Category Archives: General Health

TRIUMPH-1: Impressive Results for Obesity Treatment with Triple Agonist Retatrutide

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AA Jastreboff et al. NEJM 2026; DOI: 10.1056/NEJMoa2604169.
Retatrutide, a Triple Hormone Receptor Agonist, for Treatment of Obesity

Background: Retatrutide (LY3437943) is an agonist of the glucose-dependent insulinotropic polypeptide, glucagon-like peptide 1, and glucagon receptors.

In 2023, “a phase 2 trial involving participants with obesity, once-weekly subcutaneous retatrutide (at a dose of 12 mg) resulted in a mean weight reduction of 24.2% at 48 weeks24 and improved multiple cardiometabolic measures, including waist circumference, systolic and diastolic blood pressure, glycated hemoglobin, and lipid levels.” This randomized, double-blind phase 3 trial examined a larger cohort (n=2339) with respect to obesity as well as knee osteoarthritis and obstructive sleep apnea in participants with obesity without diabetes.

Key findings:

  • Obesity at 80 weeks: The mean percent change in body weight in the retatrutide groups at 80 weeks was −17.6% (4-mg dose), −23.7% (9-mg dose), and −25.0% (12-mg dose) versus −3.9% in the placebo group. The 12 mg dose resulted in a mean change of -28.3% (according to the efficacy estimand) at 80 weeks
  • Obesity at 104 weeks: In the extension phase of the trial, retatrutide treatment was associated with a mean weight reduction of up to 29.9% (treatment-regimen estimand) and 30.3% (efficacy estimand) at 104 weeks
  • Osteoarthritis: the mean change in the WOMAC pain subscale score (in points) at week 80 for the knee osteoarthritis basket was −3.5 and −3.6 with retatrutide 9 mg and 12 mg, respectively, and −1.9 with placebo. Treatment with retatrutide resulted in a reduction in pain of up to 61.6%
  • Obstructive sleep apnea: the mean change in the AHI events per hour at week 80 was −34.3 and −31.7 with retatrutide 9 mg and 12 mg, respectively, and −9.9 with placebo; this resulted in a mean decrease in AHI events per hour of up to 57.3% (hybrid-treatment estimand)
  • Limitations of the trial include the absence of an active comparator, which may have contributed to greater attrition in the placebo group,
Panel A shows the percent change in body weight from baseline to week 80 (controlled for type I error). The curves on the left show changes from week 0 to week 80 on the basis of observed means during treatment according to the efficacy estimand data-point set
Panel B shows the percentage of participants with normoglycemia, prediabetes, and type 2 diabetes at week 80 among the participants who had prediabetes at baseline

My take: Retatrutide was so effective, even at lower doses, that use of the lowest effective dose to achieve treatment goals may be a useful strategy rather than expecting to maximize the dose in all individuals. While the results are terrific, access and affordability remain important issues with these newer obesity medications.

Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

“Many Surgical Interventions Are Little Better Than Placebo”

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The Economist, 9/23/26. Many surgical interventions are little better than placebo (behind paywall). Thanks to my sons for sharing this article with me.

An excerpt:

“EACH YEAR, according to the World Health Organisation, over 300m operations are conducted worldwide. Patients in the rich world are more likely to go under the knife—about 60% of people in England are expected to undergo surgery at least once in their lifetime. Some of these procedures are clearly life-saving, such as organ transplants and emergency Caesareans…

Answers have long been hard to come by, in part because few randomised controlled trials (RCTs), the gold-standard type of research used to assess medications, were conducted on surgical procedures. That made it difficult to know if patients got better more often with surgery than they might have without. This is now changing. The number of surgical RCTs funded by Britain’s National Institute for Health and Care Research increased from 34 in 2011 to 188 in 2023…

Most striking, the data show that some widely used surgical procedures, such as spinal fusions and rotator-cuff repairs, have effects indistinguishable from placebo or non-surgical care such as physiotherapy…

