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

Why Is the Most Recommended Childhood Obesity Treatment Not Readily Available?

For many U.S. parents seeking help for a child with obesity, the most widely endorsed treatment is out of reach — and it’s not the popular GLP-1 agonists like Wegovy, used for weight loss and managing diabetes.

What is the recommended childhood obesity treatment?

Leading medical groups recommend intensive behavioral counseling, spanning 26 hours within one year, to teach children and their families practical ways to eat healthier and be more active. Sounds good, right? A recent Reuters article digs into the reasons these touted programs aren’t easy to find.

And why is not widely available?

These programs are not widely accessible, with wait lists often stretching for several months. They are frequently not covered by health insurance and require a time commitment that many families find challenging, according to interviews with over a dozen doctors and parents.

No treatment option improvement is expected

Consequently, fewer than 1% of the nearly 15 million U.S. children with obesity receive this type of structured care, the U.S. Centers for Disease Control and Prevention (CDC) told Reuters. Efforts by the CDC and other organizations to expand insurance coverage have stalled, doctors involved in the process also told Reuters.

“The coverage for these programs was never good, and we’re not seeing any movement toward improvement,” said Dr. Joseph Skelton, a professor of pediatrics and obesity medicine specialist at Wake Forest University School of Medicine.

No end in sight for curbing childhood obesity

The prevalence of obesity among U.S. children has steadily increased, from 5% in 1980 to nearly 20% now, according to the CDC. It’s also a global issue. New research published by JAMA Pediatrics and based on a review of global studies revealed that the prevalence of obesity increased by 150% in the period covering 2012–2023 compared to 2000–2011, indicating that pediatric obesity and overweight conditions are increasingly common. The problem is getting worse.

This is where the GLP-1 drugs come in

According to new research, the number of young people in the US prescribed GLP-1 agonist drugs, such as Wegovy and Ozempic, for weight loss and diabetes increased by 594.4% over the past three years. The most notable increase in prescriptions was observed among young women and adolescent girls.

Last year, the American Academy of Pediatrics updated its obesity management guidelines, recommending that in addition to behavior and lifestyle interventions for the entire family, weight loss medications are suitable for children aged 12 and older.

Clinical trials involving intensive behavioral programs for children and found that, on average, children lost 5.7 pounds. In contrast, Wegovy and similar drugs have resulted in a more dramatic weight loss — 15% or more of body weight in clinical trials. This significant weight loss, coupled with a lack of insurance coverage for counseling, may lead more families to consider these medications in the future.

Are GLP-1 medications safe for children?

In short, more research is needed. Many doctors and parents are cautious about using the medication due to the lack of data on its potential impact on a child’s development and other long-term risks.

Some doctors argue that increased use of Wegovy among youth will make it even more critical for children to learn healthy eating habits for the long term. They are concerned that relying solely on the drugs could lead to nutritional deficiencies or eating disorders.

Dr. Thomas Robinson, a professor of pediatrics and director of the Center for Healthy Weight at Stanford Medicine Children’s Health in Palo Alto, California, said:

Many of us believe it would make sense to offer behavioral counseling along with the drug. These drugs are very effective at reducing weight and health risks, but you don’t all of a sudden adopt a healthy diet or become more physically active.

Your responses and feedback are welcome!

Source: “Weight-loss options for children are hard to come by,” Reuters, 6/17/24
Source: “Prescriptions for weight loss, diabetes drugs for young people leaped 600% since 2020, study says,” CNN, 5/23/24
Image by Omar Lopez on Unsplash

Can Web-Based Self-Help Interventions Help With BED?

A recent JAMA Network Open study assessed the effectiveness of web-based self-help interventions in alleviating binge eating disorder (BED). Here are some details, including the findings and the conclusions.

Why BED?

We’ve covered it many times before, but let’s recall that BED is defined as uncontrolled overeating that can lead to obesity, type 2 diabetes, and hypertension. Prolonged BED can reduce the affected person’s quality of life, negatively impact social relationships, and compromise their ability to perform their job well. Without a timely intervention, BED can become chronic and even lead to premature death.

