Study Compares GLP-1 Drugs on Their Benefits, Harms

 Variable weight-loss and cardiovascular benefits were seen with GLP-1 drugs in a systematic review and network meta-analysis, but effects on quality of life were less clear.

Across 262 randomized studies published through November 2025, moderate- to high-certainty evidence showed weight loss with the following GLP-1 drugs at 1 year versus lifestyle modification alone:

• Tirzepatide (Zepbound): mean difference -14.9% (95% CI -16.0 to -13.9)
• Cagrilintide-semaglutide (CagriSema): mean difference -14.8% (95% CI -16.9 to -12.7)
• Oral semaglutide (Rybelsus): mean difference -10.9% (95% CI -12.7 to -9.1)
• Orforglipron (Foundayo): mean difference -9.9% (95% CI -12.4 to -7.5)
• Subcutaneous semaglutide (Wegovy): mean difference -9.8% (95% CI -10.6 to -9.1)

Subcutaneous semaglutide (risk ratio [RR] 0.43, 95% CI 0.21-0.84) and tirzepatide (RR 0.49, 95% CI 0.27-0.88) were also both associated with reduced heart failure risk, while subcutaneous semaglutide stood alone in being tied to a reduced risk of all-cause mortality (RR 0.81, 95% CI 0.72-0.93) and myocardial infarction (RR 0.72, 95% CI 0.61-0.85), reported Sheyu Li, MD, of West China Hospital and Sichuan University in Chengdu, China, and colleagues.

Less certain was the evidence that these drugs could reduce kidney failure or improve quality of life beyond a subjective threshold, they noted in The BMJ.

"Obesity drugs produce variable weight loss at 1 year, with larger benefits generally accompanied by greater harms and discontinuation," the authors wrote. "Most agents do not improve quality of life meaningfully and few show cardiovascular benefits. Decisions in clinical practice should consider trade-offs between benefits and harms within the context of shared decision making."

However, on the U.K. Science Media Centre website, experts urged careful consideration of what the data actually show.

Hamid Merchant, PhD, MPharm, of the University of East London, disagreed with the message that most obesity drugs do not improve quality of life or heart health based on this meta-analysis.

"A more accurate interpretation would be that while obesity medicines vary in their benefits and harms, several produce substantial weight loss, some demonstrate important cardiovascular benefits, and the quality-of-life findings depend heavily on how clinically meaningful improvement is defined," Merchant wrote.

"The findings do not show that obesity medications have no wider health benefits," agreed Marie Spreckley, PhD, of the University of Cambridge in England. "Rather, they highlight that while the evidence for weight loss is strong, evidence for some longer-term outcomes is still developing and differs considerably between individual medications."

In any case, the harms evident in the meta-analysis included gastrointestinal events with naltrexone-bupropion, oral semaglutide, orforglipron, and tirzepatide (RR 3.1 to 4.2). An increased risk of fatigue was also detected with naltrexone-bupropion (RR 8.9; absolute increase 331 per 1,000 people over 1 year), orforglipron (RR 3.4; 100 more per 1,000), and CagriSema (RR 3.2; 92 more per 1,000).

Notably, tirzepatide was associated with the largest reductions in fat mass (by 25.7%), as well as lean mass (by 8.3%).

As for next-generation GLP-1 medications (e.g., ecnoglutide, mazdutide, retatrutide), there was very low- to low-certainty evidence for their weight reduction effects to date.

"As the number of new drugs increases, physicians must now choose the right obesity treatment for each patient, individualizing the balance of benefits and adverse effects," wrote Hamlet Gasoyan, PhD, MPH, and Michael Rothberg, MD, MPH, both of the Cleveland Clinic, in an accompanying editorial.

"Right now, physicians and patients can choose among lifestyle modification, metabolic and bariatric surgery, and rapidly expanding pharmacotherapy options," they noted. "Physicians could use this up-to-date synthesis of evidence to guide their patients towards the treatments that are most suitable for them based on their preferences for outcomes and adverse events."

On the Science Media Centre website, Sonya Babu-Narayan, MBBS, clinical director at the British Heart Foundation, said that "the findings reinforce that GLP-1 medicines, prescribed by a doctor, are an important option for some people and that they work best alongside healthy eating, regular physical activity including strength exercises, and other healthy behaviors."

