A claim you hear on longevity podcasts

Is the risk of NAION from Ozempic very small?

The claim checked: The eye-stroke risk on GLP-1 drugs is very small, and they do not raise pancreatitis or bowel blockage Hear it at 41:04

What do the studies say?

Strong consensus for

Seven studies found the risk of NAION, a stroke of the optic nerve, was low in absolute terms or not raised on semaglutide. A pooled analysis of trials put it at 1 more case per 10 000 people. One clinic study found 8.9% against 1.8% over 36 months. Two found a raised relative risk with no absolute figure.

Computed from 10 studies that test this point, each judged by two readers, in full.

The study behind the claim tested something else. See what it tested

What was said on the podcast?

“study just came out July 2026 JAMA Ophthalmology basically showing that it's an increase of about 300th of 1 percentage point. It's very, very low.”
Tyna Moore, a guest on The Dr. Hyman Show · What We Got Wrong About GLP-1s (And What's Actually Right) · 41:04 on YouTube
The study behind the claim The retelling overstates it

What did the study actually test?

On tape: a July 2026 JAMA Ophthalmology study. The matching study ran in Annals of Internal Medicine in July 2026. Its risk difference was 3.0 per 10,000 (0.03 percentage points), larger than the 300th of a percentage point said on tape; the authors also call the absolute risk very low. Glucagon-like Peptide-1 Receptor Agonists and Risk for Ischemic Optic Neuropathy : A Target Trial Emulation. Ann Intern Med, 2026. Target trial emulation in a US commercial claims database, 2017 to 2022, Adults aged 18 to 65 with type 2 diabetes starting a GLP-1 drug, an SGLT2 inhibitor or a DPP4 inhibitor.

What was saidWhat the study did
What was given Matches GLP-1 drugs Starting a GLP-1 receptor agonist
Compared with Differs People not taking them People starting an SGLT2 or DPP4 inhibitor
What was measured Matches NAION, an eye stroke Ischemic optic neuropathy, as a proxy for NAION, over 18 months
Who took part Differs Mostly people living with diabetes Adults aged 18 to 65 with type 2 diabetes

What it found

“The 18-month risk for ION was 8.5 versus 5.5 per 10 000 among GLP-1RA users versus SGLT2i users (RD, 3.0 [95% CI, 0.4 to 5.7]) and 7.8 versus 4.2 per 10 000 among GLP-1RA users versus DPP4i users (RD, 3.6 [CI, 1.1 to 6.1]).”

PMID 42441967

How the authors extend it

“Use of GLP-1RAs was associated with higher 18-month risk for ION than use of SGLT2is and DPP4is, although absolute risk remained very low.”

PMID 42441967

PRIMARY FUNDING SOURCE: National Institutes of Health. Two readers agreed on the label.

Point 1 of 2 Strong consensus for

The absolute rise in NAION (an optic nerve stroke) on semaglutide or other GLP-1 drugs is very small

Agree 7

trial or observed group · 2025 · landmark

“In conclusion, in this retrospective study, we identified a small increased risk of NAION among patients with T2D who were exposed to semaglutide, smaller than that previously reported.”

Semaglutide and Nonarteritic Anterior Ischemic Optic Neuropathy. JAMA Ophthalmol
Who: Adults 18 years and older with type 2 diabetes in 14 OHDSI claims and EHR databases (US and others) who were new users of semaglutide, dulaglutide, exenatide, empagliflozin, sitagliptin or glipizide, December 2017-December 2023
PMID 39976940

trial or observed group · 2025 · landmark

“Our large, multinational, population-based study found that semaglutide is not associated with an increased risk of NAION in the general population.”

Association between Semaglutide and Nonarteritic Anterior Ischemic Optic Neuropathy: A Multinational Population-Based Study. Ophthalmology
Who: White adults aged 18 or older with type 2 diabetes and/or obesity in the TriNetX network (160 health care organizations, 21 countries), split into T2DM-only, obesity-only and T2DM-with-obesity cohorts, semaglutide vs non-GLP-1 RA glucose-lowering or weight-loss drugs
PMID 39491755

other primary study · 2024 · landmark

“As such, the observed incidence rate of NAION of 0·228 per 1000 person-years for persons with T2D exposed with once-weekly semaglutide may not discourage semaglutide treatment but needs to be acknowledged as a potential risk.”

Once-weekly semaglutide doubles the five-year risk of nonarteritic anterior ischemic optic neuropathy in a Danish cohort of 424,152 persons with type 2 diabetes. Int J Retina Vitreous
Who: All adults with type 2 diabetes in Denmark 2018-2024 from national registers, 106,454 exposed to once-weekly semaglutide (Ozempic) vs 317,698 unexposed; median age 65
PMID 39696569

Show 4 more Show fewer

other primary study · 2025 · landmark

“In conclusion, our findings support an association between the use of semaglutide for type 2 diabetes and the risk of NAION, with a more than two‐fold increased HR compared with the use of SGLT‐2is. However, the absolute risk of NAION remains low among semaglutide users.”

