The Question vs. Answer Disparity Factor

A recent post here inquired, “Are crucial questions being addressed?” One of them is, “Why is it even necessary to ask that particular question?”

Whenever a major story hits the news, the same phenomenon can be observed. Generally, the public hears an awful lot about one aspect, or a couple of major aspects, of the event. Some in-depth, long-form reporting still exists, of course, but most people have neither the time nor the inclination to pursue any topic with the rigor of either a Ph.D. candidate or a law enforcement officer.

About the GLP-1 receptor agonists and the other concoctions with similar intent, questions litter the landscape. There are some whose answers the drug companies love to flaunt in everybody’s faces, and then there are questions concerning some aspects of testing that they are not particularly anxious to discuss in any public forum.

When it comes to the usefulness of the new weight-loss drugs, a number of matters seem to have been under-discussed — except by such journalists as Lisa Jarvis, whose expertise encompasses the pharmaceutical industry and the fields of biotech and health care.

For example:

Among the 60 trials for tirzepatide listed on, just one seems designed to understand whether a lower dose can be as effective as a high one at maintaining weight loss. But clearly more studies will be needed guide what long-term treatment will look like.

Many published scientific papers wind up with the same prediction/recommendation: basically, the world needs more information. This is only natural. The researchers portray themselves as conscientious explorers who do not possess the hubris to claim omniscience. Potential funders are put on notice that more investment will be needed for further study. Also, the disclaimer probably helps to fend off lawsuits.

There is always more to learn. Which patients will be harmed by this discovery? Which stand to benefit most? How much will it cost them? Who will pay the bill? Which essential meds does it clash with? Can members of the team that wrote this paper continue to do meaningful work in this area?

It is easy to imagine the commonly repeated formula adopted as a catchphrase among students:

“Should we grab another six-pack?”
“More studies will be needed.”

What else do we probably not know enough about?

Some currently pressing questions are wide-ranging, and affect many different segments of the economy and of society as a whole. Jarvis mentions potential effects on the food and beverage industries, including both manufacturers like the mega-corporations that make the stuff, and providers such as grocery stores and restaurants.

The airlines and the clothing industry will feel the implications. Insurers (including the government) may be happy to know that treatment with the new drugs can prevent or alleviate such events as heart attack, kidney failure, or stroke.

But considering the price tag, is it worth it to them to encourage prescriptions and prevention, over the traditional system of simply mopping up after medical calamities? The entire field needs to pay attention, as well as such specialized segments as bariatric surgery. And, obviously, the pharmaceutical empires stand to become more powerful than ever before. The journalist reports that “Mounjaro alone could bring in over $50 billion each year. ”

Your responses and feedback are welcome!


CBT, iCBT, and Virtual Reality in the Battle Against Eating Addiction


There’s been a lot of talk of using the GLP-1 agonists for weight loss, both adults and children. However, there’s a solid case that they won’t replace interventions like 12 steps, displacement theory-based interventions, good old exercise, and Cognitive Behavior Therapy (CBT). Let’s discuss CBT — the internet-based CBT (iCBT) in particular.

Studies show promising results

According to an article published in the Journal of Affective Disorders and reposted on ScienceDirect, patients with binge spectrum eating disorders often struggle to access standardized treatment. iCBT significantly improves clinical symptoms associated with these disorders. One meta-analysis demonstrates the clinical efficacy and acceptability of iCBT for binge spectrum eating disorders, “significantly [improving] clinical symptoms associated with these disorders.”

The meta-study searched databases including PubMed, Embase, Web of Science, Cochrane Library, and PsycINFO, collecting relevant information up to August 2023, shaping it into 11 randomized controlled studies. Results showed that iCBT “significantly improves pathological eating behaviors, reduces binge episodes, alleviates depressive and anxious emotions, and enhances self-esteem in patients.” A PubMed article shared on ResearchGate also reported positive results, stating that CBT “is the leading evidence-based treatment for bulimia nervosa.”

Virtual reality as a tool to fight obesity

The Obesity Care Clinic published a lengthy article about the potential of virtual reality (VR) as a tool to fight against obesity, noting that “traditional approaches like dietary interventions and physical activity remain essential.”

Building a case for VR as an emerging tool, the article’s author and Obesity Care Clinic’s CEO, Dr Stéphane Bach, writes:

VR has already shown potential in various healthcare applications, including surgical training and mental health interventions. In obesity behavioral therapy, VR offers a unique opportunity to create immersive experiences that facilitate behavior change and support weight loss efforts. By leveraging exposure therapy, realistic visualization, and gamification, VR-based interventions can help individuals develop healthier eating habits and overcome challenges associated with traditional therapy methods.

According to Dr. Bach, VR has been making significant strides in healthcare for several decades. The concept dates back to the 1990s when researchers began exploring its potential in areas like surgical training and phobia treatment. Since then, advancements in VR technology have led to more sophisticated and immersive systems, expanding the range of healthcare applications. Today, VR is used in various medical fields, from medical education and patient rehabilitation to mental health interventions and pain management.