Worse, some types of surgery may do more harm than good. A trial in Britain found that prostate-cancer surgery had no effect on patient mortality 15 years on, but worsened sexual and urological problems. A Finnish trial of a common knee procedure, meanwhile, concluded that patients who had real surgery had more problems in the affected knee ten years on than those who had had sham surgery (anaesthesia followed by a superficial incision)…

If so many operations are unnecessary, how to explain the fact that patients often leave the operating table feeling better? In a study published in 2022 in JAMA, a journal, researchers pooled data from 100 surgical trials covering 32 interventions. They found that two-thirds of the improvement patients felt after surgery was due, on average, either to the body healing on its own or else to the placebo effects of feeling cared for and prepped for surgery. Only one-third of the benefit, in other words, came from the procedure itself…

Natural healing is also powerful, if slow-acting. In the 2022 study in JAMA…the placebo effect could explain only a small part of the improvement in the sham-surgery group. Most of the benefit came instead from natural improvement…

Surgeons continue to perform some operations that have been shown to be no better than placebo surgery at the same rate as before. They find it hard to believe that something which they have been doing for years and seems to help their patients is, in fact, useless…

Surgeons who have been doing a procedure for years also tend to overestimate its benefits, says Stefan Lohmander from Lund University, in Sweden, because the patients who return for check-ups are mostly those who got better. Moreover, many of these returning patients do not want to disappoint their doctors…

The nature of a country’s health system also plays a role. Disfavoured operations decline faster in countries where surgeons are salaried, as in Britain and Scandinavia, than in countries such as America where they are paid per operation and act as small businesses. Shoulder surgeries to remove a bone spur fell from 28,000 in Britain in 2016-17 to 5,720 in 2019-20, after trials found that the procedure was no better in alleviating pain than sham surgery. In America the procedure remained popular…

But it is not just surgeons who need to trust the data: a growing number of patients insist on surgery on the basis of inconclusive tests. ..A growing number of studies, in fact, show that the abnormalities in knees, backs and shoulders that orthopaedic surgeons try to fix are very common in people who have no symptoms at all. But the promise of a quick fix is hard to resist.“

My take: This article reminds me of two expressions:

  • “Don’t just do something stand there”
  • “If you follow my advice, you will get better in 3 months. If not, it will take 90 days.”

The first expression I heard during my fellowship from Dr. Balistreri. With medications, diagnostic procedures, and surgery, many times natural healing is as effective as interventions and less costly.

Related blog posts:

Wekiva Springs State Park. Apopka, FL. I did go swimming here despite the warning.

Declining Child Health in the U.S.

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CB Forrest, N Halfon. N Engl J Med 2026;395:1147-1149. Declining Child Health in the United States — Addressing the Developmental Ecosystem

This commentary paints a broad picture of declining health for U.S. children and what is needed to change the trajectory. Here are some excerpts:

Child health has been deteriorating in important and alarming ways in the United States…over the past two decades.1 Infants, children, and adolescents in the United States are 80% more likely to die than their peers in other high-income countries…77% of Americans 17 to 24 years of age would be ineligible to enlist in the U.S. military without a waiver, for reasons including obesity, mental health problems, and other medical conditions.2…

Researchers, policymakers, and the media have tended to attribute these trends to independent challenges — an obesity crisis, a mental health crisis, loneliness, gun violence — with distinct programmatic responses and potential remedies supported by separate advocacy groups and funding streams. But many of them have common origins and drivers…Interventions that target a single risk factor may relieve immediate suffering but will generally be insufficient to change developmental ecosystems in ways that can reverse generational declines in health…

At the base of the iceberg are a developmental ecosystem’s foundational values, which are often expressed in shared narratives about childhood: that raising children is chiefly a private responsibility, that markets are the fairest arbiters of who can be healthy…and that public support should be provided for children’s health programs only in exceptional circumstances…

The influence of these beliefs can be observed in the choices that society has made, including spending less than peer countries on early-childhood programs, opting not to regulate digital platforms that profit from the commodification of children’s attention, and organizing health care systems around the treatment of illness, rather than the promotion of healthy development.

