Tag Archive for: Ozempic

It’s Going to Be a While

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In the last Memo, When Will We Get Something Better?, we looked at research on a new drug to counter obesity. But don’t hold your breath.

The researchers developed a sophisticated algorithm and used AI to find the process and the potential obesity-protein hormone to help combat obesity. What’s next? Several years or longer of clinical trials to test its effectiveness and safety in human beings. If it works, it will be another pharmaceutical solution to obesity and a step better than the GLP-1 agonists currently available. Two of the researchers hold the patent for the process and the protein itself, but there are no shortcuts on the science.

In my opinion, the problem is this: that’s not really the solution. They’re looking for a pharmaceutical solution. This protein, called BRG for short, will still have to be regulated like a pharmaceutical, made like a pharmaceutical, and prescribed as such even though it’s a natural hormone made in the body.

Where the research should focus is on a natural way to stimulate the body to upregulate (turn on) the gene or genes with diet, exercise, or some other natural means. Turning specific genes on and off is where we want to be, not creating companies and chemicals that will create a single molecule. It’s just the wrong approach to me. It may very well work, but it’s not natural in any way. I’m not suggesting that people with massive obesity won’t benefit from it, but it’s treating the symptoms of the problem, not the problem itself.

The problem is that because we overeat the wrong foods while not moving enough, genes have become upregulated and stay that way. We need solutions that help us get to downregulating those genes so that weight loss can become permanent.  Eat less. Eat better. Move more. For life.

What are you prepared to do today?

        Dr. Chet

References:
1. https://med.stanford.edu/news/all-news/2025/03/ozempic-rival.html
2. Nature (2025). https://doi.org/10.1038/s41586-025-08683-y

When Will We Get Something Better?

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The quest for a pharmacological solution to obesity continues—the magic pill to make us thin. While Ozempic and Wegovy, discovered and developed to treat type 2 diabetes, have been successful in helping reduce HbA1c, it has also helped people lose weight; the problem is the side effects. As you might guess, there are receptors for GLP-1 agonists in numerous locations in addition to the brain, and other organs are impacted.

That’s why a press release from Stanford seemed promising: “Naturally occurring molecule rivals Ozempic in weight loss, sidesteps side effects.” This research used a unique approach: they designed a specific algorithm that used artificial intelligence to identify the hormone segments made by an enzyme prohormone convertase 1/3 (PC1/3); basically, it cuts prohormones into smaller segments. Some may have metabolic activity, most would not.

Based on the analysis of 2,600 protein segments, the researchers identified 373 potentials and tested the top 100 most likely to succeed. They identified a hormone segment with 12 amino acids that appears to impact hunger 10 times better than the GLP-1 agonists, which are cleaved from the same prohormone. When they tested it in mice and minipigs by injecting it into the muscles of the animals before eating, it reduced food intake by 50%.

The volume of work done by the specific algorithm using AI probably saved years compared to testing each prohormone by trial and error, but what’s next? When will it be available? I’ll cover that on Saturday.

What are you prepared to do today?

        Dr. Chet

References:
1. https://med.stanford.edu/news/all-news/2025/03/ozempic-rival.html
2. Nature (2025). https://doi.org/10.1038/s41586-025-08683-y

Why Scientific Research Must Never Stop

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The current U.S. administration has tried to stop or delay basic and clinical research related to human conditions and diseases, and in the next few Memos, I’m going to illustrate why that’s a serious mistake. When I’ve laid it out, you can decide for yourself whether clinical research is a waste of money or critical for human health and well-being.

Example One: Glucagon-like Peptides

Sometime during the last century, chemicals were found in the intestines that seemed to increase the release of insulin in response to glucose. It wasn’t until the early 1980s that a gene was identified that resulted in the manufacture of proglucagon. Continued research found that when the protein was unfolded, it was responsible for the production of six different hormones. While all are important, one in particular has become popular 40 years later: GLP-1 (glucagon-like peptide-1). Depending on where it’s produced, its major function is to increase satiety by delaying digestion in the stomach. The net effect is to reduce food intake; that impacts glucose levels in people with pre-diabetes and type 2 diabetes, which can lead to weight loss and the possible prevention of every other condition downstream from diabetes such as cardiovascular disease or diabetic neuropathy.

You may recognize GLP-1 agonists, chemicals which will turn the production on, by their brand names such as Ozempic and Trulicity. They are helping millions of people control their type 2 diabetes with a side benefit of weight loss. From the time that the chemical was discovered, through identifying the gene that produces it, and the development of a chemical that could stimulate the gene to produce GLP-1, the process took over 50 years. The scientists began with basic research and ended with clinical trials to prove the efficacy of the medication. And the research is still not done—if research is able to continue to find something that stimulates only GLP-1 receptors in specific locations in the body instead of systemically, side effects could be controlled more effectively.