The advantages VR can offer include:

  • Creating realistic, immersive simulations that closely mimic real-world scenarios
  • Enabling personalized, engaging, and interactive interventions
  • Enhancing patient adherence and motivation
  • Ability to access it remotely, a convenient and cost-effective alternative to traditional in-person treatments.

Potential uses might be:

Exposure Therapy for Food Cravings: VR can expose individuals to virtual representations of their trigger foods, teaching coping strategies to reduce the intensity and frequency of food cravings. This approach is similar to exposure therapy used in treating anxiety disorders and phobias.

Realistic Portion Size Visualization: VR can provide realistic visualizations of portion sizes, helping individuals understand and adhere to appropriate serving sizes, thus preventing overeating.

Gamification of Healthy Eating Habits: VR can gamify healthy eating habits, incorporating points, rewards, and challenges to motivate healthier food choices and commitment to weight loss goals.

Of course, to fully realize the potential of VR in obesity behavioral therapy, challenges related to technical limitations, cost and accessibility, integration with existing treatment programs, and the need for long-term efficacy studies must be addressed. We’ll stay tuned.

Finally, a reminder: The ability to rechannel displacement into less harmless activities rather than succumbing to urges is behind the behavior modification app, BrainWeighve, currently ramping up for a trial through the University of California Los Angeles (UCLA). The trial focuses on weight loss for obese teens using “a self-directed, physician-supervised program withdrawing from one problem food at a time.”

Your responses and feedback are welcome!

Source: “The efficacy of internet-based cognitive behavioral therapy for adult binge spectrum eating disorders: A meta-analysis,” ScienceDirect (Journal of Affective Disorders), 9/15/24
Source: “Virtual Reality as a Frontier in Obesity Behavioural Therapy: Immersive Diet Control,” Obesity Care Clinic, 6/21/24
Source: “Cognitive Behavioral Therapy for Eating Disorders,” ResearchGate/PubMed, September 2010.
Image by Mitch on Unsplash

Are Crucial Questions Being Addressed?

As of last month, the people who keep close track of these matters, namely, have identified more than 80 pharmaceutical firms that currently have more than 100 new anti-obesity drugs in the “pipeline,” the wide area that exists in between the gleam of inspiration and the marketing of a finished product. Naturally, the public expects that a medicine offered for sale has jumped through every possible hoop, and is as safe to use as human ingenuity can make it.

There are so many types of products, based on so many different molecules, with several possible routes of administration, and each one of them is in a different stage of development or testing. The test parameters will depend on whether the route of administration is oral, subcutaneous, parenteral, intravenous, topical, or other. And what about its type? Recombinant fusion proteins, small molecule, monoclonal antibody, peptide, polymer, or other?

There is clinical assessment, and then there is of course commercial assessment. What are the product’s “growth prospects”? This means, in business-speak, how soon can we get this product on the market and how much can we sell it for, and how much can we make off it every year going forward? And can our product become the top dog, the one undeniable and universally acknowledged winner that leaves all other contenders in the dust?

Between discovery and permission for unfettered sales, a hopeful drug faces many stages of trial and possible rejection. Concerning all of these 100+ hopeful entries in the anti-obesity sweepstakes, answers are anxiously awaited by financial officers of the companies, stockholders, the medical establishment, and the public.

And then, there’s this

What many people fail to understand, or choose to ignore, about the majority of products with strongly established market shares — products that have already been accepted, and that are used by millions of people — is that a distressing number of significant questions about them are equally unanswered. How can this be? As it turns out, it is because those questions have not been asked. The title of an article by Jonel Aleccia is a simple declarative sentence: “Drugs aren’t required to be tested in people who are obese.”

In the USA, somewhere around 40% of adults are filed in the obese category. And yet, an astonishing number of the familiar medications, both prescription and over-the-counter, have not been tested on officially obese human bodies. The writer states:

That’s because they are not required to be included in drug studies. And often, they’re explicitly excluded.

Many widely prescribed drugs and over-the-counter medications work differently in people who are obese, but exactly how and at what dose often isn’t clear.

At a workshop last year, FDA Commissioner Dr. Robert Califf acknowledged a “deficit of evidence” about how medicines act in patients who are obese. The NIH now encourages researchers to consider the impact of excluding obese people in their studies…

Aleccia cites work done by drug researcher Christina Chow, who recently reviewed over 200 new drug studies, of which almost two-thirds did not document the subjects’ weight or BMI. Apparently, most drugs of every kind that have ever made it to the market were tested primarily on Caucasian adult males. Sure, we don’t want the health or lives of vulnerable populations to be put in danger. Any kind of testing on children, expectant mothers, or anyone whose health is already compromised needs to be conducted with the utmost care.

