Tag Archive for: insulin

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

It’s All About the Calories

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The paper advocating the carbohydrate-insulin model (CIM) for explaining the obesity pandemic, not only in the U.S. but throughout the world, was written by the leading experts in endocrinology and nutrition. There were experts who’ve conducted some of the major nutritional studies that you’ve heard about over the years, from the Women’s Health Initiative to studies on the ketogenic diet. This is an expert group.

I agree with their desire for more research in this area. They’re trying to find out what would constitute their definition of cause: what increases appetite? Does palatability drive food choices? What hormones impact how much a person eats? And more. Where I disagree is in their lack of acknowledgement of the energy balance model (EBM) as valid. I outlined a written response to send to the journal that would have been about five pages long. Here are my two primary arguments.

Prior Research on Weight Loss

The authors talk about prior research showing that a low-fat diet doesn’t work long term; one of the authors was heavily involved in the weight loss study on a low-fat diet in the Women’s Health initiative. Their analysis was incorrect. The objective of that study was to compare a group of normally fed women eating the typical American diet of close to 40% fat with a group who was going to lower their fat intake to 20%. In the analysis, there were no differences in weight loss over the course of the study. The results suggested that a low-fat diet doesn’t work.

Here’s the problem: looking at the data from that study, what you see is that the women who were supposed to achieve a 20% fat intake couldn’t get below 28%. That doesn’t meet the goals of the study and thus doesn’t support their conclusion.

The Minnesota Starvation Experiment

My primary argument goes back to the research done on conscientious objectors during World War II. I’ve talked about this fascinating study many times, but here’s the short version: for a period of six months, 36 men who were conscientious objectors had their caloric intake cut by 25%. Their physical activity was also increased; they had to walk up to 22 miles per week.

What was unique was that they were weighed every week and their caloric intake adjusted based on weight loss or weight gain. If they did not lose the required amount, they were given less food. If they lost too much, they were given more food.

What makes that study even more consequential is the types of food that they were given to eat. The menu was very low fat and had virtually no protein; it consisted of breads and starches from root vegetables. In the CIM, that would be just about the worst types of food to eat to lose weight. But remember, the purpose of that study was to feed people foods that would be available after the end of the war. Every subject lost weight and lost it on a linear basis; most emerged looking emaciated. That’s the only study I’ve ever seen where people lost weight in a linear fashion over that period of time, and they did it eating an almost 100% carbohydrate diet.

The Bottom Line

There are many other aspects of the paper that I could comment on, but those are my two strongest points. I do believe that insulin is the most powerful hormone in the body; it does help store food as fat if someone overeats for an extended period of time. That makes it more difficult to sustain weight loss until the body is retrained to lose weight and keep it off.

But let me be clear: it always was, it is, and it always will be about the calories regardless of the source. Eat too many and you gain weight. Eat fewer and you lose weight. For sure, make better choices on the selection of the food that you eat and move more. But it’s all about the calories. Period.

What are you prepared to do today?

        Dr. Chet

Reference: AJCN. 2021. doi: https://doi.org/10.1093/ajcn/nqab270.

The Weight Loss Battle: Carbs vs Calories

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As a member of the American Society of Nutrition, I get a news feed that lets me know what’s being published in their journals. A recent article talked about the carbohydrate-insulin model (CIM) as a cause of the obesity pandemic. The debate surrounded the question of whether the energy balance model (EBM) that says calories in should equal calories out is adequate to explain the 70% overweight population in the U.S. Instead, a large group of researchers suggested that it’s time to research insulin as it relates to the highly refined carbohydrate intake of the population as the actual cause of obesity.

But that’s not all. The article suggested that insulin causes the body to store excess carbs as fat. More than that, to maintain blood sugars, it forces people to eat more carbs because they’re actually being starved, which drives hunger and is actually responsible for obesity. They went on to explain the fallacy of the EBM model and to deal with the criticism of the CIM model. In actuality, the researchers want to study the CIM approach, and this was a call for research to find out what really causes obesity.