CBT and its barriers

Some studies have demonstrated that cognitive behavioral therapy (CBT) can serve as an effective BED intervention, as well as positively affect the eating disorders bulimia nervosa and anorexia nervosa.

Unfortunately, some people with BED don’t seek in-person psychotherapy because of such barriers as treatment costs, lack of availability, and sociocultural stigma.

This is where web-based cognitive behavioral interventions come in, thanks to their ease of implementation, availability, reduced social stigma, and cost-effectiveness. This avenue has been growing in popularity for these reasons, making BED treatment more accessible.

About the study

The study involved a randomized clinical trial (RCT) to evaluate the effectiveness of a web-based cognitive behavioral self-help intervention for BED. Researchers measured changes in eating disorder symptoms, well-being, co-morbid psychopathology, self-esteem, emotion regulation, and clinical impairment. Weekly symptom monitoring and ecological momentary assessment (EMA) were used to track real-time changes in binge eating.

Participants were recruited from Germany and other German-speaking regions in Europe. Eligible participants were 18-65 years old, owned a smartphone, and were diagnosed with BED according to the DSM-5 criteria. They were randomly assigned to either a control group (waiting list) or a web-based treatment group. Assessments were conducted at baseline, six weeks (mid-treatment), and 12 weeks (post-treatment).

The intervention consisted of six mandatory modules covering psychoeducation, self-monitoring of binge eating, emotion regulation, and interactive exercises. A sequential module-access strategy was employed to engage participants in a personalized manner.

Study findings

The study found significant changes in BED patterns from baseline to 12 weeks in the intervention group. Out of 1,602 patients, 154 met the eligibility criteria and were recruited, with 77 participants in each group. The intervention group reported fewer binge-eating episodes and showed significant improvements in global eating psychopathology and clinical impairment.

Dr. Priyom Bose, Ph.D., discussing the study results, writes:

“The intervention’s efficacy exceeded or was similar to previously documented digital interventions, as well as in-person guided and unguided self-help interventions for BED.

Notably, the levels of improvement observed in the intervention group were consistent with or surpassed those associated with in-person CBT interventions, thus confirming the clinical applicability of web-based cognitive behavioral self-help interventions.”

The study noted that participants’ motivation, attitudes towards online interventions, demographic characteristics, and treatment expectations influenced the positive effects of the web-based intervention.

The bottom line

The study demonstrates that web-based cognitive behavioral self-help interventions can significantly improve the well-being of people with BED, offering a promising alternative to traditional treatments. However, the study had some limitations, including the under-representation of males and older adults, and potential biases due to the self-report design. Future research can address these limitations through methodologies like double-blind designs.

Your responses and feedback are welcome!

Source: “Web-based self-help program proves effective in treating binge eating disorder,” News-Medical.net, 5/19/24
Source: “Effectiveness of a Web-Based Cognitive Behavioral Self-Help Intervention for Binge Eating Disorder,” JAMA Network Open, 5/16/24
Image by Glenn Carstens-Peters on Unsplash

Will the Cheaper Weight Loss Regimens Replace GLP-1 Drugs?

When patients start on the latest obesity drugs, they often experience reduced food cravings and significant weight loss. However, discontinuing these drugs usually reverses these effects: cravings return, and so does the weight. For instance, within a year of stopping semaglutide — known as Wegovy or Ozempic — people typically regain about two-thirds of the weight they lost. Tirzepatide, marketed as Zepbound or Mounjaro, shows similar patterns. This has led to the medical consensus that these obesity drugs need to be taken indefinitely, perhaps for life.

For pharmaceutical companies selling these blockbuster drugs, collectively known as GLP-1 drugs after the hormone they mimic, this is a lucrative prospect. For patients, who might be paying over $1,000 a month out of pocket, it’s a different story. Most Americans simply can’t afford such ongoing expenses, as a recent article in The Atlantic outlines.

Finding cheaper alternatives

This financial burden has prompted some doctors to get creative, developing regimens that substitute cheaper, though less well-known, alternatives. GLP-1 drugs are highly effective, promoting more rapid weight loss than any other obesity medications currently available.

