Semaglutide Linked to Age-Related Macular Degeneration Risk

 

• Older diabetic patients on two GLP-1 drugs showed an increased risk of neovascular age-related macular degeneration in an observational cohort study.
• The absolute risk was small, however, reaching 0.2% at 3 years among GLP-1 medication users and 0.1% among non-users.
• Semaglutide represented the bulk of GLP-1 receptor agonists used in the study, hence the need for further investigation in this drug class.

Older adults taking GLP-1 receptor agonists, primarily semaglutide (Rybelsus, Ozempic, Wegovy), had a small uptick in their risk of developing neovascular age-related macular degeneration (nAMD), according to a retrospective, population-based cohort study from Canada.

Patients taking GLP-1 agonists for type 2 diabetes for at least 6 months had an excess risk of nAMD compared with matched non-users over 3 years of follow-up (adjusted HR 2.21, 95% CI 1.65-2.96), reported Reut Shor, MD, of the University of Toronto, and colleagues in JAMA Ophthalmologyopens in a new tab or window.

"The longer the exposure, the higher the risk seemed to be," Shor told MedPage Today. "This was definitely surprising, especially given the growing enthusiasm for GLP-1 receptor agonists for their cardiovascular and metabolic benefitsopens in a new tab or window."

While the absolute risks of nAMD were small in the study -- 0.2% versus 0.1% in non-users -- "it's important to remember that nAMD is a condition with profound implications for vision and quality of life," said Shor.

A growing literature nevertheless points to potential ocular safety concernsopens in a new tab or window with the GLP-1 receptor agonist drug class. Why there is a higher risk remains unknown, however.

While a rapid systemic reduction in glucose, including in the retina, may induce a temporary hypoxic state after use of GLP-1 agonists, the study authors reasoned that a prolonged increase in risk is more likely related to a mechanism of increased chemokine CXCL12 levels triggering vascular endothelial growth factor (VEGF) production.

"The adage that 'there is no such thing as a free lunch' remains true. While certainly not outweighing the good these medications offer, prescribing physicians need to keep in mind the real and serious ocular adverse events that may occur," according to Brian VanderBeek, MD, MPH, of the University of Pennsylvania Perelman School of Medicine in Philadelphia.

In an adjoining editorialopens in a new tab or window, he cited the early clinical trials that tied GLP-1 receptor agonists to diabetic retinal disease.

"This seemed counterintuitive, since nearly all other diabetic endpoints improved with these medications. Researchers then theorized that these results were not specific to GLP-1 RA [receptor agonist] use, but rather an effect of a disproportionate number of patients experiencing [diabetic retinal disease] paradoxical worsening after rapid blood glucose control -- an effect that was not expected to occur in the placebo group," VanderBeek wrote.

"Additional ocular concerns have been raised with recent reports of an increased occurrence of nonarteritic ischemic optic neuropathyopens in a new tab or window (NAION) associated with GLP-1 RA use,opens in a new tab or window" he added. "Again, the pathophysiologic mechanism is not clear, but it may be related to lower optic nerve head perfusion due to autonomic vascular dynamics and overall lower systemic blood pressure induced by GLP-1 RA use."

The editorialist stressed the need to assess whether other GLP-1 drugs can show a more favorable benefit-risk profileopens in a new tab or window, while the researchers cautioned the findings should not be generalized to specific brands -- in the study, semaglutide users accounted for 97.5% of the GLP-1 agonist use, the small remainder having used the discontinued lixisenatide (Adlyxin).

For their study, Shor and colleagues relied on data from Ontario's health system for 2020 to 2023. Individuals with diabetes ages 66 and older exposed to GLP-1 receptor agonists for 6 months or more were matched 1:2 to unexposed peers, resulting in a study cohort of 139,002 patients.

Altogether, the mean age was 66 years across the two groups, and 47% were women. The average duration of diabetes was just over 6 years, and 64% had hypertension.

According to the results, risk for nAMD was higher in those who had used the GLP-1 drugs for more than 30 months (adjusted HR 3.62, 95% CI 2.56-5.13) or 18 to 30 months (adjusted HR 2.26, 95% CI 1.49-3.45) versus those who had used them for 6 to 18 months (adjusted HR 0.94, 95% CI 0.53-1.65).

"Although not impossible, it seems unlikely that a person would progress from no AMD [age-related macular degeneration] to nAMD within 3 years. This would suggest there was an already at-risk group of patients with non-neovascular AMD within the cohort," commented VanderBeek.