But fat people get the flu too, and experience pain, and become accidentally pregnant, and suffer every malady that remedies have been devised for. Considering how many of them there are, medicines that work for them are definitely needed, along with definitive information on how to calculate the effective dose considering their body weight. Chow explains the dangers of not weight-relating certain specific drugs, including one that treats schizophrenia, the emergency conception prevention drug, and even ibuprofen:

Some drugs can become concentrated in fat tissues and not in the bloodstream. That means there will be less medication in the blood, leading to undertreatment… Other drugs remain in the body longer in the obese. That could result in harmful drug interactions if another medication is added too soon.

One group needs to be figured out quickly, considering its ever-growing number of members. More and more elderly people just hang in there and refuse to become extinct. How are scientists expected to use them as test subjects? But how can they not? And every day the senior citizen count increases, including a goodly number of obese senior citizens.

Your responses and feedback are welcome!

Source: “Obesity Pipeline Research 2024,”, 06/26/24
Source: “Drugs aren’t required to be tested in people who are obese,”, 11/07/23
Image by Aaaarrrrgggghhhh!/Attribution 2.0 Generic

GLP-1 Drugs and Celebrities

In the old days, meaning the late 60s and early 70s, adherents of the fat acceptance movement could be found at public protests, throwing diet books and pictures of Twiggy into bonfires, as if they were draft cards. Nowadays, writer Shane O’Neill suggests, the National Association to Advance Fat Acceptance has mellowed into a group that aspires to influence legislation and end discrimination. Other people with similar feelings have gravitated to the more ambitious and militant Body Positivity movement.

For instance, when activist Virgie Tovar received partnership offers from various weight-loss companies, she notified her Instagram followers, “I don’t want Ozempic.” Tovar is not alone in that sentiment. Many people feel that too many body-positive and fat-positive influencers have transmogrified into advocates for weight loss. Their followers feel betrayed. The reporter describes the internet talk show, “It’s Bigger Than Me” produced by pharmaceutical giant Novo Nordisk.

Of course, the drug company has a justification:

We are not here to denounce body positivity or detract in any way from the strides we, as a community, have made in inclusivity. The reality is that two truths exist — obesity can impact health, but the discrimination, stigma and shame experienced by people living with obesity for their weight is also very real.

Meanwhile, if there is one thing the average American loves more than weight loss, that other thing is celebrity worship. A shocking number of average folk want — nay, demand — to know which famous people are using the trendy GLP-1 drugs, for how long, and why, or why not. And how many pounds they have lost, and how often they throw up, or stay home because they are afraid they will throw up.

It has also been open season on celebrities who say the wrong thing about other celebrities’ weight-loss drug use, whether they express criticism or approbation — and out there in the zeitgeist, there is no shortage of either.

Men are more rarely heard from

In the spring of last year, Mark Wahlberg put his feelings on the record. The actor is known for his strict fitness regime which includes rising at 2:30 AM for the first of several daily workout sessions. Wahlberg, of course, is not a normal person, having gained and lost large amounts of weight for film roles. He does it all with exercise and correct eating, saying, “You’d be surprised what you can accomplish when you’re willing to do the work.” He does not judge others harshly, but would definitely prefer them to choose the “good old-fashioned way.”

In the recent past, has contacted show biz professionals and recorded their Ozempic experiences. Sharon Osbourne reported taking an unnamed weight-loss drug for four months, feeling nauseated through most of it, and losing 30 pounds. Then in September, she appeared on a talk show and confessed, “I didn’t want to go this thin” — which, apparently, was under 100 pounds.

Actor and “internet personality” Samantha Jo took Mounjaro, and described how peaceful her inner life had become since the “food noise” quieted down, and she understood for the first time what it was like to be a normal person not constantly besieged by thoughts of eating. Jo also told the public that all the positive attention she had attracted was not always comfortable, although her audience had increased and more advertisers sought her out.

There were resentful thoughts, like, “I wasn’t good enough for you then. And the only thing that has changed about me now is my weight… I don’t see how your weight should indicate how you’re treated or if you’re worthy of respect.”

Writer and editor Samhita Mukhopadhyay stopped using Mounjaro because of the expense but also has philosophical objections. Namely, prying into the lives of celebrities as if we had the right, is just a “weird witch hunt, and all these discussions only prove how determined humans are to invent “more tools to judge each other with.”

Your responses and feedback are welcome!

Source: “New marketing push by Ozempic and others sparks body-positive backlash,”, 02/14/24
Source: “Mark Wahlberg Is Not A Fan Of The Ozempic Weight Loss Fad,”, 05/04/23
Source: “Stars Who Have Admitted,”, 09/22/23
Source: “Rocker’s Famous Wife,”, 05/08/23
Source: “Food is one of life’s great pleasures. Will weight-loss drugs end that?,”, 10/02/23
Source: “‘You look great! Ozempic?’ The new minefields of weight-loss etiquette,”, 06/25/24
Image by Hollywood Branded/ATTRIBUTION 2.0 GENERIC

Behavioral Therapy, Not Weight-Loss Drugs, Experts Say

The US Preventive Services Task Force (USPSTF) updated its recommendations in June for how primary care clinicians can effectively assist children with high body mass index (BMI), a standard metric used to identify obesity. The task force emphasized that extensive and intensive behavioral interventions are the most effective means for helping children achieve a healthy weight.