For their systematic review and meta-analysis, Li and colleagues selected studies that had randomized participants to at least 12 weeks of an obesity therapy versus control (lifestyle modification, placebo, or another drug). Eligible enrollees were adults with overweight or obesity, with or without cardiovascular or metabolic complications.

Study interventions included tirzepatide, CagriSema, ecnoglutide, mazdutide, retatrutide, semaglutide (oral and subcutaneous), survodutide, orforglipron, phentermine-topiramate (Qsymia), liraglutide (Saxenda), beinaglutide, naltrexone-bupropion, loxenatide, orlistat, exenatide, SGLT-2 inhibitors, dulaglutide (Trulicity), and metformin.

The 262 trials enrolled 99,791 eligible patients. Median age was 49 years, 63.3% were women, and median body mass index was 34.7. Follow-up typically lasted a median 26 weeks.

Beyond the GLP-1 medications, the appetite suppressant-anticonvulsant phentermine-topiramate was also tied to weight loss (mean difference -8.1%, 95% CI -9.7 to -6.5) in the study.

The quality-of-life analysis included 43 trials with 45,663 participants. For a clinically meaningful quality-of-life improvement, the investigators selected a threshold of 10 points on the Short Form 36 (SF-36), a self-reported patient survey that measures health-related quality of life, resulting in little to no effects detected among study drugs.

The SF-36 cutoff nevertheless remains "a judgement-based criterion," noted Merchant. "Alternative thresholds have been proposed in the literature and may have led to different interpretations of the data. Therefore, these findings should not be interpreted as evidence that patients experience no meaningful day-to-day benefits from treatment."

As for safety, the absolute risk increase for discontinuation due to any adverse event ranged from 19 (orlistat) to 94 (orforglipron) per 1,000 people over 1 year, Li's group reported.

Gasoyan and Rothberg cautioned that the meta-analysis did not include individual-level data, leading to an inability to adjust for individual factors that modify the effectiveness of specific drugs.

Disclosures

The study was supported by Chinese governmental and institutional grants.

Li had no other disclosures. Co-authors listed various ties to industry.

Gasoyan received grant funding from the National Cancer Institute and Cleveland Clinic. Rothberg disclosed consulting fees from the Blue Cross Blue Shield Association.

Merchant, Spreckley, and Babu-Narayan had no disclosed conflicts.

Primary Source

The BMJ

Source Reference: Nong K, et al "Comparative effects of drugs for adults with overweight or obesity: systematic review and network meta-analysis" BMJ 2026; DOI: 10.1136/bmj-2026-372161.

Secondary Source

The BMJ

Source Reference: Gasoyan H, Rothberg MB "Comparing benefits and harms of obesity drugs: a step towards individualised obesity care" BMJ 2026; DOI: 10.1136/bmj-2026-725349.

https://www.medpagetoday.com/primarycare/obesity/122142

Eye Specialists Flag Concerns About Pricey Lenses in Cataract Surgery

 Patients undergoing cataract surgery are often given the choice of a standard lens that's covered by insurance, or "upgrading" to a multifocal lens that uses newer technology -- at a much steeper out-of-pocket price, often around $5,000 per eye.

There's a perception that the more expensive version is better, but ophthalmologists are warning that's not necessarily the case.

Multifocal lenses aren't right for everyone, they told MedPage Today, and some patients who aren't good candidates can end up unhappy with the results, often leading to the need for revision surgery.

"If you have a perfectly healthy eye, you get a perfectly good surgery, and you hit the target exactly, it's amazing," said Christina Prescott, MD, PhD, who specializes in complex cataract and corneal surgery at NYU Langone Health in New York City. "But if your eye has any pathology, or your surgery doesn't go well, or you're not on target, then you lose a lot of quality of vision."

Ophthalmologists also raised concerns that economics may drive practices to steer patients toward the pricier lenses. And these practices may not be as meticulous about proper patient selection.