To say it didn’t sit well in the nutrition and medical community is an understatement. Over 100K responses were generated in a couple of weeks, and I guess the nutrition Twitter world went nuts. Why? This is actually a battle over the ketogenic diet and everything else that focuses on counting calories. I’ll give you my opinion and why I believe what I do on Saturday.

The Insider Conference call is tomorrow night at 9 p.m. Eastern. If you have questions about your health or products, become an Insider before 8 p.m. and you can participate. Even if you only want to listen, you’ll learn something new to improve your health and the health of others you know.

What are you prepared to do today?

        Dr. Chet

Reference: AJCN. 2021. doi: https://doi.org/10.1093/ajcn/nqab270.

Obesity Game Changer?

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Obesity is a serious issue in the U.S. and around the world; type 2 diabetes, hypertension, CVD, and other diseases associated with obesity have significant health costs. That’s why a real game changer would be important to help people lose weight and maintain their weight loss. The latest candidate is semaglutide, an anti-diabetic medication used for the treatment of type 2 diabetes by increasing insulin secretion. In my opinion, the results of this study do not achieve game-changing status. Let’s take a look at the details.

There Was Limited Weight Loss

The mean weight loss was 14.9% which translated to 34 pounds in 68 weeks. That’s really not impressive; most people can lose a half pound a week by paying more attention to their diet and increasing their activity level. The rate of weight loss in the placebo group stabilized at about 20 weeks, and that’s where it stayed for the rest of the study. In the experimental group, the rate of weight loss declined twice; first at about 20 weeks and then again at 52 weeks. By 60 weeks, the experimental subjects did not appear to be losing any more weight.

The Lifestyle-Change Program Was Ineffective

With 35 years of experience in weight loss programs, my hunch is that by 20 weeks, both the placebo and the experimental group had reverted to their prior eating patterns. We don’t know for sure because no nutritional data were presented, but that would explain the lack of continued weight loss in the placebo group and slowing weight loss in the experimental group. The drug may be game-changing, but without permanent lifestyle changes, it’s just another weight loss drug.

The medication was effective in continuing weight loss in the experimental groups, but we don’t know how. Insulin is the most powerful hormone in the body, but we don’t know exactly how semaglutide helped these subjects lose weight. Did it influence appetite? Did it impact insulin levels alone?

At What Price?

The lowest price I could find with insurance coverage was $800 per month. This would be cost-prohibitive for most people. Another way of looking at: it cost $376 per pound of weight lost. I’m not sure that’s worth the price because we still don’t know if the drug will help maintain the loss for a significant period.

And besides the monetary cost, what physical cost did the drug have? Every drug has side effects. That’s why in most cases I recommend trying lifestyle changes before adding a medication; if unhealthy habits helped create the problem, changing those habits is the best place to start. Even if a healthier diet and increased activity don’t solve the problem, those changes may mean you can take a lower dose of the med, thus reducing side effects. Except in urgent cases, most doctors will give you some time to try lifestyle changes before adding a medication.

The Bottom Line

I consider the study a failure because the subjects in both groups never learned how to change their food intake and exercise behaviors. Yes, those people taking the pharmaceutical did better related to weight loss, and because of that, some metabolic factors improved. But the rate of weight loss slowed down as the study progressed and eventually appeared to stop. Maybe this drug will give some people an edge with initial weight loss and thus improve their odds of long-term success, but if they don’t permanently change their behaviors, they won’t permanently lose weight.

We have to quit thinking of a healthier diet as a temporary change. The challenge is not losing weight; the challenge is in maintaining the lost weight. If you go back to your old eating habits, you’ll go back to your old weight; if you won’t commit to changing your diet and activity, taking a pill isn’t going to help you for very long.

While interesting, this study doesn’t change the game. The game was, is, and always will be eat better, eat less, and move more. For life.

What are you prepared to do today?