Although recent studies have highlighted the success of weight-loss drugs and surgical procedures for children, and the American Academy of Pediatrics endorses these methods as viable options, they are not included in the USPSTF’s current recommendations. The task force’s call for a significant number of hours dedicated to behavioral interventions has frustrated some healthcare providers, who find these guidelines unrealistic or problematic.

Recommendations overview

The latest recommendations from the USPSTF — a volunteer panel of independent medical experts —advise clinicians to offer intensive behavioral interventions to children aged six and older with a high BMI or to refer them to such services.

BMI for children is calculated differently than for adults, though both use height and weight to estimate mass. For adults, a BMI of 30 or higher indicates obesity, whereas for children, a high BMI is defined as being at or above the 95th percentile for their age and sex. This means a child’s BMI is higher than 95% of peers of the same age and gender, according to CDC growth charts. Parents can use the CDC’s online calculator to estimate their child’s body fat percentage.

The USPSTF’s recommended interventions include self-monitoring, goal-setting, supervised physical activity, instruction in healthier eating, and limits on screen time. These interventions should be tailored to fit the patient and their family and should involve at least 26 hours per year, including supervised physical activity.

Research reviewed by the USPSTF indicates that children in intensive programs typically experience modest weight loss and BMI reduction within six months to a year. Greater success was noted in those who spent more time with clinicians and included physical activity in their regimen.

Significance of the recommendations

High BMI in children can lead to severe and potentially life-threatening health issues, such as diabetes, respiratory problems, bone and joint issues, liver conditions, skin problems, high blood pressure, and high cholesterol, which can lead to heart disease. Obesity also exposes children to bullying, affecting their emotional well-being and self-esteem.

Approximately 20% of US children have a high BMI, with obesity rates tripling over the past four decades. The USPSTF recommendations guide primary care providers on effective preventive care, influencing insurance coverage decisions. Under the Affordable Care Act, preventive services graded A or B by the task force must be covered by private insurers; the new child obesity recommendations received a B grade.

Practical challenges

Dr. Susma Vaidya, a pediatrician running a weight loss clinic at Children’s National Hospital in Washington, acknowledges the importance of intensive behavioral intervention but views the 26-hour annual recommendation as impractical. She said:

“We lack the infrastructure to provide such intensive therapy,” noting the challenges for providers, parents, and children in committing to this time frame, which may only yield minimal BMI improvements.

Dr. Mona Sharifi, an associate professor at Yale School of Medicine, who contributed to the American Academy of Pediatrics guidelines on managing childhood obesity, appreciates the emphasis on behavioral treatments. However, she notes that little progress has been made since the 2010 and 2017 recommendations, and access to these treatments remains poor, possibly worsened by the pandemic.

Lack of surgical recommendations

Some doctors also criticize the USPSTF’s decision not to include surgical options. Despite the American Academy of Pediatrics considering bariatric surgery a viable option, the task force did not review the latest research, viewing surgery as outside the primary care scope.

Medication recommendations

The USPSTF also refrained from recommending weight-loss drugs, citing insufficient evidence. While studies on medications like liraglutide, semaglutide, orlistat, phentermine, and topiramate showed larger BMI reductions compared to placebos, long-term effects and potential harms remain unclear, according to task force member Dr. John Ruiz.

Dr. Vaidya argues that these FDA-approved medications have transformed her practice, helping children who struggled with lifestyle interventions alone. “The role of pharmacotherapy cannot be understated,” she said, noting that these drugs can facilitate adherence to lifestyle modifications.

And pharma companies agree

Companies producing popular weight loss injections like Ozempic and Mounjaro are beginning to test versions for children as young as six years old who struggle with obesity.

Eli Lilly announced its intention to start clinical trials with Mounjaro for children aged 6-11. Novo Nordisk, the maker of Ozempic, reported it is in phase three of testing Saxenda, a version of its drug for children aged 6-12.

However, experts stress that lifestyle and behavior modifications should be the primary focus of treatment. The weight loss injections can cost up to $1,500 and may not be covered by insurance. The studies are expected to span several years.

Your responses and feedback are welcome!

Source: “To help children with high BMI, expert panel recommends 26 hours of behavior coaching — but not weight-loss drugs,” CNN, 6/18/24
Source: “Ozempic, Mounjaro manufacturers testing weight loss drugs for kids,” MSN, undated
Image by Food Photographer | Jennifer Pallian on Unsplash

More Interesting Things About GLP-1 Receptor Agonists

For, Deborah Hinnen wrote, “Proper patient selection and education can assist in achieving positive treatment outcomes.” The writer is talking about the utility of the GLP-1 drugs in treating diabetes, but the same can be said of their use to fight obesity. Patient selection implies that some people, even if they could greatly benefit from any particular treatment, are just not suited to it for other reasons.

