Recent Evaluations of Pediatric Obesity Treatments

As we know, obesity now affects over 20% of children in the United States, and while there are proven interventions to address it, many children still lack access to these treatments. Yale researchers recently explored the cost-effectiveness of one such intervention and examined the challenges and successes in implementing another. Their goal was to identify ways to increase access to effective pediatric obesity treatments. The studies were published in the journal Obesity.

Why do we need these studies?

These studies come at a crucial time. Experts from Yale, in collaboration with national medical organizations, are backing a proposal being considered by the Centers for Medicare and Medicaid Services. This proposal suggests a new billing code that could allow health insurance to cover intensive behavioral and lifestyle treatments for childhood obesity. Such a change would encourage the adoption of these programs and improve access, according to the researchers.

Previous research has shown that interventions providing comprehensive, family-focused nutrition and behavioral education with at least 26 contact hours over a three- to 12-month period are effective in treating childhood obesity. These programs have been recommended by the U.S. Preventative Service Task Force and the American Academy of Pediatrics.

Dr. Mona Sharifi, one of the study authors and an associate professor of pediatrics at Yale School of Medicine, said:

We have effective treatment options… But there are systemic barriers that limit access, and we need to address them urgently.

The first study findings

Cost is a recurring issue in healthcare programs, including obesity treatments. In the first study, Sharifi and her colleagues evaluated the costs associated with implementing the Healthy Weight Clinic intervention in federally qualified health centers from both healthcare and societal perspectives.

The Healthy Weight Clinic offers intensive behavioral and lifestyle treatment for children and adolescents with obesity or overweight. The program involves a team of pediatricians, dieticians and community health workers delivering care within primary care settings, where families are already engaged. The researchers focused on federally qualified health centers because they serve underserved communities disproportionately affected by obesity.

“This choice was intentional to reach communities that face higher obesity disparities,” Dr. Sharifi explained.

The researchers broke down the costs of the intervention, including personnel, materials, and family expenses like time, transportation, and childcare. They then used a model to simulate the impact on a sample of patients over 10 years, comparing those who participated in the Healthy Weight Clinic with those who did not.

The findings showed that if Healthy Weight Clinics were available in all federally qualified health centers over 10 years, they could reach 888,000 children with obesity or overweight and prevent 12,100 cases of obesity and 7,080 cases of severe obesity. The cost per child was estimated at $667, with $456 covered by the healthcare sector and $211 incurred by families. The reduction in obesity cases could save an estimated $14.6 million in healthcare costs over the same period.

Dr. Sharifi said:

It’s a relatively low-cost intervention that our team previously found to be effective… And scaling it up in federally qualified health centers could help reduce health disparities in underserved populations.

The second study findings

In the second study, the researchers examined another intervention by looking at the spread of a program called Smart Moves, which is based on Yale’s Bright Bodies program. Earlier research by Drs. Sharifi, Mary Savoye (the creator of Smart Moves), and others found Bright Bodies to be effective in improving health outcomes in children with obesity and overweight and more cost-effective than standard clinical care.

Between 2003 and 2018, the Smart Moves curriculum was introduced in over 30 sites across the U.S. The new study collected feedback from staff at those sites to identify what helped or hindered the program’s success.

Addressing funding instability

Local partnerships with schools and exercise facilities were key to successfully implementing Smart Moves by providing resources and creating demand for the program. However, funding instability was a major barrier, often preventing programs from being implemented or sustained.

According to Dr. Sharifi,

When a child breaks their arm, their family seeks care, and the clinic bills the insurance company. But this funding model doesn’t work as well for behavioral and lifestyle treatment programs. For example, Bright Bodies involves group visits with families and is led by a dietician, an exercise physiologist, and a social worker.

But insurance companies typically don’t reimburse these programs, even though Bright Bodies has proven to be more effective and cost-saving than usual care. Programs often rely on grants, which eventually run out, leaving communities without access to standard care.

To address this, several organizations, including the American Academy of Pediatrics, the American Academy of Family Physicians, and the CDC, have submitted a proposal for a new billing code. The Centers for Medicare and Medicaid Services will review this proposal in the coming months.

“If approved, it would open the door to more efficient funding for these treatments and give families better access to interventions,” Sharifi said. “In other areas like surgery, not reimbursing for standard care would be unheard of, but in pediatrics, children often get overlooked in health policy, and pediatricians are underpaid.”

Policy changes are needed to ensure that first-line treatments are available to families across the country, Sharifi emphasized.

“Expanding access to these treatments is a pressing need,” she said. “Denying equitable access to effective, low-cost treatment for children is simply unethical.”