"Future work should focus on controlling for the baseline level of AMD to determine if it is, in fact, this subgroup driving the results seen," he urged. "Next, work needs to be done to determine if this is an adverse effect only in patients with diabetes or if those using GLP-1 RAs for weight management or other indications are similarly at risk."

Shor's group acknowledged that the present study could not stratify risk by the different GLP-1 drugs and it did not account for factors such as dose, route of administration, and frequency of administration.

Disclosures

Shor reported research funding from the Silver Target Foundation. Co-authors reported relationships with the PSI Foundation, Fighting Blindness Canada, Alcon, Apellis, AbbVie, Bayer, Bausch, Roche, and the Silver Target Foundation.

VanderBeek reported consulting with EyePoint Pharmaceuticals and receipt of institutional research grants from Research to Prevent Blindness and the Paul and Evanina Mackall Foundation.

Primary Source

JAMA Ophthalmology

Source Reference: opens in a new tab or windowShor R, et al "Glucagon-like peptide-1 receptor agonists and risk of neovascular age-related macular degeneration" JAMA Ophthalmol 2025; DOI: 10.1001/jamaophthalmol.2025.1455.

Secondary Source

JAMA Ophthalmology

Source Reference: opens in a new tab or windowVanderBeek BL "Should we be concerned about glucagon-like peptide-1 receptor agonists?" JAMA Ophthalmol 2025; DOI: 10.1001/jamaophthalmol.2025.1599.

https://www.medpagetoday.com/ophthalmology/generalophthalmology/115919

Dollar Tree's tariff mitigation efforts will compensate for costs - J.P. Morgan

 Dollar Tree’s (NASDAQ:DLTR) warning of a $70M hit to Q2 cost of goods sold underscores that no matter how compelling the value proposition, no company is shielded from the costs and uncertainties tied to U.S. import tariffs.

The company beat on nearly all metrics with sales climbing 11.3%, traffic up 2.5%, average ticket increasing 2.8% and profits rising 2.4%, all pointing to the strength of the company’s operations and value to consumers.

However, shares were chased as much as 11% lower (before recovering losses on Thursday) as the forecasted cost of tariffs rattled investors.

“We're expecting a transitory impact on our near-term profitability as elevated costs run through our P&L in Q2, while the benefits and profit recovery from our mitigation efforts should materialize later in the year,” Dollar Tree CEO Michael Creedon told analysts on the company’s earnings call.

For J.P. Morgan’s Matthew Boss, tariff mitigation efforts will more than compensate for any near-term costs, and the company will return to double-digit EPS “compounder” with top- and bottom-line drivers in place at the Dollar Tree banner. Consequently, Boss upgraded Dollar Tree (NASDAQ:DLTR) to Overweight from Neutral with a 54% hike to his price target to $111.

“Taking a full year view, we believe that by successfully deploying our 5 levers, we will be able to mitigate most, if not all, of the potential earnings impact from higher tariffs, assuming the current levels remain in place,” Dollar Tree’s Creedon added on the call.

By employing this toolbox of “5 key levers” -- which includes negotiating with suppliers, adjusting product specification, moving country of origin, dropping “non-economic” items, and leveraging multi-price categories -- Boss thinks Dollar Tree (NASDAQ:DLTR) will not only mitigate the $70M COGS tariff headwind and end the year net-neutral with respect to tariffs, but enter the first half of 2026 with a wrap-around tailwind.

Despite Wednesday’s post-earnings hiccup, Dollar Tree (DLTR) continues to outperform its competitors with shares up 14% over the past month versus +11% for Amazon (AMZN), less than +1.0% for Costco (COST), and -1.3% for Walmart (WMT).

And analysts are largely bullish on the stock with Seeking Alpha authors and Wall Street analysts sharing a Buy rating. Seeking Alpha’s Quant rating views Dollar Tree with a more cautious Hold rating and Quant score of 3.17 out of 5.

https://www.msn.com/en-us/money/companies/dollar-tree-s-tariff-mitigation-efforts-will-compensate-for-costs-j-p-morgan/ar-AA1GapV1

Dem Rep. Balint: We Need Undocumented Immigrants To "Wipe Our A$$es"

 by Jonathan Turley,

There is a curious narrative emerging from Democratic politicians and pundits in support of the millions of undocumented persons who entered under the Biden Administration: they are perfect for menial tasks.

