Experts Continue Evaluating Benefits and Risks of GLP-1 Agonists

As we know, over the past 30 years, rates of overweight and obesity in the U.S. have more than doubled, creating a growing public health crisis. Projections suggest that by 2050, 213 million adults and 43 million children will face overweight or obesity. Researchers have been emphasizing that urgent action is needed to address this issue.

A recent Medscape article looks into one promising intervention that involves glucagon-like peptide-1 receptor agonists (GLP-1 RAs), initially developed for diabetes and now approved for weight loss. These drugs have seen a dramatic rise in popularity, with prescriptions increasing by 132.6% from late 2022 to late 2024. Public awareness has also surged, with 32% of surveyed U.S. adults reporting familiarity with GLP-1 RAs in 2024, compared to just 19% in 2023.

GLP-1 RAs and their effectiveness

GLP-1 RAs, including tirzepatide (which targets additional receptors beyond GLP-1), have demonstrated effectiveness in weight loss. A 2022 analysis of 22 trials involving over 17,000 participants found that 50.2% achieved at least a 5% weight loss, while 17.5% experienced a ≥10% weight reduction compared to placebo. A subsequent 2023 review of 41 trials confirmed significant reductions in weight, BMI, and waist measurements.

Dr. Andres Acosta from the Mayo Clinic highlighted the long-standing use of GLP-1 RAs and the growing enthusiasm for their application in treating obesity. However, experts like Dr. Daniel Drucker from Mount Sinai Hospital caution that while these medications are highly effective, not everyone benefits. Approximately 10% of users may experience minimal weight loss or intolerable side effects.

Dr. Drucker said,

[W]e know some people don’t lose much weight when taking these medicines and others don’t feel well and can’t take them… [It’s} essential for us to identify who will be the best responders, as we do with medications for other conditions, such as cancer and cardiovascular disease.

Understanding obesity phenotypes

Dr. Acosta’s research has identified four obesity phenotypes that can guide treatment approaches:

• Hungry Gut (HG). Patients experience rapid gastric emptying and feel hungry shortly after meals.
• Hungry Brain. Individuals have impaired satiety and tend to overeat during meals.
• Emotional Hunger. Emotional or hedonic eating behaviors dominate.
• Slow Burn. Patients have a sluggish metabolism and burn fewer calories.

In a study of 312 patients, those receiving phenotype-specific treatments achieved significantly greater weight loss (15.9% vs. 9.0%) after one year. Acosta’s lab has developed a genetic test to predict the best responders to GLP-1 RAs, showing promise in identifying individuals who might benefit most. It’s licensed by Dr. Acosta’s lab and available through Phenomix Sciences.

His group has also studied which lifestyle interventions are most effective for each phenotype. Dr. Acosta said,

When a unique lifestyle intervention targeting each phenotype was applied, patients lost more weight and had greater metabolic improvement.

Concerns about side effects

Despite their benefits, GLP-1 RAs carry risks. Common side effects include nausea, diarrhea, and constipation, while more serious issues like pancreatitis and gallbladder diseases have been reported. Additionally, cases of compounded GLP-1 RAs from pharmacies have been linked to fatalities. These risks emphasize the need for cautious use, especially as discontinuation rates are high due to cost (over $12,000 annually) and side effects.

Optimizing treatment

Experts like Dr. Marc-Andre Cornier stress that GLP-1 RAs should be part of a broader strategy that includes lifestyle changes, such as a high-protein diet and resistance exercise to prevent muscle loss. Furthermore, precision medicine approaches tailored to individual phenotypes may enhance treatment success and minimize trial-and-error prescribing. Recently published recommendations can help healthcare experts guide patients taking GLP-1 RAs to optimize nutrition.

Public attitudes and sustainability

Despite rising interest, a recent survey found that most Americans prefer alternative methods, such as plant-based diets, over weight-loss injections. Moreover, many discontinue GLP-1 RAs within a year, raising concerns about long-term effectiveness and potential weight cycling.

Dr. Acosta highlighted the importance of identifying ideal candidates for these medications to maximize benefits while addressing cost and insurance coverage challenges. Tailored approaches are key to ensuring sustainable, effective obesity treatment.

Your responses and feedback are welcome!

Source: “As GLP-1 Use Surges, Clinicians Weigh Benefits and Risks,” Medscape, 11/22/24
Source: “Metabolic Bariatric Surgery in the Era of GLP-1 Receptor Agonists for Obesity Management,” JAMA Network, 10/25/24
Source: “Reasons for discontinuation of GLP1 receptor agonists…,” Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy, 9/29/17
Image by Towfiqu barbhuiya on Unsplash

GLP-1 Drugs — Are Alternatives Feasible? (Continued)

This post is a continuation of a recent post.

A probiotic supplement may also contain golden turmeric extract (anti-inflammatory), black pepper extract (for bioavailability), sunflower lecithin, and other natural ingredients which are said to provide additional benefits. A fiber, glucomannan, helps a person to feel full, and various ingredients promote thermogenesis, or actual heat inside the body, which literally burns calories (or possibly not.)

A typical brand of natural stuff combines several ingredients and does come with the possibility of side effects which however are said to be rare. They are bloating, headache, and gut imbalance (dysbiosis), a particularly disconcerting outcome because one never knows whether to expect constipation or diarrhea, and they are pretty much the opposite phenomena.

But even if that internal chaos occurs, it is said to improve within weeks. One is tempted to ask, how many weeks? Four weeks? That would be a month, or one-12th of a year, at least. Many people prefer to remain overweight and enjoy life, instead.