What else could be done?

According to the World Economic Forum (and proven by research and statistics), policymakers are working to address harmful food marketing, particularly by restricting marketing to children, imposing taxes on sugary drinks, mandating clear nutrition labels, and limiting portion sizes.

Additionally, research indicates that digital health interventions, such as text messaging programs and digital therapeutics, show promise in supporting weight management and promoting healthy behaviors among children and adolescents.

Your responses and feedback are welcome!

Source: “Evaluating the benefits of and barriers to pediatric obesity programs,” Medical Xpress, 8/28/24
Source: “Childhood obesity — how do we tackle this worsening health issue?,” World Economic Forum, 8/30/24
Image by Vitolda Klein on Unsplash

Is the Natural Compound Berberine a Safer Alternative to Weight Loss Medications?

As we’ve been seeing over and over, a new class of medications, GLP-1 agonists — including Ozempic, Wegovy and Mounjaro — has gained immense popularity since their release. These medications work by mimicking hormones that influence the body’s control over appetite and food intake, as well as slowing digestion to promote a sense of fullness. Common side effects include gastrointestinal issues and injection site reactions.

These drugs have been a breakthrough for those dealing with weight-related conditions such as diabetes, high blood pressure, and heart disease. However, as with any new medication hailed as a “miracle” solution, some people use them to shed a few pounds for aesthetic reasons.

Susan B. Trachman, M.D., in her article in Psychology Today, writes that she is particularly concerned about how these “miracle” drugs might impact mental health. She reminds us that previously, weight-loss drugs like Zimulti were pulled from the European market due to increased reports of suicidal thoughts and behaviors. In the U.S., Qnexa (Vivus), containing phentermine and topiramate, was rejected by the FDA due to concerns over potential risks, including suicidal ideation, despite demonstrating significant weight loss.

Alarming side effects of GLP-1 drugs

While the research on the subject remains limited and conflicting, suicidal ideation has been linked to other weight-loss drugs in the past. For example, Sanofi’s Acomplia, which was never approved in the U.S., was withdrawn from the European market in 2008 due to similar concerns. Contrave, another weight-loss drug, carries a “black box warning” for suicidal thinking, and Qsymia includes a warning advising users to stop taking it if they experience such thoughts.

A recent study, published in the journal JAMA Network Open, examined reports of suicidal thoughts among individuals using semaglutide, whether for diabetes management or weight loss. The researchers analyzed data from a World Health Organization database that tracks adverse drug reactions in over 140 countries.

Out of more than 30,500 people taking semaglutide, 107 reported experiencing suicidal thoughts. Similarly, 162 cases of suicidal ideation were found among over 52,000 patients using liraglutide, another injectable diabetes medication from the same drug class as semaglutide. Since liraglutide has been on the market longer, it has been used by more people.

The study highlighted a disproportionate risk of suicidal thoughts in individuals taking semaglutide, which was not observed in those on liraglutide. Comparing the frequency of suicidal thoughts in semaglutide users with those on other medications in the database, the researchers noted an approximately 45% higher risk associated with semaglutide use.

Enter berberine, nature’s potentially safer alternative

Given that even a slight risk of suicidal ideation should be carefully monitored and mitigated, nature offers a potentially safer alternative for weight loss: berberine. This compound is found in various plants, including goldenseal, barberry, and Oregon grape, and has been used for centuries in Ayurvedic and Chinese medicine. Traditionally, berberine has been utilized to treat infections, skin diseases, and digestive issues. More recently, it has gained attention for its potential positive effects on diabetes and heart disease, as well as its growing popularity as a weight-loss aid.

When taken as a pill or powder, berberine enters the bloodstream and interacts with cells, influencing various biological processes. Instead of targeting a single pathway, berberine acts on multiple fronts, impacting several conditions simultaneously.

In a review published in Biomedicine and Pharmacotherapy, researchers highlighted berberine’s effectiveness in lowering fasting blood sugar levels in hundreds of patients. Additionally, the compound was found to reduce body mass index in a small group of subjects over three months. Other studies have shown that berberine supplements can reduce cardiovascular risk in postmenopausal women by lowering total cholesterol, and when combined with blood pressure medication, it has enhanced the effects of the treatment in hypertensive patients.

Berberine seems to decrease insulin resistance, which can lead to obesity and type 2 diabetes. It may also modulate gut hormones that regulate food intake and energy balance. However, scientific studies focused specifically on berberine’s weight-loss effects are limited due to small sample sizes. One such study involving individuals with fatty liver disease found that those who took berberine daily for three months experienced significant weight loss.