When Prescott's aunt was pitched a multifocal lens years ago, her physician equated it to car brands: "They said, 'Do you want the Toyota or the Lexus?' She said, 'I drive a BMW, so of course I want the Lexus version,'" Prescott told MedPage Today.

"She was a terrible candidate," she noted. "She had post-LASIK dry eye, a lot of astigmatism, and the lens was off target. She had to have one of my colleagues exchange it because it was the wrong choice for her."

Types of Multifocal Lenses

About 4 million cataract surgeries are performed in the U.S. each year, according to the American Academy of Ophthalmology.

About 80% of these surgeries are done with standard, monofocal lenses that are covered by insurance and provide patients with one type of vision, usually distance. Patients still need glasses for reading or other close-up activities.

Multifocal lenses give patients a broader range of vision, but they have to be paid for out of pocket.

Ophthalmologists now have about two decades of experience with these newer lenses, though the technology has evolved over time.

Prescott says the real boost in popularity came from the development of extended depth of focus (EDOF) lenses about 10 years ago, which offered an even wider range of vision and minimized complications like nighttime glare and starbursts that were more common with the original multifocal lenses. This often made driving at night a challenge.

Now there are trifocal lenses that offer even less glare, along with a larger range of vision, including distance, intermediate, and near, she said. Nighttime driving can still be affected, but to a lesser extent.

Paying extra to be able to toss the reading glasses is appealing to some patients. But they shouldn't do it if they're not a good candidate, she warned.

The Right Candidate

Patients with conditions like macular degeneration, epiretinal membrane, or diabetic retinopathy are not good candidates for multifocal lenses.

"Retinal problems do not let the lens function as it's supposed to function, and as a result, they don't have the vision they were expecting," Dimitra Skondra, MD, PhD, a retinal surgeon also at NYU Langone Health, told MedPage Today.

Skondra said she has seen patients from New York travel to Florida for the winter, where they're pitched cataract surgery with these premium lenses. When they return to New York, they're disappointed with their vision.

"If things would have been explained to the patient before, many of them probably would have made a different choice," she noted.

Other conditions can impact the performance of multifocal lenses, Roberto Pineda II, MD, of Mass Eye and Ear in Boston, told MedPage Today, including corneal issues such as irregular astigmatism, or "maybe a scar from a minor infection with a contact lens in the distant past, or prior laser vision correction surgery."

"I do a lot of lens exchanges for unhappy patients," added Pineda, who specializes in corneal, refractive, and complex cataract surgery. "The technology works well, but it doesn't work well for everyone."

He said he completes a thorough ocular biometry for every eye ahead of cataract surgery, to calculate the correct power of the lens for the patient. He also does a macular optical coherence tomography to rule out retinal diseases and get a thorough evaluation of the anatomic appearance of the macula and fovea.

"We spend a lot of time doing preoperative testing," he said. "In the past we didn't do that as much because it wasn't really needed, but with the new lenses we have to identify any pre-existing condition that might impact the performance of the lens."

High-Volume Practices

It's not clear that all patients receive such thorough preoperative testing, experts warned.

Sometimes patients only receive information about lenses from a "lens coordinator," rather than a physician.

"As part of the new era of high-volume practices that do many different lenses ... the consent process is a little more complicated and more time-consuming than it was 20 years ago," Skondra said. "Some of the doctors ... designate someone in the practice so they get a bit of training and experience discussing the different lens options, but obviously they are not the doctor."

Prescott said she sees "a lot fewer patients per day by design than a lot of cataract surgeons do, because I tell people the longest part of this whole process is talking about lenses and figuring out the right lens for you."

"I don't think a lot of people spend that much time on that part of it because they're seeing a lot of patients, and they have their private practice, they have overhead, and they need to see a certain number of patients," she added.

Pineda pointed out that sometimes patients only see the surgeon on the day of surgery.

"If the surgeon is doing 20 cases, they have to look through all of those cases and see if there are any issues ... that would not make them a good candidate," he said. "Telling them on the day of surgery that they're not a good candidate -- patients don't like to be told that."

"I do think that sometimes economics wins," Pineda noted. "There's a push to encourage patients to select one of these new lenses."