Another illustration on Saturday. Tomorrow is the March Insider Conference Call. The primary topic will be more detail on how drugs like Ozempic work as well as answering your questions. Maybe it’s time you become an Insider and join the call.

What are you prepared to do today?

        Dr. Chet

Reference: J Clin Invest. 2017 Dec 1;127(12):4217–4227. doi: 10.1172/JCI97233

Is It Worth It?

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At an obesity conference, the report on the clinical trials for a pre-diabetes and diabetes medication left the crowd on their feet and cheering. There are reports of well-known personalities who’ve used the drug with great results. But the ultimate question about a pharmaceutical approach to obesity has to be this: is it worth the money? Let’s start by looking at the pharmaceutical and then the return on investment.

How It Works

The body makes proteins called incretins which can stimulate the release of insulin. One incretin hormone, GLP-1 (glucagon-like peptide-1), is manufactured in the upper digestive system in response to carbohydrate intake. In subjects with type 2 diabetes, this hormone effect is diminished or no longer present.

The ability to stimulate the production of insulin and prevent the release of glucose by glucagon can be stimulated pharmacologically by semaglutide, a receptor agonist—that means it turns on the glucagon. In subjects with type 2 diabetes, semaglutide stimulates GLP-1 receptors significantly, thereby reducing blood glucose and improving glycemic control. In addition, it has multiple effects on various organ systems; most relevant are a reduction in appetite and food intake, leading to weight loss in the long term. Since GLP-1 secretion from the gut seems to be impaired in obese subjects, it was logical to test it in obese populations. Those were the study results I reported on Tuesday.

All in all, this sounds like it might be a potential solution to our obesity crisis, but there are some unanswered questions. What is the long-term safety of regular use of the drug? How does the microbiome impact the effectiveness of the drug? But more than that, everything comes with a price, which begs the question: is it worth it?

The Price

The price of using semaglutide for obesity is really two-fold. First is the actual cost of the weekly injections which is about $1,400 per month at retail. If your insurance will cover it, I’ve seen prices as low as $25 per month. We know that people lost an average of 18% of their starting weight at 68 weeks—the length of the longest study to date—but the rate of weight loss declined near the end of the study. How long will insurance cover it beyond that, and will a person continue to lose weight? We don’t know.

After using the drug for 20 weeks, the placebo group was switched to a placebo and immediately began to gain weight. By the end of 68 weeks, they had regained all but 5% and were still gaining. Would an investment of close to $17,000 to lose about 20% of your weight be worth it if you began to gain it back? There are many questions around whether people can take this drug for the rest of their lives; every pharmaceutical intervention must have an end strategy. The researchers did not address the issue.

The Bottom Line

The research into this pharmaceutical intervention was well done. However, unless the intervention includes an exit strategy, it could be a waste of money. Perhaps a lower carbohydrate diet may be a partial solution because this drug impacts carbohydrate metabolism. But we don’t know whether the weight loss would be enough to have the body take over and do the same thing on GP-1 by itself.

I think this shows a hopeful approach and it may turn out to be a boost to someone who is absolutely willing to change their lifestyle or someone who needs to lose weight for a specific purpose, such as joint replacement surgery or preparing for IVF. But for most of us, maybe it’s better to save the time and money and do what we know works: Eat less. Eat better. Move more.

What are you prepared to do today?

        Dr. Chet

References:
1. JAMA. 2021;325(14):1414-1425. doi:10.1001/jama.2021.3224
2. JAMA. 2022;327(2):138-150. doi:10.1001/jama.2021.23619

Happy New Year!

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It’s good to be back talking to all of you again. The New Year is a time of optimism, everything seems possible, and there’s an enthusiasm for achieving health goals. One thing many people want to do is to lose some weight. It seems appropriate to cover a couple of drugs that were recently approved by the FDA to treat obesity. They’re a pharmaceutical approach to weight loss, and they’ve gotten so much press I have to cover them.

You’ve probably seen the commercials for a pre-diabetes and diabetes medication called Ozempic. It also has a sister drug called Wegovy that was approved for use in teens. In at least two clinical trials, subjects who had weekly injections of the drug lost at least 15% or more of their body weight in 68 weeks. Those who were switched to placebo injections started to gain back the weight they lost. All subjects were supported with monthly consultations with dieticians to induce a 500-calorie reduction in food intake and to increase exercise levels. Markers for type 2 diabetes improved such as HbA1c and blood glucose.

Is this the be-all and end-all to the obesity epidemic? And exactly how does this drug work? I’ll cover that on Saturday.

What are you prepared to do today?

        Dr. Chet

References:
1. JAMA. 2021;325(14):1414-1425. doi:10.1001/jama.2021.3224
2. JAMA. 2022;327(2):138-150. doi:10.1001/jama.2021.23619