The Elephant Rock is a natural rock formation located on the island of Heimaey in the Westman Islands

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More on Measles (October 2026)

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Trisha Pasricha, Washington Post 10/5/26: Measles can erase up to 73 percent of your immune system’s memory

An excerpt:

“My sister says there’s no real difference between a child getting the measles vaccine and just catching measles, since either way the child ends up immune. Is she right?

I wouldn’t describe it as “just catching measles.” In the United States, about 1 in 5 unvaccinated people who get measles is hospitalized, and 1 to 3 of every 1,000 children infected will die, according to the Centers for Disease Control and Prevention…

Children with measles become more susceptible to other infections like ear infections or diarrhea. Today, the most common cause of death among young children with measles is pneumonia…

In a study published in Science in 2015, researchers analyzed decades of childhood mortality data from the United States, England and Wales, and Denmark. They noticed that in the pre-vaccine era, when measles cases spiked, deaths from other infections rose, too — and not just immediately but for the subsequent two to three years…When the measles vaccine arrived, and measles cases fell, deaths from other infectious diseases fell along with them. The scientists estimated that where measles was common, measles infections could have been implicated in as many as half of all childhood deaths from infectious disease.

Center for Infectious Disease Research and Policy, University of Minnesota: “Pennsylvania confirms more than 1,000 measles cases. Nationwide, the Centers for Disease Control and Prevention (CDC) reported 3,887 measles cases as of October 2… Health department officials in South Carolina also have said that the state likely had more measles cases this year than the official count of 997. Doctors in South Carolina aren’t required to report measles-related hospitalizations, according to a report from ProPublica.”

Measles: 99% of the cases (n=1004) are in the unvaccinated which represent 7% of Pennsylvania’s population. Graph courtesy of Neil Stone, MD (via X). All of the deaths have occurred in the unvaccinated.

Related blog posts:

PrEggNut Trial: Pregnancy Egg and Peanut Intake Didn’t Prevent Allergy

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DJ Palmer et al. N Engl J Med 2026;395:1090-1099. Trial of a Maternal Diet Rich in Eggs and Peanuts to Reduce Infant Allergy

Methods: For “The PrEggNut Trial,” a multi-site, randomized trial, “pregnant women whose unborn child had at least two biologic family members with medically diagnosed allergic disease were eligible to participate. Participants were assigned in a 1:1 ratio to follow either a diet high in eggs and peanuts that included at least 6 eggs and 60 peanuts per week (high egg–peanut group [n=1070]) or a standard (control) egg and peanut diet that included no more than 3 eggs and 30 peanuts per week (standard-diet group [n=1067]), from before 23 weeks’ gestation until 4 months postnatally during lactation. The primary outcome was IgE-mediated egg or peanut allergy in the infant at 1 year of age.

Key findings:

  • There was no significant difference in the percentage of infants with IgE-mediated egg or peanut allergy between the maternal high egg–peanut group (83 of 1066, 7.8%) and the standard-diet group (89 of 1064, 8.4%) (relative risk, 0.93; P=0.65)
  • A potential limitation of the trial was the lower-than-anticipated prevalence of egg or peanut allergy (8% actual vs. 16% anticipated)

My take: Increased exposure to eggs and peanuts during pregnancy did not reduce allergies in infants. Exposure during infancy, however, can reduce the rates of allergies.

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Incredible Video of Lung Cell Cilia

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Stella Raine Chu, NY Times 9/17/26: Microscopic Videos That Show the Invisible Wonders Around Us

“The winners of this year’s Nikon Small World in Motion competition showcase the wiggly, feathery, undulating beauty of invisible life.” In total, there are seven short videos featured.

1st place: Abnormal beating of airway cilia from a child with a disease called primary ciliary dyskinesia. Cilia are about 1/100th the width of a human hair.