Berberine improves cellular responses to insulin and affects how blood sugar is utilized, helping reduce hunger signals. Additionally, it benefits gut health by promoting a balanced gut microbiome, suppressing harmful bacteria, and encouraging the growth of beneficial ones.

Thinking about trying berberine?

If you consider adding berberine to your regimen, Dr. Trachman advises:

The FDA does not regulate it. Try to source a higher-quality product to avoid side effects from additives in some less expensive forms.

Berberine does interact with some drugs because it can inhibit the clearance of these drugs from the liver, causing an elevated blood level. Check with your healthcare provider before starting this if you take prescription medication.

Berberine’s half-life is only a few hours. That means your blood level will decrease to about 50 percent within a few hours. To maintain a more constant level, many providers recommend multiple daily dosing — two or three times per day at a total of 1500mg.

On a final note, side effects, primarily gastrointestinal, include constipation, nausea, and diarrhea — similar to the side effects reported with newer weight-loss drugs. However, unlike those drugs, berberine has not been associated with mental health issues.

Your responses and feedback are welcome!

Source: “Is Berberine Nature’s Weight Loss Drug?, Psychology Today, 8/23/24
Source: “A study linking popular weight loss drug to suicide risk again raises long-standing safety questions,” CNN.com, 8/20/24
Image by Chris Abney on Unsplash

New Obesity Treatments Show Promise

A research team led by Dr. Ki-young Shin at the Human Care Electro-Medical Device Research Center, part of the Electro-Medical Equipment Research Division at KERI, is making significant progress in developing neuromodulation technology to treat and manage metabolic syndrome.

Metabolic syndrome is a cluster of conditions, including obesity, high blood pressure, and elevated triglycerides, often linked to poor diet and lack of exercise. While various treatments for obesity exist, such as drug injections and pharmaceuticals, these chemical approaches often carry the risk of side effects with long-term use. In response, Dr. Shin’s team at KERI has introduced a new method that involves suppressing appetite by electrically stimulating the cerebral cortex through the scalp.

This technique, known as transcranial random noise stimulation (tRNS), has shown promise in non-invasively targeting the dorsolateral prefrontal cortex to reduce appetite. The research team has identified three key technologies essential for this approach: accurately delivering electrical stimulation to the desired brain area, developing electrodes that can effectively contact the scalp through hair, and creating monitoring systems to ensure the stimulation reaches the target and alters brain activity. Dr. Shin’s team is actively developing these advanced technologies.

To validate the effectiveness of tRNS in suppressing appetite, KERI collaborated with Professor Hyung-jin Choi’s team at Seoul National University Hospital in a clinical trial. This trial involved 60 female participants, divided into two groups — one receiving tRNS and the other an active sham treatment. Over two weeks, each participant underwent six sessions of electrical stimulation, with 20-minute sessions using a barely noticeable 2 mA current. The aim was to demonstrate the potential of tRNS in reducing appetite.

Arrowhead to start two new obesity trials

After wrapping up its work on a cardiovascular candidate in the clinical stage, Arrowhead Pharmaceuticals is now turning its focus to two new obesity treatments, both slated to begin clinical trials in early 2025.

The company introduced two next-generation candidates: ARO-INHBE and ARO-ALK7. These are designed to address obesity and related metabolic disorders.

In preclinical studies, both candidates demonstrated the ability to reduce body weight and fat mass through a novel mechanism of action that could help preserve lean muscle mass, offering a potential advantage over current therapies. Arrowhead plans to seek regulatory approval to start human trials for both candidates by the end of this year, aiming to initiate clinical studies in obesity early next year.

As Dr. Carel le Roux, a metabolic medicine expert from University College Dublin, noted during the investor call:

Weight loss alone isn’t a sufficient value proposition for continuing medication. You need to see health and functional improvements as well.

According to Arrowhead’s chief of discovery and translational medicine, Dr. James Hamilton, when tested as monotherapy and in combination with tirzepatide in diet-induced obesity mouse models, ARO-INHBE and ARO-ALK7 both led to reduced body weight and fat mass while preserving lean muscle mass, resulting in improved body composition. Dr. Hamilton added that with the recent approval and positive clinical impact of new obesity treatments, emerging therapeutic strategies with novel mechanisms of action could represent the future of effective obesity and metabolic disease management.

Your responses and feedback are welcome!

Source: “KERI advances neuromodulation technology for appetite suppression in obesity treatment,” News-Medical.net, 8/14/24
Source: “After clearing out heart disease drug, Arrowhead maps out obesity development plans,” FierceBiotech.com, 8/14/24
Image by CDC on Unsplash

GLP-1 Drugs Are Coming in Pill Form

Most of us are aware of injectable GLP-1 drugs for type 2 diabetes and obesity, like Ozempic and Wegovy. However, did you know there are also pill versions of these drugs, with more potentially on the way?