Use of semaglutide and risk of non-arteritic anterior ischemic optic neuropathy: A Danish-Norwegian cohort study. Diabetes Obes Metab
Who: New users of semaglutide or SGLT-2 inhibitors for type 2 diabetes in Danish and Norwegian nationwide registries, 2018-2024 (Denmark) / 2018-2022 (Norway); plus a self-controlled analysis of all semaglutide initiators regardless of indication
PMID 40098249

other primary study · 2025 · landmark

“This study demonstrates no significant difference in the risk of NAION or ION in diabetic or overweight/obese patients prescribed semaglutide compared to matched controls on non-GLP-1RA medications at multiple time points.”

The Effect of Semaglutide and GLP-1 RAs on Risk of Nonarteritic Anterior Ischemic Optic Neuropathy. Am J Ophthalmol
Who: US patients in the TriNetX network (65 institutions) seen by ophthalmology or neurology services, with type 2 diabetes or BMI 25 or higher, prescribed semaglutide or any GLP-1RA vs propensity-matched non-GLP-1RA users
PMID 40015592

other primary study · 2025 · landmark

“The risk of NAION was modestly higher among the treatment group than the control group (96 [0.1%] vs 79 [<0.1%] events; HR, 1.26 [95% CI, 0.94-1.70]; P = .12), as was the risk of a broader set of ischemic optic nerve conditions (243 [0.1%] vs 230 [0.1%] events; HR, 1.10 [95% CI, 0.92-1.32]; P = .31).”

GLP-1 Receptor Agonists and Sight-Threatening Ophthalmic Complications in Patients With Type 2 Diabetes. JAMA Netw Open
Who: US TriNetX adults with type 2 diabetes and HbA1c 6.5% or higher, 185,066 with at least 2 GLP-1 RA prescriptions 6 months apart (semaglutide, lixisenatide, tirzepatide, dulaglutide, liraglutide or exenatide) propensity-matched to 185,066 without; mean age 59
PMID 40788647

pooled analysis · 2025 · landmark

“GRADEpro showed an absolute effect of 1 more per 10 000 study participants (95% CI, from 0 fewer to 4 more), with a low certainty of evidence (eTable 6 in Supplement 1).”

Ocular Adverse Events With Semaglutide: A Systematic Review and Meta-Analysis. JAMA Ophthalmol
Who: Adults in randomized trials of oral or subcutaneous semaglutide vs placebo or active comparator (52 trials in diabetes, 13 in overweight/obesity without diabetes, 4 in NAFLD); mean age 33-70
PMID 40810985

Partly agree 2

other primary study · 2025 · landmark

“Across the entire study duration, there was an increased risk for NAION associated with semaglutide use among patients with diabetes compared with non–GLP-1 RA users (HR, 2.22; 95% CI, 1.37-3.60).”

Semaglutide and Nonarteritic Anterior Ischemic Optic Neuropathy Risk Among Patients With Diabetes. JAMA Ophthalmol
Who: US TriNetX patients aged 12 or older with diabetes, 174,584 prescribed semaglutide propensity-matched 1:1 with 174,584 prescribed non-GLP-1 RA antidiabetic drugs; mean age about 58
PMID 40146102

trial or observed group · 2025 · landmark

“In light of the substantial benefits provided by GLP-1 RAs, including improved glycemic control, cardiovascular risk reduction, and effective weight management, the absolute risk of NAION with semaglutide appears to be low.”

Association of Glucagon-Like Peptide-1 Receptor Agonists With Optic Nerve and Retinal Adverse Events: A Population-Based Observational Study Across 180 Countries. Am J Ophthalmol
Who: Spontaneous adverse-event reports in US FAERS (12,936,341 reports) and WHO VigiBase (over 35 million reports, 180+ countries) for semaglutide and tirzepatide vs all other drugs or metformin, empagliflozin, dulaglutide, insulin
PMID 40383360

Disagree 1

other primary study · 2024 · landmark

“The Kaplan-Meier survival analysis at 36 months showed a cumulative incidence of NAION of 8.9% (95% CI, 4.5%-13.1%) for the semaglutide cohort vs 1.8% (95% CI, 0%-3.5%) for the nonsemaglutide cohort.”

Risk of Nonarteritic Anterior Ischemic Optic Neuropathy in Patients Prescribed Semaglutide. JAMA Ophthalmol
Who: 16,827 patients seen in a single academic neuro-ophthalmology service (Massachusetts Eye and Ear, 2017-2023); analysed cohorts of 710 with type 2 diabetes (194 semaglutide vs 516 non-GLP-1 RA) and 979 overweight or obese (361 semaglutide vs 618 non-GLP-1 RA)
PMID 38958939

Point 2 of 2 Leaning for

GLP-1 drugs do not significantly raise the risk of pancreatitis, bowel obstruction or gallbladder inflammation

Two studies found no rise in pancreatitis, a swollen pancreas, or in gallbladder disease. More pancreatitis or digestive disease showed up in two others. Six found more gallbladder problems, mostly gallstones, or a mixed picture.

Computed from 10 studies that test this point, each judged by two readers, in full. 3 more studies are waiting for a full read and do not count yet.