A USNews.com article names seven high-satiety foods (high in fiber, healthy fats, and protein) and assures that a diet rich in them will aid in reaching weight loss goals. They are oats, barley, legumes, eggs, Greek yogurt, avocado, and fish. It goes on to say,

Foods high in protein, fiber and healthy fats can trigger the release of GLP-1 hormones and other satiety-enhancing effects… Eating more of these foods is less expensive than weight loss medications and have none of the unwanted side effects.

Even better, a piece by Joe Cannon, who for three decades has advised people about how to stoke up their own innards to manufacture their own GLP-1, names a total of 31 such foods. There are major groups, like fermented foods (yogurt, kefir and kimchi) and high-fiber foods (beans, oats, and barley), as well as resistant starch, whey protein, phytonutrients, Spinach Thylakoid Extracts, certain nuts and seeds, extra virgin olive oil, and other esoteric ingredients.

Along with the substances already mentioned, he recommends Resveratrol, glutamine, Valine, glycine, arginine, tryptophan, and more. Cannon also also warns of what to stay away from, and adds,

While going the natural route may not produce as impressive weight loss as drugs like Ozempic (semaglutide), it’s also true that it will cost less, and the risk of side effects may be lower, too.

…[T]he fact that natural therapies work is valuable knowledge to those who cannot afford these medications and who are averse to taking drugs for weight loss purposes.

A WebMD.com article by Jessica Migala adds some important information, namely that GLP-1 production is aided by exercise because it also facilitates the production of insulin, giving the body’s cells energy — and although research is not definitive, this appears to also be true for patients with type 2 diabetes. “Exactly what’s going on needs further study,” the report says.

Migala warns that natural supplements cannot achieve the same results as the drugs will. Although berberine might do something, the trials that opinion is based on have all used different doses and durations, so the overall picture is not clear. Also, it can cause the same nausea, bloating, and constipation that GLP-1 drugs are known for. She writes,

[I]t’s clear what the prescription medications are supposed to do, and at specific doses. But supplements may rely on preliminary or incomplete data, so it’s less clear what effect they will have on you.

The author warns patients to keep their physicians aware of anything they are taking, because some herbs and other remedies might interfere with or accentuate the effects of some medications. If the supplement route is chosen, it is important to try just one at a time, in order to be able to get clear answers about exactly what is working, and where the cause of any side effects can be found.

Your responses and feedback are welcome!

Source: “Provitalize Side Effects: What are the Side Effects of Provitalize Probiotics?,” TheBBCoo.com, undated
Source: “7 Foods that Mimic the Effects of Ozempic and Other GLP-1 Drugs,” USNews.com, 07/17/24
Source: “31 Best Foods and Supplements That Raise GLP-1 Levels,” SupplementClarity.com, 05/11/24
Source: “Can You Boost GLP-1 Naturally?,” WebMD.com, 07/26/24
Image by Michał Parzuchowski on Unsplash

Gene Therapy for Childhood Obesity

Childhood Obesity News has been looking at various types of treatment for childhood obesity, including GLP-1 agonists, digital technology, and behavioral interventions. Now, let’s take a quick look at yet another promising treatment — gene therapy.

For the past four years, researchers at Shriners Children’s St. Louis have been exploring new methods to combat the impacts of childhood obesity. Led by Farshid Guilak, Ph.D., and Ruhang Tang, Ph.D., the research team has developed a promising approach using gene therapy. Their studies in mice have shown that this therapy can convert harmful fatty acids into beneficial ones, which may help children with obesity lower their risk of associated health problems, particularly arthritis.

The study, published in the Proceedings of the National Academy of Sciences, details a gene therapy technique called “fat-1 gene therapy,” which prevents metabolic dysfunction, cellular aging, and arthritis linked to obesity.

According to Dr. Guilak, excess weight is the top preventable risk factor for arthritis in children. The team’s findings highlight that it’s not only obesity itself but also the diet that contributes to arthritis risks. Specifically, the type of fatty acids children consume significantly affects their weight and health.

Dr. Tang explained that gene therapy involves using an adeno-associated virus (AAV) to introduce a gene coding for an enzyme into cells. This enzyme automatically transforms pro-inflammatory Omega-6 fatty acids into Omega-3 fatty acids, which are healthier for metabolism. Omega-3s — found in foods like fish and certain nuts — enhance metabolic health by improving insulin sensitivity, promoting fat breakdown, and reducing inflammation, potentially lowering the risk of diseases related to obesity. Natalia Harasymowicz, Ph.D., another study leader, noted that the therapy also reduces the number of inflammatory cells involved in obesity and arthritis.

The study specifically examined post-traumatic arthritis, a form common among children due to injuries such as knee meniscus tears. A single gene therapy injection was shown to significantly reduce the negative effects of a high-fat, Omega-6-heavy diet on both metabolic health and knee arthritis. The therapy also appeared to prevent early “aging” in the mice caused by diet-induced obesity.

Dr. Guilak said:

What we are observing is that obesity results in old knees in young patients… The modern diet, especially in the United States, tends to be high in Omega-6s and low in Omega-3s, which can lead to an imbalance, especially for kids… Arthritis can be a very painful and debilitating condition for children so we’re hopeful that this research will help reduce the risk of it developing and make treatments more effective. The implications for how this research might be used in the future are vast but we’re excited about the potential for it to help kids lead healthier lives.

The research team, led by Dr. Guilak, is now collaborating with the FDA, aiming to start clinical trials within the next three to five years.

Your responses and feedback are welcome!

Source: “Gene Therapy Method Converts Omega Fatty Acids to Combat Childhood Obesity,” Genetic Engineering & Biotechnology News, 10/14/24
Source: “Gene therapy for fat-1 prevents obesity-induced metabolic dysfunction, cellular senescence, and osteoarthritis,” PNAS.com, 10/14/24
Image by National Cancer Institute on Unsplash