However, some doctors are exploring whether these drugs need to be used permanently. “What if we use them short-term, for six months to a year, to lose 50 pounds?” asks Sarah Ro, an obesity-medicine doctor and director of the University of North Carolina Physicians Network Weight Management Program. She and other doctors are investigating transitioning patients to older, less expensive drugs for long-term maintenance.

Dr. Ro has already helped hundreds of patients make this switch out of necessity. Many of her patients in rural North Carolina lack insurance coverage for the new obesity drugs and can’t afford them out of pocket. When North Carolina’s state employee health insurance cut off coverage for GLP-1 drugs in April, Ro transitioned her patients to older medications like topiramate, phentermine, metformin, and bupropion/naltrexone, coupled with lifestyle counseling. These alternatives are generally less effective, leading to about half the weight loss of GLP-1 drugs, but are far more affordable, costing as little as $10 a month when prescribed as generics.

Retirees on Medicare lose GLP-1 drug coverage

Jamy Ard, an obesity medicine doctor at Wake Forest University School of Medicine, also had to adjust his approach for patients who lost GLP-1 drug coverage upon retiring and switching to Medicare, which currently does not cover obesity treatments. Doctors like Ard see the need for research on transitioning from GLP-1 drugs to older ones, as many patients will lose coverage at retirement age. “Now I’ve got to figure out, well, how do I treat them?” he said.

Are the alternatives safe?

Long-term data on older drugs are sparse, largely because obesity drugs weren’t profitable enough to justify expensive, long-term studies until recently. Switching from GLP-1 drugs to older medications is largely anecdotal at this point, with varying outcomes. A small minority can maintain their weight with just diet and exercise, while others find the older drugs ineffective. Dr. Ro’s experience suggests that 50% to 60% of her patients have successfully maintained weight loss using older drugs alongside lifestyle changes like cutting out fast food and sugary drinks.

A tailored trial-and-error approach is the way to go

The choice of alternative medication depends on the patient. Different drugs target different biological pathways. For example, the combination of naltrexone and bupropion reduces the pleasure of eating and is particularly effective for emotional eaters. Topiramate makes carbonated drinks unpleasant, which can help soda drinkers. Each drug has different side effects, requiring a tailored approach and sometimes trial and error to find the best fit.

Doctors are also finding that some patients can maintain their weight on lower or less frequent doses of GLP-1 drugs. Lowering the dose doesn’t save money since the pens cost the same regardless of dosage, but extending the time between doses can help stretch supplies.

Stopping completely might be a challenge

Complete discontinuation of obesity medications, GLP-1 or otherwise, is unlikely for most patients. Weight loss triggers compensatory mechanisms in the body, evolved to prevent starvation, making long-term maintenance a constant challenge. Susan Yanovski, co-director of the NIH’s Office of Obesity Research, describes long-term weight maintenance as the “holy grail” of obesity treatment.

The best maintenance strategy — whether it involves GLP-1 drugs, and at what dose — remains an individual question needing further study. “These are really good research questions,” Yanovski said, though they might not align with the pharmaceutical companies’ focus on developing new drugs.

Compounded semaglutide is announced

Hims & Hers company announced last week that it will be selling compounded semaglutide for weight loss at prices significantly lower than Wegovy and Ozempic, addressing a gap in supply. However, it’s important to note that compounded semaglutide is not FDA-approved and undergoes less extensive testing than brand-name drugs.

This compounded GLP-1 drug will be prescribed by physicians through their telehealth platform. Prices start at $79 per month for oral medication kits and $199 per month for injections, much lower than the list prices of Ozempic ($935.77) and Wegovy ($1,349.02).

However, compounded semaglutide differs from FDA-approved drugs like Wegovy and Ozempic in several key ways. Compounded medications do not undergo the rigorous FDA approval process, which ensures safety, efficacy, and quality through extensive testing. This lack of testing can lead to concerns about inconsistent potency, bioavailability, and safety.

Also, these drugs can vary in how they are absorbed and utilized by the body, potentially leading to unpredictable therapeutic outcomes. Safety concerns also arise from the sterility and cleanliness of the compounding process, which might introduce harmful contaminants if not properly managed.