Rep. Jasmine Crockett (D., Texas) even argued that we need Hispanic immigrants to do things like pick our cotton. That seemed to echo the sentiments of Rep. Jerry Nadler (D. N.Y.), who warned that, without undocumented workers, we would not have anyone to pick our crops. Not to be outdone, Rep. Becca Balint (D., Vt.) opposed the efforts of the Trump Administration to close the border and deport unlawful immigrants because “we’re not going to have anyone around to wipe our a–es.” I wonder why Democrats are losing Hispanic voters.

Rep. Balint told Vermonters that  “we all know our ag system in Vermont would collapse without labor.” She maintained:

“If we don’t have avenues for people to come here legally to work or to build a home here, I’m going to be really crude right now, we’re not going to have anyone around to wipe our asses – because we don’t have enough people in our country now to fill the jobs that we have right now…”

Balint is not the only Vermont politician raising eyebrows this month.

Vermont has become ground zero for socialism with the rise of Sen. Bernie Sanders. 

State Rep. Teddy Waszazak, D-Barre, seemed ready for the central planners this month when he declared:

“Right now, our system is rigged against working people, our poorest neighbors, and the most vulnerable members of our communities. I feel very strongly about this — I feel the need to say this. The market picks winners and losers — it is the job of the government and tax code to right-size that.”

“Right sizing” the market has led to some of the most disastrous federal subsidies and programs in history.

It is really not the “market” picking winners and losers.

It is the aggregate of individual customers that is choosing products and services that they want.

On Sanders’ official website, a then-21-year-old Waszazak was shown professing how the American dream is dead, disputing the claim that “if you work hard, if you go to school, you will eventually be able to buy a house, have kids, and have whatever job you want to have… And I don’t think that’s true at all today.”

It is a crisis of faith in our system that is evident in calls to trash the Constitution, pack the Court, and counter the free market.

https://www.zerohedge.com/political/dem-rep-balint-we-need-undocumented-immigrants-wipe-our-aes

'Walz claims son knows why young men ditch Dems, turn to ‘incredibly dangerous’ Trump'

 Former vice presidential candidate Gov. Tim Walz shared an anecdote on Friday in which his son, Gus Walz, explained President Donald Trump’s unique appeal with young men.

Since the 2024 election, the Democratic Party has been reckoning with its lack of support from young men.

The New York Times recently published a report claiming that Democrats are spending $20 million on a study called, “Speaking with American Men: A Strategic Plan.”

The project aims to analyze “the syntax, language and content that gains attention and virality in these spaces” of male voters.

Walz shared some insight from his son, however, that came without such a price tag.

“[Gus] is pretty in tune to this, but what he said was, he said, ‘Dad, a lot of these young guys – they’re not voting on the policy issues,’” Tim Walz said during an interview on the “Grounded” podcast.

“And he wasn’t dissing them, he said they may know the policy issues, but most of them don’t. They’re doing it because there’s a sense of excitement, a sense of thrill in this, it’s entertainment or whatever.”

Walz highlighted how different this approach is from many experienced adults in the political world, noting, “We all dismiss that,” arguing many Trump critics say “‘Donald Trump’s a clown,’ you know, ‘Donald Trump’s rallies are a clown.’”

On the “Grounded” podcast, ex-vice presidential candidate Gov. Tim Walz said his son Gus revealed to him that young men are “not voting on the policy issues.”Grounded Podcast/Substack

Nonetheless, Walz argued the core of Trump’s appeal is telling young men, “You’ve got a place to belong.”

“I think — this is me just pontificating for what it’s worth,” he said.

“Social media and other things have disconnected people more than they were. We were more connected to my generation. It was easier to be a kid when I was growing up.”

Walz explained that the core of Trump’s appeal is telling young men, “You’ve got a place to belong.”AFP via Getty Images

He then warned that Trump taps into a deep need in American society.

“And I’ve always said this as a teacher: If you don’t give a kid a place to belong, they’ll go find one. So you want them to be involved in sports and music and things in school, because they will go find a group of folks,” he said. 

“And I think Donald Trump understands belonging, understands groups, I mean, look at it. He gives them a uniform, the red hat. He gives them some chants, some talking points, whatever. It’s not all that different than when we build sports teams in high school. ‘You belong, you are part of this,’” Walz added.

“It’s not so much the policies,” he said, echoing his son’s comment.

“I think it’s incredibly dangerous, but I don’t think we went out to get them. We didn’t go out to make them feel a part of this.”

https://nypost.com/2025/06/04/media/walz-recalls-how-son-explained-trumps-appeal-to-young-men-and-how-the-president-creates-a-sense-of-belonging/

Bogus social media accounts fueled backlash over Target rollback of DEI: ‘Manufactured outrage’

 A coordinated campaign used bogus social media accounts to amplify backlash against Target after the company scaled back its Diversity, Equity and Inclusion initiatives, according to a blockbuster report.