Education is paramount in any case. We hope that the patient will take any words that come directly from the physician’s mouth as gospel, and strive to obey “doctor’s orders” to the best of their understanding and ability.

But during office visits, patients are often not at their psychological best. They are worried about how to rearrange their lives to accommodate the new demands made upon them and their families. They are concerned about expenses, and thinking ahead to the possibility that today’s prescription might not help at all, and there will be rough times in store.

Sometimes they have what we used to quaintly call a “mental block” against absorbing certain items of information. An adult patient will sometimes bring along a friend to pay attention and take notes. For a minor individual, of course, there is a good chance that a parent will be present — which is not guaranteed to be a solution, as the attention span and comprehension depth of a parent or guardian can never be taken for granted, either.


In an office setting, no matter what the doctor says or forgets to say, in the best-case scenario other staff members will make every effort to assure that the instructions and warnings are understood. They will ask if the patient has any questions, or needs clarification about anything. They might hand out a printed information sheet, or directions to a helpful online resource. Of course, even then, there is no guarantee that the helpful information will be pursued or assimilated.

The “I” word

Of more immediate interest is a recent report with the word “injury” in its title: “Acute Kidney and Liver Injury Associated With Low-Dose Liraglutide in an Obese Adolescent Patient.” This paper originates with four members of the Faculty of Medicine at the Hebrew University of Jerusalem. The complete work is accessible for a fee.

The brief summary version begins by recalling that liraglutide was approved in 2020 for people aged 12 through 18, as an adjunctive therapy for weight management “in combination with a reduced-calorie diet and increased physical activity.” It goes on to say,

Although reports in adults have suggested a link between liraglutide and adverse effects including hepatic injury and acute kidney injury (AKI), these effects have not previously been reported among adolescents treated with liraglutide for weight loss.

The cause for alarm was the experience of a 17-year-old boy afflicted with class III obesity, which is the more recent enlightened term for what used to be called morbid obesity. He had been using liraglutide (at its lowest recommended dose) for three months, and consequently experienced not only significant appetite loss, and weight loss, but a sensation of melancholy. By the standard of the Adverse Drug Reaction Probability Scale, it seemed clear that the liraglutide was also responsible for the injury to his liver and kidneys.

After being off the medication for a month, his kidney issue had settled down and his liver enzymes had reverted to normal, and there was an improvement in his mood. The authors note,

Our report highlights the importance of vigilance in monitoring for these potential adverse effects among adolescents treated for obesity with any dose of liraglutide.

Liraglutide had been approved in 2010 as antidiabetic therapy for adults. A document from that year states that some rodent study results were troubling, but there was no firm evidence of adverse effects on humans. Reports of several different conditions, like pancreatitis, appeared here and there, but in very small numbers, and the evidence to connect the cases with the drug was just not there.

Your responses and feedback are welcome!

Source: “Glucagon-Like Peptide 1 Receptor Agonists for Type 2 Diabetes,”, 2017
Source: “Acute Kidney and Liver Injury Associated With Low-Dose Liraglutide in an Obese Adolescent Patient,”, 06/12/24
Source: “Weighing Risks and Benefits of Liraglutide — The FDA’s Review of a New Antidiabetic Therapy,”, 03/04/10
Image by the healthy blog/Public Domain

Unlocking the Potential of GLP-1 Agonists Beyond Diabetes and Weight Loss

Initially developed for diabetes treatment, GLP-1 agonists have gained significant attention for their weight-loss benefits. The success of GLP-1 medications like Ozempic, Wegovy, Mounjaro, and Zepbound has spurred a wave of research exploring their potential beyond diabetes and weight loss.

Discovering secondary uses for GLP-1s

The headlines are coming at us fast and hard. Just in recent weeks, we’ve read that the GLP-1 agonists may help reduce sleep apnea, reduce pancreatitis risk in obese and diabetic patients, reduce rheumatoid arthritis symptoms, and potentially even boost fertility.

In other words, these medications are changing consumer habits and industry dynamics, and people just can’t get enough of them. While the pharmaceutical industry is eagerly investigating new applications for GLP-1 drugs, some think that the real opportunity lies in precision medicine. This approach promises to open numerous commercial pathways and significantly advance personalized patient care.

Why precision medicine?

Elliott Green, the co-founder and CEO of Dandelion Health, which collects and processes clinical data for the healthcare industry, is one of the believers. In a recent article he penned for Fast Company, he opined that, as the COVID-19 pandemic taught us, rapid innovation is crucial for saving and improving lives on a large scale. However, traditional clinical trials, while scientifically rigorous, are not designed for speed and cost-effectiveness.