Agree 2

other primary study · 2025

“In adjusted, per protocol, main analyses, no risk differences were found for acute pancreatitis (hazard ratio [HR]: 0.56; 95% confidence interval [95CI%]: 0.17-1.91) nor for biliary disease (HR: 1.12; 95%IC: 0.79-1.58) (Table 2).”

Association of glucagon-like peptide-1 receptor agonists with acute pancreatitis and biliary disease in individuals with diabetes and obesity: a propensity-weighted, population-based cohort study. Gac Sanit
Who: Adults with diabetes and obesity (BMI 30 or more) on metformin in the Valencia region of Spain who newly started a GLP-1 RA or an SGLT-2 inhibitor, 2015-2021
PMID 39818039

other primary study · 2026

“No supporting evidence could verify the association of GLP1R expression with the other gastrointestinal diseases.”

Genetic evidence for a causal protective effect of GLP-1 receptor agonists on paralytic ileus but not on other gastrointestinal events. Medicine (Baltimore)
Who: European-ancestry individuals in eQTLGen and IEU GWAS (mostly UK Biobank) summary data; validation in 407 704 UK Biobank participants aged 40-69
PMID 41861181

Partly agree 6

pooled analysis · 2025

“While these events were more frequent with tirzepatide treatment, semaglutide was significantly associated with gallbladder disease and cholelithiasis, regardless of gender. No statistically significant incidence of pancreatitis or hepatic events were observed with either treatment compared to the control.”

Gastrointestinal safety of semaglutide and tirzepatide vs. placebo in obese individuals without diabetes: a systematic review and meta analysis. Ann Saudi Med
Who: Adults with obesity (BMI 30 or higher, or 27 or higher with comorbidity) without diabetes in randomized controlled trials of semaglutide or tirzepatide vs control
PMID 40189856

other primary study · 2026

“In conclusion, genetic variants associated with GLP-1RA target genes (GLP1R/CNR1) show associations with acute pancreatitis risk in MR analyses.”

Association of glucagon-like peptide-1 receptor agonists with risk of gastrointestinal adverse events: evidence from a drug target Mendelian randomization. Eur Heart J Cardiovasc Pharmacother
Who: European-ancestry GWAS and eQTL summary data (eQTLGen, GTEx V8, UK Biobank, FinnGen)
PMID 40874865

controlled trial · 2016 · landmark

“There were more episodes of gallstone disease with liraglutide, a finding that has been reported previously.”

Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med
Who: Adults with type 2 diabetes (HbA1c 7.0% or more), aged 50 or older with cardiovascular disease or 60 or older with cardiovascular risk factors, randomized to liraglutide or placebo (LEADER trial)
PMID 27295427

Show 3 more Show fewer

controlled trial · 2021 · landmark

“Gallbladder-related disorders (mostly cholelithiasis) were reported in 2.6% and 1.2% of participants in the semaglutide and placebo groups, respectively.”

Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med
Who: Adults without diabetes with BMI 30 or more (or 27 or more with a weight-related condition), 129 sites in 16 countries; mean age 46, 74.1% female
PMID 33567185

controlled trial · 2022 · landmark

“Cholecystitis and acute cholecystitis were reported more frequently in the tirzepatide groups than in the placebo group, although the incidences were low (≤0.6%) (Table 4).”

Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med
Who: Adults without diabetes with BMI 30 or more (or 27 or more with a weight-related complication) at 119 sites in nine countries; mean weight 104.8 kg, mean BMI 38.0
PMID 35658024

controlled trial · 2023 · landmark

“The incidence of gallbladder-related disorders was higher with semaglutide than with placebo, an association that has also been reported previously.”

Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes. N Engl J Med
Who: 17,604 patients aged 45 years or older with preexisting cardiovascular disease and BMI of 27 or greater but no history of diabetes
PMID 37952131

Disagree 2

pooled analysis · 2022

“In general, neither SGLT2is nor DPP4is are associated with the occurrences of various kinds of digestive diseases, whereas GLP1RAs are associated with the higher risks of 4 kinds of digestive diseases, namely, gastric ulcer hemorrhage, pancreatitis, cholangitis acute, and cholecystitis acute.”

Meta-analysis of the association between new hypoglycemic agents and digestive diseases. Medicine (Baltimore)
Who: Participants in large placebo-controlled cardiorenal outcome trials of SGLT2is, GLP1RAs or DPP4is (at least 1000 per arm), mainly adults with type 2 diabetes at high cardiorenal risk
PMID 36042668

other primary study · 2013 · landmark

“Our findings suggest a significantly increased risk of hospitalization for acute pancreatitis associated with the use of sitagliptin or exenatide among adult patients with type 2 diabetes mellitus.”

Glucagonlike peptide 1-based therapies and risk of hospitalization for acute pancreatitis in type 2 diabetes mellitus: a population-based matched case-control study. JAMA Intern Med
Who: US adults aged 18 to 64 years with type 2 diabetes in 7 Blue Cross Blue Shield plans; 1269 hospitalized acute pancreatitis cases and 1269 matched controls
PMID 23440284

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