Prescott suggested that's bad for business overall. "In the long run, that's worse for the multifocal lens companies," she said. "If they're put only in patients who are appropriate candidates, I think they'd be considered a wonder of modern technology."

She noted that her aunt's poor results with her multifocal lens almost dissuaded her mother from getting one. But her mother, who was a much better candidate, ultimately got an EDOF lens and has been thrilled with it.

"We're kind of hurting ourselves by overdoing it," she said.

https://www.medpagetoday.com/ophthalmology/generalophthalmology/122111

'Oversight Needed on Physician-Assisted Suicide for Hospice Patients, Lawmakers Say'

 When it comes to the use of physician-assisted suicide for hospice patients, more guardrails are needed to avoid discrimination against the vulnerable and disabled, several members of Congress told the Trump administration.

"Physician-assisted suicide raises significant informed consent issues as well as concerns about disability and age discrimination," wrote senators James Lankford (R-Okla.) and Tim Kaine (D-Va.) and representatives Greg Murphy, MD (R-N.C.), and J. Luis Correa (D-Calif.) in a letter Thursday to HHS Secretary Robert F. Kennedy Jr. "The vast majority of patients receiving physician-assisted suicide are enrolled in hospice ... This poses challenges for HHS and CMS' regulation of patient health and safety within the hospice program."

In the letter, which was also sent to CMS Administrator Mehmet Oz, MD, MBA, the lawmakers urged "HHS and CMS to implement reporting requirements in the hospice program to monitor physician-assisted suicide for discriminatory practices against vulnerable populations." Specifically, the letter requested that HHS and CMS "establish reporting requirements within hospice programs regarding physician-assisted suicide" and to consider monitoring physician-assisted suicide practices for:

• Discrimination against individuals with disabilities, older adults, and other vulnerable populations
• Proper disposal of unused medication and prevention of drug diversion
• Insurance denials of life-sustaining medical care that offer to cover physician-assisted suicide drugs instead
• Drug complications
• Consistency of drugs prescribed "off-label" for use in physician-assisted suicide
• Compliance with federal restrictions on using funds, directly or indirectly, for healthcare items or services for physician-assisted suicide

"All hospice patients -- regardless of disability, age, or financial means -- deserve compassionate end-of-life care that is free of coercion and discrimination," the authors concluded.

"Hospice should be a place of compassion, comfort, and care, where the suffering are surrounded by loved ones and quality healthcare, not a place where they feel quietly pressured to end their lives through assisted suicide," Lankford said in a press release. "Federal law is clear that taxpayer dollars cannot pay for assisted suicide, and discrimination against the aged and disabled is prohibited. HHS and CMS have a responsibility to make sure vulnerable people are protected. We're simply asking them to do that job."

Murphy took a stronger stance. "As a practicing physician of 35 years, I have dedicated my career to saving lives and comforting my patients," he said in the release. "The oath all physicians take is 'to do no harm.' Physicians who take part in assisting suicide are breaking that oath. It is a great tragedy that people feel that life offers them no recourse other than to end their lives."

"Rather than suicide we should invest more in palliative care and hospice which are much more acceptable forms of medical care," he said. "Sadly, abuses such as the lack of informed consent and discriminatory practices have occurred, and patients and their families have been wronged. The House of Medicine should not participate in assisted suicide when we have other humane alternatives to offer."

John Maa, MD, a San Francisco surgeon, said in an email he thought the letter was helpful "in the current state of conflicting and variable state laws without federal legislation on this topic."

"There needs to be assurance of safe disposal of the medications [as well as] an understanding of the financial factors at play and the costs patients bear, the historical trends, the costs to the patient and the most impacted populations," he wrote, adding that "congressional action on the topic would be helpful to ensure that all relevant laws are complied with, to protect those patients who choose to utilize this process, and to ensure that pharmacy practices are conducted in the safest manner (some require pickup of the meds and delivery by a physician, while others send by mail). A process as complex as this should have federal oversight."

Maa recently wrote for MedPage Today about being present when a friend underwent physician-assisted suicide -- also known as medical aid in dying, or MAID -- following a long battle with pancreatic cancer. He said that a few weeks later, as a delegate to the American Medical Association (AMA), he chaired a discussion held during an AMA committee meeting about a request to formally change the way the AMA referred to the procedure from physician-assisted suicide to MAID. "Some opposed physician-assisted suicide for ethical and religious reasons, or viewed it as violating the Hippocratic Oath ... Others praised the intent to alleviate suffering and restore patient autonomy."