The BrainWeighve app would be an ideal off ramp…

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: “Ozempic Patients Need an Off-Ramp,” The Atlantic, 5/22/24
Source: “Hims & Hers Selling GLP-1 Weight Loss Drugs Like Wegovy for 85% Less: What to Know,” Healthline.com, 5/22/24
Image by Thought Catalog on Unsplash

Study Finds That Severe Childhood Obesity Can Cut Life Expectancy in Half

Severe childhood obesity can drastically reduce life expectancy, cutting it nearly in half, according to a recent global study conducted by Stradoo GmbH, a life sciences consultancy in Munich. This research provides detailed insights into how the age of onset, severity, and duration of childhood obesity affect long-term health and life expectancy.

Long-term impact of childhood obesity

Presented at the European Congress on Obesity (ECO) in Venice, Italy, the study findings quantified the impact of various aspects of childhood obesity on long-term health for the first time. It was led by Dr. Urs Wiedemann along with colleagues from universities and hospitals across Europe and the United States.

The researchers found that the earlier a child develops obesity, the more severe the long-term effects. For instance, a child living with severe obesity at age four, who does not lose weight, has a life expectancy of just 39 years — about half the average life expectancy.

The findings in detail

“While it’s widely accepted that childhood obesity increases the risk of cardiovascular disease and related conditions such as type 2 diabetes (T2D), and that it can reduce life expectancy, evidence on the size of the impact has been patchy,” said Dr. Wiedemann. She added:

A better understanding of the precise magnitude of the long-term consequences and the factors that drive them could help inform prevention policies and approaches to treatment, as well as improve health and lengthen life.

The researchers developed an early-onset obesity model to estimate the effect of childhood obesity on cardiovascular disease, related conditions like T2D, and life expectancy. This model included four key variables: age of obesity onset, obesity duration, irreversible risk accumulation (a measure of irreversible health effects even after weight loss), and severity of obesity.

Critical factors

The severity of childhood obesity was measured using BMI Z-scores, which indicate how much an individual’s Body Mass Index (BMI) deviates from the norm for their age and sex. For example, a four-year-old boy with a BMI Z-score of 3.5, indicating severe obesity, has a life expectancy of just 39 years if he does not lose weight.

Data for the model were drawn from 50 existing clinical studies on obesity and related comorbidities, involving over 10 million participants worldwide. Approximately 2.7 million of these individuals were between two and 29 years of age.

The risks of severe childhood obesity

The model shows that earlier onset and more severe childhood obesity elevate the likelihood of developing related health issues later in life. For instance, a child with a BMI Z-score of 3.5 at age four has a 27% likelihood of developing type 2 diabetes by age 25 and a 45% chance by age 35. In contrast, a child with a BMI Z-score of 2 at age four has a 6.5% chance of developing type 2 diabetes by age 25 and 22% by age 35.

Higher BMI Z-scores at an early age also lead to a lower life expectancy. For instance, a BMI Z-score of 2 at age four without subsequent weight reduction reduces life expectancy from about 80 years to 65 years. The life expectancy drops further to 50 years for a BMI Z-score of 2.5 and 39 years for a BMI Z-score of 3.5.

Implications for early weight loss

Comparisons with other studies and expert opinions confirmed the model’s accuracy. Moreover, the model demonstrated the positive impact of weight loss on life expectancy and long-term health. For example, a child with severe early onset obesity (BMI Z-score of 4 at age four) has a life expectancy of 37 years and a 55% risk of developing T2D by age 35. If the child loses weight, reducing the BMI Z-score to 2 by age six, life expectancy increases to 64 years, and the risk of T2D drops to 29 percent.

“The early onset obesity model shows that weight reduction has a striking effect on life expectancy and comorbidity risk, especially when weight is lost early in life,” said Dr. Wiedemann.

Addressing childhood obesity

The model has some limitations. It does not account for the causes of obesity, genetic risk factors, ethnic or sex differences, or the interactions between different comorbidities. However, the impact of childhood obesity on life expectancy is profound.

Dr. Wiedemann said:

It is clear that childhood obesity should be considered a life-threatening disease. It is vital that treatment isn’t put off until the development of type 2 diabetes, high blood pressure, or other ‘warning signs’ but starts early. Early diagnosis should and can improve quality and length of life.