In Green’s opinion, the challenge is accelerating precision medicine for GLP-1 drugs by applying lessons from the pandemic to achieve near-term, data-driven insights that lead to personalized treatments and care.

Learning from oncology

It’s complicated though. Green writes:

To understand just how “blackbox” GLP-1 drugs are today, one only needs to read or listen to the news. For example, early GLP-1 studies seem to appear daily, and they point to potential issues, such as unwanted side effects in some patients, like psychiatric issues, or opportunities — like GLP-1 agonists potentially being used to treat prostate cancer one day. The key word here? Potential.

With increasing access to data and advancements in AI, healthcare providers should be able to predict which patients will benefit most from specific weight loss drugs. Similarly, pharmaceutical companies should be able to identify new, effective uses for GLP-1 formulations. While progress is being made, it is not happening quickly enough to optimize patient outcomes or confirm new applications for these drugs.

Adopting a proactive approach from oncology, where precision medicine has had a significant impact, could be transformative. Oncologists select treatments based on the genetic profile of tumors. Similarly, GLP-1 drugs could be chosen based on a digital phenotype that predicts the best response with minimal side effects.

Addressing data gaps

The challenge in bringing precision medicine to GLP-1 drugs lies in the lack of real-world data. Although there is more real-world data (RWD) than ever before, much of it remains isolated and unreadable, locked in various systems within healthcare organizations.

RWD often comes from electronic health records (EHR), claims data, and disease-specific registries. However, the most valuable data — unstructured clinical data like waveforms (e.g., ECGs) and imaging data (e.g., MRIs, CT scans) — is typically outside the EHR. This data, which constitutes over 80% of healthcare data, holds immense potential for personalizing GLP-1 care and accelerating drug development. 

Leveraging AI for precision medicine

In Green’s words,

[W]e can take these broad generalizations and turn them into more precise hypotheses to be tested, like: demonstrating GLP-1’s therapeutic effects beyond current uses, including secondary benefits derived from exploratory use or demonstrated with additional data modalities; and developing precision-medicine tools to identify patients with uncontrolled symptoms or to match patients to the right treatment plans.

The bottom line

To advance personalized weight loss treatments, there must be stronger integration of both structured and unstructured health data, and a robust approach to vetting AI algorithms trained on rich, unbiased datasets. This will provide the necessary insights for personalized patient care and help pharmaceutical companies quickly and cost-effectively explore new uses for GLP-1 drugs.

By embracing these strategies, we can drive a more personalized approach to weight loss and unlock new therapeutic potentials for GLP-1 drugs, benefiting patients and the healthcare industry alike.

Your responses and feedback are welcome!

Source: “How AI can power GLP-1’s next frontier in medicine,” Fast Company, 6/7/24
Source: “Ozempic and Wegovy May Help Reduce Rheumatoid Arthritis Symptoms,” Healthline, 6/27/24
Image by lightfieldstudios/123RF

Interesting Things About GLP-1 Receptor Agonists

Most of the research on these drugs, over the years, has been performed with an eye to their usefulness in treating Type 2 diabetes. The findings are also, obviously, pertinent to their effects when prescribed for weight loss in non-diabetic patients.

And of course, it is not their effects alone that matter, but what happens when those effects combine with whatever else the patient is already taking? The professional with a prescription pad must be meticulously conscientious in recording a patient’s history, lest something important and potentially threatening slip through the net.

Regarding the currently existing GLP-1 RA meds, there are a few widely recognized contraindications. Except for oral semaglutide, the others are administered by subcutaneous injection. Some concerns do or may apply to all drugs in this class; others are so far known to only be relevant to one of them. Fortunately, many of the potential problems mainly apply to conditions that are relatively quite rare.

A very detailed report originated in 2006 and has been revised 11 times since then, now stating (among other things):

All GLP-1 agonists have been found to cause c-cell tumors in rodent models, but the human relevance has not been determined. All agents except for [two] have a black box warning for risk of thyroid C-cell tumors,

GLP-1 agonists have not been studied in patients with gastroparesis, and all drugs within this class, except for liraglutide and semaglutide, recommend against use in patients with preexisting gastroparesis.

However, their rep is mostly positive:

There is no basis for limiting the duration of treatment for GLP-1 agonists in patients using this medication for chronic weight management if it remains beneficial for weight loss and is not causing intolerable side effects.

Here are some of the caveats and cautions applicable to either the whole class, or various individual drugs. All of them are, of course, contraindicated in patients who are hypersensitive to the particular substance. All should be warned that since the drugs increase the sensation of satiety, it is quite possible that continuing to eat past the point of feeling full can cause nausea and/or vomiting.

Individual drugs are warned against for patients with existing or incipient pancreatitis, gastroparesis or inflammatory bowel disorders, renal disease, or Multiple Endocrine Neoplasia syndrome type 2. Likewise, for those who have a family history of medullary thyroid cancer.

