .27), and glipizide (HR, 1.23; 95% CI, 0.66-2.28; P = .25).
    1 context sentence
    Summary · context
    Included were adults with T2D taking semaglutide, other GLP-1RA (dulaglutide, exenatide), or non-GLP-1RA medications (empagliflozin, sitagliptin, glipizide) from December 1, 2017, to December 31, 2023.
  5. 05HumanObservational studySafety outcome

    In adults with type 2 diabetes, NAION risk was higher with semaglutide than with empagliflozin using the specific definition.

    In plain wordsIn adults with type 2 diabetes, the eye condition NAION was more likely with semaglutide than with empagliflozin when a strict definition was used.

    Peptide
    Semaglutide
    Outcome
    IncreaseNAION hazard, semaglutide versus empagliflozin (specific definition)
    Study

    n: not reported in source

    Comparator
    Empagliflozin
    Outcome group
    Adverse events · Eye
    Studied dose
    Dose not stated

    Measurements

    Hazard ratio
    2.27 HR
    vs empagliflozin, specific definition

    Source sentences

    Summary
    The risk was higher only compared with patients taking empagliflozin (HR, 2.27; 95% CI, 1.16-4.46; P = .02) using the specific definition.
    1 context sentence
    Summary · context
    Included were adults with T2D taking semaglutide, other GLP-1RA (dulaglutide, exenatide), or non-GLP-1RA medications (empagliflozin, sitagliptin, glipizide) from December 1, 2017, to December 31, 2023.
  6. 06HumanObservational studySafety outcome

    In adults with type 2 diabetes, a self-controlled case series showed an increased NAION risk during semaglutide exposure compared with non-exposure periods.

    In plain wordsIn adults with type 2 diabetes, NAION was more likely during periods of semaglutide use than during periods without it.

    Peptide
    Semaglutide
    Outcome
    IncreaseNAION incidence rate ratio in self-controlled case series
    Study

    n: not reported in source

    Comparator
    Non-exposure periods
    Outcome group
    Adverse events · Eye
    Studied dose
    Dose not stated

    Measurements

    Incidence rate ratio
    1.32 IRR
    semaglutide exposure

    Source sentences

    Summary
    SCCS analysis of semaglutide exposure showed an increased risk of NAION (meta-analysis IRR, 1.32; 95% CI, 1.14-1.54; P < .001).
    1 context sentence
    Summary · context
    Included were adults with T2D taking semaglutide, other GLP-1RA (dulaglutide, exenatide), or non-GLP-1RA medications (empagliflozin, sitagliptin, glipizide) from December 1, 2017, to December 31, 2023.

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

  1. Versions 4 to 9Current

    28 Oct 2026, 02:03 UTC

    The same notice was added 6 times, first on 22 Oct 2026, 02:26 UTC. The status did not change between them.

    Study results updated

  2. Version 3

    21 Oct 2026, 18:59 UTC

    Study data updated · source update from Europe PMC

  3. Version 2

    11 Oct 2026, 00:04 UTC

    Study results updated

  4. Version 1

    9 Oct 2026, 03:06 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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