Addendum: **A reader’s comment notes that the winning entry is ” being re-evaluated following criticism from other scientists that it was made with AI.” Here is an article from the BBC on this: Link: Tiny image sparks big backlash in Nikon photo contest

“Being a Doctor Will Never Be the Same After A.I.”

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Rachael Bedard. NY Times 9/25/26: Being a Doctor Will Never Be the Same After A.I.

An excerpt:

“I have a confession: A.I. is making me a better doctor. And I worry that it’s making doctors-in-training worse…

I already use the technology in my practice all the time…This summer, I used an A.I. tool — a platform called OpenEvidence, accessible only to health care providers — to help me choose antibiotics for one patient and to interpret unusual bloodwork for another. A.I. reminded me to consider migraines when a woman presented with dizziness. ..

Almost every month, I’m confronted with a complaint or syndrome that I don’t recognize. I’m confident in my mastery over what doctors do — history-taking, reasoning, communicating. I’m less confident about my continued mastery of an ever-evolving universe of facts. Now, the chatbot in my pocket reassures me that I will always know enough, or have access to the cloud-based intelligence that generally does.

All of my students and residents also use OpenEvidence, however, and I worry about the consequences of introducing such a powerful decision aid so early in their careers. Not only have they memorized less than I’d like, but they can seem almost passive in their relationship to their machines…

OpenEvidence is trained exclusively on peer-reviewed evidence and guidelines, and includes citations for all its claims…To use the app well, you must stay skeptical as you scroll…

I’m surprised by how much I learn from, and enjoy, these interactions. More important, my patient care has improved as conversations with the agent push my thinking beyond its usual limits…

Adam Rodman, a physician and A.I. researcher at Harvard Medical School,… said he shared my concern that trainees aren’t benefiting from “productive struggles” as much as their predecessors. “In experienced hands, decision support might cause a little de-skilling, but a little de-skilling probably doesn’t matter much to you,” Dr. Rodman told me. “But if you do that to somebody who has much less skill, the cognitive offloading can cause never-skilling”…

Current doctors-to-be may be the most adversely affected generation when it comes to A.I. They’re training before we know enough about how to teach them well in this new paradigm.

My take: In all aspects of learning, not just medicine, using AI shortcuts may make learners increasingly dependent on their devices, undermine their judgment and hinder developing their own voice. How to best train individuals in this new era remains unclear.

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Svörtuloft Lighthouse is located at the westernmost tip of the Snæfellsnes Peninsula in West Iceland. It is perched atop a 2.5-mile stretch of pitch-black volcanic lava cliffs.

Breaking the Silence: A Doctor’s Struggle with Mental Health

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T Khan et al. NEJM 2026; 395: 529-531. Doctor’s Dirty Little Secret — The Cost of Silence

An excerpt:

No one would suspect that for the past month I’d been plotting my death. Death felt like the only way to let go of the fear and exhaustion that was swallowing me whole…

“You know we don’t lock people up just for having suicidal thoughts anymore, right?” The on-call emergency psychiatrist’s tone, though comforting, was edged with frustration…

“Most of us have had thoughts of suicide at some time in our careers,” she said plainly. “It’s an occupational hazard — like a needlestick or missing your kid’s recital.”

With those matter-of-fact words, she named the doctor’s dirty little secret: we are human. But we believe this admission could cost us everything. That curbside consult saved my life. For the first time in a long while, I didn’t feel alone.

I’d been an emergency doctor for nearly half my life, running on a steady drip of cortisol. By my 40s, my body struggled to keep pace with the demands of the job…

I was responsible for everyone and everything all at once — crisis, illness, intoxication, and circumstance colliding, each person having been carried to me by whatever fear or fate had gripped them. I absorbed the frequent interruptions along with the urgency and blame, until the weight of it all settled as a constant heaviness in my chest…

I was deep in burnout.