They probably should be avoided for patients who are on tricyclic antidepressants. It should be noted that the GLP-1 receptor agonists, which are therapeutic peptides, could potentially cause the development of drug antibodies.

Another article, titled “Glucagon-like Peptide-1 (GLP-1) Receptor Agonists,” offers a very thorough comparison of the various available meds of this type. For starters, their efficacy and safety “primarily differ by their frequency of administration.” They all delay gastric emptying and increase satiety, and “There is no significant [clinically meaningful] difference in weight loss effect among the agents in the class.”

Here are other details that could be very disappointing, because none of these things match up with what their various manufacturers would have us believe:

Semaglutide is the only GLP-1 receptor agonist that is available as a once-daily oral tablet. Unlike semaglutide injection, the evidence of CV benefit using the oral route has not been definitively established. Compared to placebo, all agents, except albiglutide, significantly reduced weight and increased the risk of hypoglycemia and GI side effects. There were no clinically meaningful differences in weight loss effects, blood pressure reduction, or hypoglycemia risk among the drugs.

Your responses and feedback are welcome!

Source: “Drug Use Criteria: Glucagon-Like Peptide 1 Receptor Agonists,”, October 2022
Source: “Compare and Contrast the Glucagon-Like Peptide-1 Receptor Agonists (GLP1RAs),”, 03/27/23
Source: “Glucagon-like Peptide-1 (GLP-1) Receptor Agonists,”, 04/11/22
Image by Consumerist Dot Com/ATTRIBUTION 2.0 GENERIC

More Vagus Nerve Knowledge

The previous post listed some activities of the vagus nerve as having to do with…

[…] stomach expansion, stomach contraction, gastric acid release, stomach content release into the small intestine, digestive pancreatic enzyme secretion and the sensations of both hunger and fullness.

Who is in charge of those departments? Who tells the vagus nerve what messages to convey? It now appears that the directives carried from this area of the body originate with the gut microbiome (as differentiated from, for instance, the skin microbiome).

The notion does seem rather radical, and it feels appropriate to resist the idea that just about everything we are, and do, is fundamentally determined by our colonies of gut bugs. Although we may diligently seek help from various treatment modalities, it is very likely that, where mood and behavior are concerned, the little critters are running the show.

Not surprisingly, the same cluster of functions performed by and related to the stomach, is heavily influenced by bariatric surgery, which causes a faction of professionals to wonder: Rather than subject children to the ordeal of surgery, if the same benefits can be achieved by somehow controlling the vagus nerve, why not concentrate on that? How can it be done?

The vagus nerve has been compared to an “information superhighway” that conveys messages from the gut to the brain. It seems that if we could influence the microbiota in regard to the messages they dispatch through the vagus nerve, that might help. It has even been suggested that “probiotic bacteria could be tailored to treat specific psychological diseases.”

This sounds like a great idea when the potential benefit for autistic children, for one example, is considered. They tend to become obese, because that is a side effect of the only drugs that are approved to treat their condition. This is also true of the drugs used against anxiety, epilepsy, and depression. If the body could be induced to manufacture its own meds to deal with those conditions, the results would be pretty spectacular… and apparently, thanks to the efforts of its microscopic tenants, it can.

The gut-brain axis is a thing

For, Carla Delgado described how ultra-processed foods can cause inflammation in the gut, as well as in other parts of the body, and how the inflammation connects with mental symptoms of anxiety and depression. This information comes from Dr. Uma Naidoo of Massachusetts General Hospital, who is credentialed as not only a psychiatrist and nutrition specialist but also a professional chef.

Nutritional Psychiatry does not insist that correlation equals causation — however, the evidence against ultra-processed foods is quite damning. By all indications, the brain is tightly bound to the gut microbiome because of the vagus nerve connection, which is compared again to a “fast two-way highway sending signals and chemicals back and forth.” Dr. Naidoo is quoted:

We produce over 90 percent of our body’s serotonin — as well as other neurotransmitters which govern mood — outside the brain, in the gut where our food is digested and broken down into vitamins, minerals and other nutrients. This enables a natural symbiosis between food and the body’s brain chemistry.

Do emotional and mental disorders cause overeating? Obviously. Does overeating cause mental and emotional disorders? Undoubtedly. And right there in the middle of everything, facilitating the two-way communication, is the vagus nerve.

Your responses and feedback are welcome!

Source: “How Ultra-Processed Foods Can Affect Your Mental Health,”, 10/24/22
Image by NIH Image Gallery/ATTRIBUTION 2.0 GENERIC

GLP-1 Drug Makers Go After Counterfeit Versions

In breaking news last week, Eli Lilly is preparing to sue several medical spas and wellness centers for allegedly selling counterfeit and compounded versions of its popular weight loss and diabetes drugs, Mounjaro and Zepbound. This issue has also been raised by Novo Nordisk, the maker of Ozempic, and health organizations, who warn that these fake products can cause serious side effects, including infections.

