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

Fooling the Body With Filler

While bariatric surgery makes the stomach smaller, so less food will fit inside, a patient dedicated to non-compliance can definitely stretch that pouch back out again. Another method seeks to reduce the space available for food, not by tailoring the stomach itself into a smaller receptacle, but instead by filling it with non-food.

This work was done at Peking University First Hospital in Beijing, China:

Oral intragastric expandable capsules taken twice daily before meals reduce body weight in adults with overweight or obesity…

The tactic can cause “mild gastrointestinal adverse events,” but it has the advantage of being a non-invasive, non-permanent intervention. Another desirable feature is a lack of the many side effects that pharmacological methods too often trigger. Oral and intragastric, the capsule enters the mouth and lands in the stomach where it “expands to fill about one quarter of average stomach volume and then passes through the body.”

In the Chinese study, it took 24 weeks (six months, or half a year) for study participants to lose as little as 5% of baseline body weight, which seems paltry compared to some other methodologies.

Much more remains to be discovered about this way of doing things, because of the limitations of this small study in which only fewer than 4% of the subjects had type 2 diabetes. Also, they are characterized as “relatively young,” so they did not experience metabolic or cardiovascular effects that might kick in later. Here is an interesting detail:

Gastrointestinal disorders were reported in 25.0% of participants in the intragastric expandable capsule group compared with 21.9% in the placebo group, with most being transient and mild in severity.

To put it another way, a quarter of the participants taking the real stuff experienced unpleasant side effects — and so did almost as many of the subjects taking imaginary medicine. When people ingest something that is totally inert and inactive, and yet are visited by adverse results, that is the nocebo effect. “A nocebo effect can occur if a person takes a real or active medicine, and can also occur if they are given a placebo.”

Both placebo and nocebo effects are fascinating areas in which a whole lot of additional investigation is obviously needed. There is a lot going on in this realm, including controversy over the ethics. One article says,

Unfortunately, guidance for informing trial participants about trial intervention harms, in a way that is ethical, understandable, and does not produce nocebo effects, is currently under-researched. A recent study suggested that information provided to trial participants often fails to tell them what they wish to know, and that it is presented in a way that is difficult to understand.

What is this stuff, anyway?

Intragastric expandable capsules consist of two naturally derived components, food-grade carboxymethylcellulose cross-linked with citric acid, forming a three-dimensional polymer matrix that rapidly absorbs water and occupies the volume of the stomach and small intestine when administered orally with water before a meal, subsequently producing satiety. Each capsule contains no less than 10 000 highly absorbent cellulose-based hydrogel particles…

Dietary fiber comes in two varieties: soluble and insoluble. Soluble dietary fiber has long been recommended for its stomach-filling effect. It has been found to slow gastric emptying, increase perceived satiety, and significantly aid in appetite regulation. But its usefulness appears to depend on such variables as molecular size and solubility, and food matrix.

In addition, “Viscous soluble dietary fibres are believed to be more capable of inducing satiety compared to non-viscous soluble dietary fibres.” So apparently, “soluble fibres are not all created equal.” One vital area for additional research is the possibility that combinations of soluble fibers might be even more effective than any single type.

Your responses and feedback are welcome!

Source: “Premeal Stomach-Filling Capsule Effective for Weight Loss,” MDedge.com, 02/13/24
Source: “Placebo effect,” Vic.gov.au, undated
Source: “Harmful placebos,” Ox.ac.uk, 12/11/18
Source: “Efficacy and safety of intragastric expandable oral capsules in adults with overweight or obesity,” Doi.org 01/22/24
Source: “Unravelling the Effects of Soluble Dietary Fibre Supplementation on Energy Intake and Perceived Satiety in Healthy Adults,” NIH.gov, 01/06/19
Image by Edward Russell/CC BY 2.0 DEED

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

Semaglutide and Psychiatric Risk

Weight gain and its associated health risks often pose significant challenges for people with psychiatric disorders. The intersection of mental health and physical well-being necessitates careful consideration of treatment options, particularly when addressing weight management.

Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, gained FDA approval in 2017 for the treatment of type 2 diabetes. It operates by mimicking the GLP-1 hormone, which regulates insulin production and influences food intake and reward mechanisms within the brain. The medication, renowned for its efficacy in weight loss, has recently come under scrutiny for its potential psychiatric side effects, prompting clinicians and patients to reevaluate its role in managing obesity, particularly in people living with serious mental illness.

The APA poster on psychiatric comorbidities

Heidi Anne Duerr, MPH, reported for Psychiatric Times on a case study that was presented at the 2024 American Psychiatric Association Annual Meeting. The study shed light on the complexities of using semaglutide in patients with psychiatric comorbidities.

Presented in the poster titled “Semaglutide-Induced Suicidal Ideation in a Patient with Psychiatric Comorbidities: A Case Report,” study author Raju Kakarlapudi and colleagues recounted the upsetting experience of a 42-year-old female patient dealing with morbid obesity and type 2 diabetes mellitus alongside bipolar I disorder and posttraumatic stress disorder (PTSD).

The patient’s difficult journey

Bariatric surgery, a common weight loss intervention, was deemed unsuitable due to the patient’s psychiatric history. Consequently, semaglutide, marketed as Ozempic, emerged as a viable alternative to help the patient manage weight. However, within a mere three weeks of starting the medication, the patient started exhibiting “significant psychiatric disturbances including abrupt behavioral alterations and protracted nihilistic delusions.” Disturbingly, she even attempted self-strangulation on multiple occasions. Subsequent discontinuation of semaglutide led to the disappearance of these behavioral changes.

Additional research uncovered this

Kakarlapudi and colleagues said that…

The primary aim [was] to augment awareness regarding the potential adverse effects associated with Ozempic utilization, both among the general populace and within the psychiatric community.

Kakarlapudi et al. conducted an extensive literature review using Google Scholar, uncovering approximately 60 documented cases of suicidal ideation and seven suicide attempts linked to semaglutide use. Interestingly, many patients reported an improvement in depression upon discontinuation of the drug, suggesting a potential association between semaglutide and depressive symptoms that could precipitate suicidal ideation.

What we were told back in January

Interestingly, it was widely reported last January that health agencies in the U.S. and Europe have conducted thorough reviews and found no evidence linking thoughts of suicide or self-harm to semaglutide. The European Medicines Agency concluded after a nine-month review that there is no causal association between GLP-1 receptor agonists and suicidal thoughts or actions. Similarly, the Food and Drug Administration (FDA) in the U.S. reached a similar conclusion after examining reports to its adverse event reporting system. That only goes to show that more research is needed while we proceed with caution when it comes to using these weight loss medications.

The bottom line

The authors of the case study underscored the need for further research to elucidate the underlying mechanisms by which semaglutide may exacerbate psychiatric symptoms and precipitate suicidal ideation. By identifying specific proteins and enzymes implicated in these adverse effects, clinicians can better mitigate risks and tailor treatment strategies to individual patient needs.

Your responses and feedback are welcome!

Source: “Annual Meeting: Poster Investigates the Link Between Semaglutide and Suicidal Ideation,” Psychiatric Times, 05/07/24
Source: “Ozempic isn’t linked to suicidal thoughts, U.S. and European health agencies find,” NBC News, 4/15/24
Image by Hans Reniers on Unsplash