Rybelsus is an oral form of semaglutide, a GLP-1 drug used to treat type 2 diabetes alongside diet and exercise. It is produced by Novo Nordisk, the same company behind Ozempic and Wegovy.

Approved by the FDA for type 2 diabetes since 2019, Novo Nordisk is exploring whether a higher dose of oral semaglutide can be as effective as the weekly injectable Wegovy for weight loss. Eli Lilly is also developing an oral GLP-1 called orforglipron to treat obesity or overweight in adults. Eli Lilly’s phase 2 results show orforglipron, a daily oral nonpeptide GLP-1 receptor agonist, achieved up to a 14.7% mean weight reduction at 36 weeks in adults with obesity or overweight.

Pfizer is entering the oral GLP-1 market with an experimental pill called danuglipron for adults with obesity, intended for daily use rather than the weekly injectables. “Obesity is a key therapeutic area for Pfizer, and the company has a robust pipeline of three clinical and several pre-clinical candidates,” said Mikael Dolsten, M.D., the chief scientific officer and president of research and development at Pfizer.

But will oral GLP-1s change the game and appeal to those turned off by injectables? According to experts, it depends.

Britta Reierson, M.D., a metabolic health and primary care physician and the medical director of Knownwell, said:

I don’t think we’re going to shift away [from injectables] because that wave of interest is already happening… but there needs to be oral options as well… There needs to be a broadened toolkit available because we know that this treatment isn’t one-size-fits-all across the board.

How oral GLP-1s could impact treatment

Oral GLP-1 drugs could improve drug access, especially if refrigeration is an issue, noted Marc-Andre Cornier, M.D., the director of the division of endocrinology, diabetes, and metabolic diseases at the Medical University of South Carolina and president-elect of The Obesity Society. Injectable GLP-1s like Ozempic or Wegovy require proper storage at low temperatures, which can be challenging in certain parts of the world. An oral version could circumvent this issue.

Dr. Reierson added that oral GLP-1s could help address the drug shortage issues common with injectables, as they are generally easier to manufacture. “We need to focus more time and energy on developing GLP-1s in an oral form to make this treatment more sustainable, because there is a crisis in supply and demand with the injectables,” she said.

Aside from supply issues, some people might be deterred by needles or have safety concerns about injections. An oral version of semaglutide could alleviate these worries.

However, Dr. Cornier pointed out that many people who find injectables effective do not mind the needle format and might prefer a weekly injection over a daily pill. For some, a weekly injection could be more convenient than daily medication.

Rybelsus, for instance, must be taken on an empty stomach with no more than 4 ounces of water. Users need to wait 30 minutes before eating, drinking, or taking other oral medications. In contrast, Ozempic can be taken anytime, with or without food.

Cost and side effects remain major factors

Even if the needle is removed, side effects still exist for oral medications. If someone cannot handle the side effects of an injectable GLP-1, an oral pill likely will not solve the problem. “The GI side effects, nausea, vomiting, and constipation…those seem to be across the board. The higher the dosage of the oral medication, the more likely those side effects are,” Dr. Reierson said.

Affordability is also a significant concern. Unless oral medications are significantly cheaper than injectables, access will remain an issue for those needing GLP-1 drugs. Currently, the out-of-pocket costs for Rybelsus are almost the same as for Ozempic.

It makes sense that the drugmakers are rushing to flood the market with currently popular drugs and pave the way for research on new versions in different forms and potency.

Doug Baker, VP of industry relations for The Food Industry Association, said, “In the next few years, we could see anywhere from 12 to 36 million people that could be potentially on this”, noting that FMI has knowledge of 70 different trials in the works at the Food and Drug Administration for new GLP-1 drugs. Also, data gathered from 5,577 U.S. adults in early March for a Gallup poll revealed that 6% of U.S. adults have tried GLP-1 drugs for weight loss, and 3% are currently using them.

Your responses and feedback are welcome!

Source: “Would You Be More Likely to Take GLP-1s If They Came in Pill Form?,” VeryWellHealth.com, 8/6/24
Source: “Nearly a third of U.S. consumers could begin using GLP-1 drugs,” SupermarketNews.com, 8/5/24
Source: “Bernstein poll: 6% of US adults have already tried GLP-1’s for weight loss,” Investing.com, 8/5/24
Image by Kateryna Hliznitsova on Unsplash