The bottom line

The findings of this study underscore the urgent need for early intervention in cases of childhood obesity. Preventative measures and timely treatments are crucial to improving the long-term health and life expectancy of affected children. As our understanding of the long-term consequences of childhood obesity deepens, so too must our commitment to tackling this critical public health issue from an early age.

Your responses and feedback are welcome!

Source: “Severe childhood obesity can cut life expectancy in half,” Earth.com, 05/16/24
Source: “Young children with persistent severe obesity could have half average life expectancy, study finds,” The Guardian, 05/14/24
Image by Christopher Williams on Unsplash

New Research Highlights Importance of Sugar Source in Childhood Obesity

New research presented at the European Congress on Obesity (ECO) in Venice, Italy, has shed light on a critical aspect of childhood nutrition: the source of sugar. The study, conducted by Junyang Zou and colleagues from the University of Groningen and University Medical Center Groningen, challenges conventional wisdom regarding sugar consumption and its relationship to childhood obesity.

The type of sugar might matter more than the amount

The study, which examined data from the GEKCO Drenthe study, a longitudinal investigation tracking children born in the northern Netherlands, scrutinized the impact of sugar consumption from various sources on weight gain and the development of obesity. Surprisingly, the research suggests that the type of sugar consumed may be more influential than the total amount.

Contrary to common assumptions, the study found that the overall quantity of sugar consumed during early childhood did not correlate with weight status at age 10 or 11. However, the source of sugar emerged as a significant factor.

Zou elaborated:

The high consumption of sugary foods is considered a risk factor for childhood overweight and obesity and so children are advised to consume less sugar-rich foods, such as confectionery, cakes and sugar-sweetened drinks, and eat more fruit and unsweetened dairy products, such as milk and yogurt.

But while fruit and unsweetened dairy products are considered healthy, they contain high amounts of intrinsic sugars — sugar that occurs naturally in the food, rather than being added. We wanted to know if the source of sugar, added versus intrinsic, as well as the amount, affects the likelihood of developing overweight or obesity.

The research underscores the importance of distinguishing between intrinsic sugars and added sugars found in processed treats and beverages. While both fruit and unsweetened dairy products contain intrinsic sugars, they also offer essential nutrients and may confer protective effects against obesity.

Study results in more detail

Drawing upon data from the GECKO Drenthe study — an extensive longitudinal investigation tracking children born between 2006 and 2007 in the northern Netherlands — Zou and colleagues meticulously analyzed the dietary habits of 817 children who maintained a healthy weight at age 3. The findings yielded compelling insights into the diverse sources of sugar and their distinct effects on weight status.

On average, these children consumed 112 grams of sugar daily, comprising a blend of natural and added sugars. Among the primary sources identified were sugar-sweetened beverages, dairy products, sugary snacks, and fruits. Surprisingly, while total sugar intake at age 3 did not exhibit a significant correlation with BMI at ages 10 and 11, the source of sugar emerged as a critical determinant of weight status.

Notably, children who derived a higher proportion of their sugar intake from whole fruits demonstrated lower BMI scores and experienced less weight gain as they approached adolescence. Similarly, those who consumed more sugars from unsweetened liquid dairy products, such as milk, exhibited a reduced risk of developing obesity or overweight status.

Conversely, sugar intake from sugary snacks was associated with higher BMI scores, underscoring the detrimental impact of added sugars found in processed foods. Despite the study’s observational nature, the findings offer valuable insights into the nuanced relationship between sugar consumption and childhood obesity.

The bottom line

The research presented at the ECO highlights the critical role of sugar sources in the development of obesity during childhood. It also underscores the imperative of reevaluating dietary recommendations to prioritize nutrient-rich sources of sugar, such as fruits and unsweetened dairy products, while minimizing the consumption of sugary snacks and beverages. By empowering parents, healthcare professionals, and policymakers with evidence-based insights, we can chart a course toward a healthier future for our children — one sweet choice at a time.

Your responses and feedback are welcome!

Source: “Understanding the role of sugar sources in development of childhood obesity,” News-Medical.net, 05/13/24
Source: “Kids’ Obesity Risk Depends on Source of Sugar, Not the Amount,” Newsweek, 05/13/24
Image by Myriam Zilles on Unsplash