An analysis by Israeli tech firm Cyabra found that nearly a third of the social media accounts driving outrage over the retail giant’s policy change were fake.

The Minneapolis-based retailert announced it would roll back its controversial initiatives — which had drawn scorn from conservatives for touting items such as tuck-friendly bathing suits — after President Trump returned to the White House on Jan. 20.

Cyabra reviewed thousands of posts on Elon Musk-owned X, formerly Twitter, from Jan. 1 to April 21 and discovered that 27% of the accounts were inauthentic — many of which played a major role in pushing boycott narratives.

4

A coordinated disinformation campaign helped amplify backlash against Target, according to a report.REUTERS

Cyabra’s data showed that inauthentic posts jumped 764% after Target’s announcement, flooding the platform with calls for consumer boycotts and viral hashtags like #EconomicBlackout.

The firm’s CEO, Dan Brahmy, described the backlash as a calculated effort to manufacture outrage.

“What happened with Target is a masterclass in manufactured outrage,” Brahmy told The Post on Thursday.

“Fake accounts hijacked the narrative, weaponized identity and pushed a boycott that looked grassroots but was anything but. This is how influence operations work now — they blur the line between real and fake until no one can tell the difference.”

Many of the fake accounts were designed to mimic real users and took on the identities of black consumers or conservative commentators, according to Cyabra’s findings, which were obtained by The Post.

Some profiles pushed slogans such as “Target Fast” and “40-day boycott,” while others accused the retailer of “bending the knee” to Trump.

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Cyabra’s data showed that inauthentic posts jumped 764% after Target’s announcement that it was scaling back its DEI.Cyabra

One purported X user with the handle NenelsBack posted on Jan. 27: “@Target can’t get my money. It’s like being betrayed by a family member. We gave Target so much respect. BLK folk named Target, Targe’t.”

Another profanity-laced post on Jan. 24 said: “@Target You f—ing chicken sh-ts. You’re an embarrassment to Minnesota. Caving to Trump’s demands about DEI programs? F— you.”

A third simply fanned the flames for dissent.

“I stopped going to Target because of their support for the trans agenda. I think that is a greater motivation for people to boycott Target Target than DEI,” Nickolas Medina posted on the April 18.

All three were found to be posted by fake accounts, according to the report, first cited by USA Today.

“We don’t just look at what’s being said, we analyze how it’s being said, and whether they are even real,” Cyabra spokesperson Jill Burkes told The Post.

“We flag accounts that post in lockstep, recycle the same hashtags and slogans, or only interact within closed loops of other suspicious accounts.”

Cyabra, which uses artificial intelligence to detect coordinated manipulation campaigns, did not find clear evidence linking the campaign to a specific foreign or domestic actor.

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An Israeli analytics firm did a study which found a large number of posts from fake social media accounts fueled talk of a boycott.Cyabra

However, the tactic of inflaming culture war debates through synthetic engagement has become increasingly common, particularly in polarized consumer environments.

In a follow-up analysis of conversations on X from May 27 to June 3, Cyabra found the campaign had not only persisted but intensified. On some days, fake accounts made up 39% of the conversation –outnumbering genuine users.

Cyabra has seen similar tactics used against other major brands, from fast food chains to tech companies.

4

Cyabra reviewed thousands of posts on X, formerly Twitter, from Jan. 1 to April 21 and discovered that 27% of the accounts were inauthentic.Cyabra

“The playbook is similar: hijack a polarizing moment, flood the zone with fake voices and let real users do the rest,” Burkes said.

“That’s exactly what happened with Target. And it works — the stock dropped $12 billion and real people joined the boycott thinking they were part of a massive groundswell. Many still are.”

The Post has sought comment from Target.

Last month, Target lowered its full-year sales forecast. CEO Brian Cornell blamed several headwinds, including “the reaction to the updates we shared on [DEI] in January.”

Minneapolis activist Nekima Levy Armstrong, who launched a grassroots boycott of Target on Feb. 1, told USA Today she had no knowledge of the disinformation campaign identified by Cyabra.

“I’m not on X and I know our people in Minneapolis have no involvement in this situation,” Armstrong said.

https://nypost.com/2025/06/05/business/bogus-social-media-accounts-fueled-backlash-over-target-rollback-of-dei-report/