AMA policy opposes physician-assisted suicide; eventually, the delegates voted in favor of keeping the current name and continuing the AMA's opposition.

"Fundamentally, the question remains whether physicians should be involved at all," Maa concluded. "Perhaps one option is to end physician involvement after certifying that a patient qualifies, and delegate the remaining steps to others like a pharmacist or the coroner. Physicians should instead focus on supporting terminal patients and finding new cures to push the limits of medical knowledge."

https://www.medpagetoday.com/publichealthpolicy/ethics/122151

Leftists Celebrate Murder Of Conservative British Politician

  by Steve Watson via Modernity News,

The savage killing of 78-year-old Reform UK spokeswoman Ann Widdecombe has unleashed a torrent of vile celebration from left-wing activists, revealing the depths of ideological hatred among the left in the UK.

Widdecombe, the outspoken former Conservative MP and prisons minister, was found dead with serious injuries at her Dartmoor home, prompting an immediate murder investigation by Devon and Cornwall Police.

Police keenly informed the public that a 26-year-old white British man has been arrested on suspicion of the crime. The incident is not being treated as terrorism, but the public reaction - particularly from leftist corners - has shocked many and exposed a chilling tolerance for violence against political opponents.

Detective Chief Inspector Ilona Rosson emphasized the tragedy: "This is an extremely tragic incident and our thoughts are very much with the family and friends of Ann Widdecombe at this difficult time. Our murder enquiry is in its early stages but moving at a significant pace." The force urged against speculation while deploying resources for house-to-house inquiries.

What followed was a mask-off moment. Rather than universal condemnation, platforms like Bluesky - often touted as a "kinder" alternative - filled with jubilation, with users openly celebrating the death of the elderly conservative.

The stream of derogatory and celebratory posts include accusations that Widdecombe was a "racist old bitch" and a comment that "Science produced an answer to Ann Widdecombe," referencing her past comments on gender ideology.

Users shared cartoons, GIFs, and barbs that treat her violent end as punchline or progress.

Widdecombe served as MP for Maidstone for many years and held roles including Minister of State for Prisons and Shadow Home Secretary. A staunch Eurosceptic, she backed Brexit and later joined Reform UK. Her socially conservative views - opposition to abortion, support for traditional marriage, and criticism of leftist policies - made her a lightning rod. Yet she commanded respect for consistency and wit, appearing on entertainment shows while maintaining principles.

Leftist celebrations aren't anomalies; they stem from years of framing conservatives as villains. Terms like "bigot" or "racist" dehumanize, paving the way for glee at misfortune. This echoes reactions to other figures, revealing a worldview where ideological purity trumps basic humanity. Platforms shielding such content while censoring dissent exacerbate division.

Critics rightly note two-tier dynamics. Emphasis on the suspect's description here contrasts with vagueness elsewhere, fueling skepticism. Broader failures - open borders straining cohesion, cultural erosion, elite dismissal of native concerns - create fertile ground for extremism. Widdecombe warned against these trends. Her death amplifies those warnings.

Reform UK figures now face heightened risks. Leader Nigel Farage's security needs underscore the stakes. Media and activist demonization of "the right" as fascistic contributes to a climate where violence seems justifiable to some.

Widdecombe's passing, tragic as it is, spotlights the stakes. A principled voice silenced violently amid cheers reveals civilizational fragility. Defenders of freedom - pro-sovereignty, anti-woke, pro-debate - must push back. The alternative is descent into the very barbarism celebrated by the unhinged.

https://www.zerohedge.com/political/leftists-celebrate-murder-conservative-british-politician

Afghan Asylum Seeker Walks Free After Sexually Assaulting Multiple Young Girls At German Pool

 by Steve Watson via Modernity News,

A 21-year-old Afghan asylum seeker stands accused of sexually assaulting at least four girls between the ages of 12 and 14 at the Bud Spencer outdoor pool in Schwäbisch Gmünd, southwestern Germany.