And I am not alone. In the United States, female physicians die by suicide at more than 2.27 times the rate of women in the general population, and male physicians at 1.41 times the rate of men in general.1 These statistics are not abstract. They reflect the real suffering of physicians, who are also children, spouses, parents, siblings, and friends, and they reflect a story I never expected would one day become my own. The data challenge the enduring myth that doctors are somehow superhuman…

Despite copious literature on burnout, effective solutions remain scarce…many of us find deep meaning in our work, which fuels perseverance even in the face of adversity…

It took crashing into a wall for me to understand the delicate dance between grit and resilience. Grit is the pedal that drives us forward; resilience is the wheel that helps us change course. Resilience guided me to seek help — which was surprisingly difficult to find…

I kept my license, my family, and my life — for now. But many physicians aren’t as fortunate. Shame, stigma, and institutional failures may keep them silent, but silence is not strength. And asking for help is not a betrayal of the profession.

Related article: A Albert. Gastro & Endo News July 2026. Listen to Your Youngers: Why Gen Z Doctors Refuse to Die for RVUs Open Access! “I think we do better by our patients when we do better for ourselves…The younger generation isn’t “killing” medicine. They’re trying to survive it. They’re realizing that an exhausted, dehydrated doctor who hasn’t seen sunlight in three days isn’t “dedicated”—they’re a liability.”

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The Politicization of Science and Outcomes for Health Care

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Yesterday’s blog post highlighted how the current policies are leading to a brain drain, undermining economic advangages and harming our ability to improve outcomes for patients.

Today’s post summarizes a recent editorial by the NEJM editors (NEJM 2026; 395: 187-188. The OMB and the Politicization of Science) that drills down on three specific proposals by the OMD to change research policy.

An excerpt:

“For decades, the Soviet Union promoted the unorthodox views of Trofim Lysenko, an agronomist who used his close ties to the political leadership to spread misinformation denying Mendelian genetics. What followed was a disaster: many years of poor harvests based on unsupported science and suppression of the teaching and practice of modern genetics throughout the Soviet bloc. A similar threat now hangs over U.S. science…

The rule changes that the White House Office of Management and Budget (OMB) recently proposed to the Health and Human Services (HHS) grant process would drastically change this process. There are too many objectionable aspects of these proposals to discuss here. But three are particularly striking. Political appointees would be able to make funding decisions and could ignore the advice of independent scientists. They could also stop funding midway through the promised grant period. And they would institute new rules, including rules severely limiting foreign interactions…

Expert, independent peer review of grant applications is essential for directing NIH dollars to research that has the greatest potential for advancing science and improving health. Selecting the most promising research is an enormously complex and challenging undertaking…

The OMB proposal to permit political appointees to discontinue funding of ongoing grants at any time, without cause, would have serious adverse consequences for the research enterprise and for patients…the gold standard of evidence is the randomized, controlled trial (RCT). The RCT’s methods minimize the influence of bias and preconceived notions. However, this type of trial often takes years to conduct…If a decision to stop funding the trial occurred at year 4 for political rather than scientific reasons, what would happen to patients who were enrolled in the study at that time? How would longer-term safety and efficacy observations be made?…Can physician–investigators ethically enroll a patient in a trial if ongoing funding for the trial is uncertain?

There would be substantial adverse effects on researchers as well as patients. Why would a basic science investigator start a line of investigation that might take years to complete if the funding for it could be cut at any moment, without cause?…A corrosive consequence of such an arbitrary funding process would be the diminishment of the U.S. workforce of clinical and basic science investigators — and it would ultimately harm biomedical innovation and cutting-edge patient care…

The proposed rules would also severely limit foreign research partnerships, requiring political approval of international collaborations…Broad global collaboration has led to…studies [which] can be completed years earlier than they would be otherwise, at a fraction of the cost, bringing earlier and greater benefits to all affected people, including people in the United States. Aren’t we better off addressing Ebola, tuberculosis, or screwworm before they spread to additional communities?” 

My take: Allowing politicians to arbitrarily choose which research to fund rather than those with the greatest merit will lead to a poor harvest of scientific advances for all of us. This would, however, enable a select few to benefit from their corrupt connections to steer more money into their greedy pockets.

Boardwalk at Arablia Mountain Trail