In an open letter on Thursday, Eli Lilly cautioned against using drugs labeled “research purposes only” or “not for human consumption,” highlighting that federal regulators have not approved oral versions of Mounjaro or Zepbound, despite some pills appearing online.

The counterfeit drugs are said to be unsafe

The company claims that some wellness centers and websites are selling unauthorized versions of these drugs made with unapproved chemicals and marketed as generic versions, even though Lilly does not produce generic versions of its drugs. These counterfeit products are dangerous because they may contain incorrect dosages, wrong medications, no medication, or a mix of several medications, posing serious health risks.

According to Lilly, fake tirzepatide — the active ingredient in Mounjaro and Zepbound — has been found to contain bacteria, high levels of impurities, and different chemicals than genuine drugs. These fake products often have safety, efficacy, and sterility issues.

The FDA does NOT approve

Counterfeiting is not limited to tirzepatide. In December, the FDA warned against using counterfeit semaglutide, the active ingredient in Ozempic and Wegovy, due to potential adverse events such as infections and abdominal pain. Since 2020, the FDA has received over 100 adverse event reports related to counterfeit tirzepatide and semaglutide, including several life-threatening cases, 19 hospitalizations, and at least two deaths.

How to spot a fake

To identify fake GLP-1 drugs, Lilly advised looking for a pink hue in the product (genuine versions are colorless), generic labeling (neither Lilly nor Novo Nordisk sells generic versions), incorrect dosages, grammatical errors on the packaging, lack of tamper-resistant features, and mismatched batch numbers.

The reason for the fakes is to meet the demand

The National Association of Boards of Pharmacy has noted that high demand and short supply of these drugs have led to the sale of substandard and falsified versions, putting patients at risk. Both Wegovy and Ozempic, as well as Zepbound and Mounjaro, have experienced shortages due to high demand. Lilly warned that fake versions of its products are also being sold online and on social media, where it does not sell genuine Mounjaro or Zepbound.

Current steps being taken by the drug makers

In its letter, Lilly also announced legal action against medspas, wellness centers, and clinics selling unapproved and counterfeit versions of its drugs. The company claims these clinics falsely market the fake products as Mounjaro and Zepbound, misuse Lilly’s clinical trial results, and deceptively use the FDA’s approval of genuine drugs to sell the counterfeits.

Lilly has previously filed similar lawsuits and settled with one company, Totality Medispa, which agreed to comply with federal law and report all adverse events to the FDA. Novo Nordisk has also filed lawsuits against nine wellness clinics for selling compounded versions of Ozempic and Wegovy, some of which contained up to 24% impure chemicals. Novo Nordisk is seeking to stop these companies from marketing and selling products claiming to contain semaglutide and is asking for compensation of up to $75,000.

Your responses and feedback are welcome!

Source: “WHO warns about fake versions of weight loss drugs Wegovy and Zepbound,” NBC News, 6/20/24
Source: “Weight-Loss Drugs Dangers Explained: Zepbound, Mounjaro Maker Warn Of Coming Counterfeit Lawsuit,” Forbes, 6/20/24
Image by sosiukin/123RF

FAQs and Media Requests: Click here…

Profiles: Kids Struggling with Weight

Profiles: Kids Struggling with Obesity top bottom

The Book

OVERWEIGHT: What Kids Say explores the obesity problem from the often-overlooked perspective of children struggling with being overweight.

About Dr. Robert A. Pretlow

Dr. Robert A. Pretlow is a pediatrician and childhood obesity specialist. He has been researching and spreading awareness on the childhood obesity epidemic in the US for more than a decade.
You can contact Dr. Pretlow at:


Dr. Pretlow’s invited presentation at the American Society of Animal Science 2020 Conference
What’s Causing Obesity in Companion Animals and What Can We Do About It

Dr. Pretlow’s invited presentation at the World Obesity Federation 2019 Conference:
Food/Eating Addiction and the Displacement Mechanism

Dr. Pretlow’s Multi-Center Clinical Trial Kick-off Speech 2018:
Obesity: Tackling the Root Cause

Dr. Pretlow’s 2017 Workshop on
Treatment of Obesity Using the Addiction Model

Dr. Pretlow’s invited presentation for
TEC and UNC 2016

Dr. Pretlow’s invited presentation at the 2015 Obesity Summit in London, UK.

Dr. Pretlow’s invited keynote at the 2014 European Childhood Obesity Group Congress in Salzburg, Austria.

Dr. Pretlow’s presentation at the 2013 European Congress on Obesity in Liverpool, UK.

Dr. Pretlow’s presentation at the 2011 International Conference on Childhood Obesity in Lisbon, Portugal.

Dr. Pretlow’s presentation at the 2010 Uniting Against Childhood Obesity Conference in Houston, TX.

Food & Health Resources