According to police accounts detailed in German media coverage, the suspect touched the victims on their buttocks or thighs and attempted to pull down their bikini bottoms. In one instance he reportedly tried to penetrate a girl's intimate area with his fingers. The girls resisted and fought him off before he stopped.

Police reports confirm the attacks occurred in the adventure pool area, yet an arrest warrant was suspended under limited conditions that do little to shield the public from further risk.

A 21-year-old Afghan asylum seeker has been allowed to walk free after sexually assaulting at least four girls, aged 12-14, at the Bud Spencer outdoor pool in Schwäbisch Gmünd, southwestern Germany.

He inappropriately touched the girls, attempted to remove their bikini bottoms,... pic.twitter.com/ohcn194Fl7

— Visegrád 24 (@visegrad24) July 8, 2026

Authorities have indicated they do not rule out additional victims and continue to seek witnesses. The suspect was arrested, but a judge suspended the arrest warrant subject to conditions, including a ban on entering public swimming pools. Incredibly he has walked free pending the outcome of the investigation.

This case fits a recurring pattern of sexual violence and harassment targeting women and children in German public swimming facilities.

Prior investigations have laid bare the scale of the problem through official statistics and internal assessments that reveal stark disparities in perpetrator backgrounds.

Research established that 65 percent of sexual assault suspects in swimming pools were foreigners.

Separate analysis showed foreigners vastly overrepresented in sexual assaults as well as other crimes committed at these locations.

Another examination concluded that German authorities have not been fully honest about the identities of those assaulting children at swimming pools, with patterns of omission in official and media descriptions.

Coverage of the Schwäbisch Gmünd incident itself drew attention to selective reporting practices. Some German outlets described the suspect only as a 21-year-old man without noting his Afghan nationality, consistent with earlier criticisms of incomplete disclosure around perpetrator backgrounds in similar cases.

An internal assessment cited in reporting on the broader trend confirmed a surge in sex crimes at bathing establishments. It stated particular concern over rape and the sexual abuse of children, noting that the perpetrators are for the most part immigrants.

The president of the Federal Association of German Swimming Champions previously warned that he could no longer recommend families visit outdoor pools on weekends, adding that he would be acting irresponsibly if he took his own three grandchildren.

These documented realities have prompted concrete policy adjustments at some facilities.

Certain German swimming pools have begun barring visitors who cannot speak German, citing safety concerns tied to communication failures and behavioral patterns that complicate supervision and intervention in shared spaces.

The conditions imposed in the current case - a pool ban while the suspect otherwise remains free - illustrate the narrow tools available under current practices.

A targeted restriction does nothing to address potential risks in other public settings or to deter future incidents involving the same individual.

Girls who fought off the attacker at the adventure pool now rely on the hope that he complies with the limited order while the investigation proceeds.

Recurring episodes at pools, schools, and other everyday venues have exposed the downstream effects of rapid demographic change without corresponding integration or enforcement standards.

Cultural and language barriers frequently surface in official descriptions of incidents, yet public discourse often treats acknowledgment of these factors as off-limits. The result is a cycle where statistics accumulate, incidents repeat, and responses remain incremental.

Families seeking ordinary recreation at public pools encounter an environment shaped by these accumulated failures. The statistical overrepresentation, the documented reluctance to identify patterns clearly, and the narrow conditions placed on released suspects combine to shift the burden of vigilance onto parents and children themselves.

Official appeals for witnesses after each new case underscore how many incidents may go unreported or unresolved.

The Schwäbisch Gmünd events add to a ledger of cases stretching back years, where similar profiles of suspects and similar gaps in transparency have appeared repeatedly.

Germany's experience with these issues at swimming pools offers a clear window into the practical limits of policies that prioritize volume of migration over selection, vetting, and assimilation.

The pattern of incidents, the data on disparities, and the incremental restrictions now appearing at some pools all point to the same conclusion: current approaches have produced measurable costs in security and social cohesion that continue to mount.

https://www.zerohedge.com/geopolitical/afghan-asylum-seeker-walks-free-after-sexually-assaulting-multiple-young-girls-german