        Dr. Chet

Reference: NEJM. 2021. DOI: 10.1056/NEJMoa2032183

“Game-Changing” Treatment for Obesity!

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If ever a health headline gets your attention, it’s one that proclaims there’s a better way to lose weight. “A game changer” said one of the principle authors of the study in a news release about the study. The results of any study that suggests “game-changing results” just has to be reviewed, and that’s what I’ll do in this week’s Memos.

The study was a trial of 1,961 subjects conducted at 129 sites around the world. The subjects were randomly assigned to the experimental group and placebo group in a 2:1 ratio. The experimental group received once-weekly injections of semaglutide, currently approved as a diabetes treatment, while the controls were injected with a placebo. Both groups received individual counseling sessions every four weeks to help them adhere to a reduced-calorie diet and increased physical activity. The study was 68 weeks long.

After 68 weeks, the mean change in body weight from baseline to week 68 was 14.9% or 34 pounds in the semaglutide group as compared with 2.4% in the placebo or about six pounds. Anthropometric measures, BMI, and cardiovascular and metabolic measures were better in the semaglutide group compared to the controls.

The results of the trial have already caused the manufacturer to apply for a rapid approval review as a weight loss drug. The question is this: is it really a game changer in the treatment for obesity? I’ll talk about that on Saturday.

What are you prepared to do today?

        Dr. Chet

Reference: NEJM. 2021. DOI: 10.1056/NEJMoa2032183

Essential Amino Acids: The Basics

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I’ve been getting many questions about essential amino acids lately. What are they? Why do I need them? Are they only for athletes? What can they do for me? In addition, I came across an interesting study that supports the use of EAAs in a specific population.

The EAAs include the amino acids phenylalanine, threonine, tryptophan, methionine, lysine, histidine, leucine, isoleucine, and valine. They’re essential because we can’t make them, but we can make other amino acids from these EAAs. In addition, three of the EAAs are designated as branch chain amino acids (BCAAs): leucine, isoleucine, and valine; they’re known as protein-building amino acids and important for building muscle.

Think of the EAAs as the rate-limiting amino acids. If we don’t have enough of them, we can’t make the other amino acids and thus, every protein made in the body can be affected. We often think only in terms of muscle, but the lack of EAAs could affect the manufacture of insulin, human growth hormone, leptin, and adiponectin to name just a few.

BCAAs have been marketed to athletes who are training to make muscle for years. Recently, EAAs have entered the arena because of their ability to make proteins that support muscle building. But that’s not the only group that may benefit as a recent study demonstrated. I’ll cover that on Thursday.

What are you prepared to do today?

Dr. Chet

 

Happy Fat Tuesday!

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Today is Mardi Gras—in case anyone doesn’t know, Fat Tuesday is the literal meaning of the French term. It’s the final celebration before the period of Lent that culminates in Easter Sunday. Many Christians use this time to give up something they enjoy as a sacrifice. The idea is to reflect and focus on our spiritual self; no matter your beliefs, giving up something you enjoy to focus on your inner self is a good idea. This week, I’m going to talk about giving up three typical categories of food and drink: sugar, salt, and alcohol. What benefits could you gain in the 40 or so days of abstinence from these foods? What may be a healthier substitute?

Let’s start with sugar, and by that I mean cake, cookies, donuts, sweet rolls, pies, ice cream, and candy. These are the ultimate in refined carbohydrates. If you were to abstain from these foods for 40 days, several things could happen. First, your insulin levels would probably drop because you wouldn’t have high levels of sugar hitting your bloodstream. If you’re prediabetic, you might see your triglyceride and HbA1c levels decline. If you had a fatty liver, it would most likely begin to clear up.

What could you substitute that would be healthier? Berries, fresh or frozen, any type, and you could even put a tablespoon of whipped cream on them. The antioxidants and phytonutrients would be better than the refined sugar; fruit sugar is processed differently, so it would not affect your blood sugar. Second choice would be citrus, and third would be apples.

If you’re considering giving up something for the next 40 days or so, make sure it’s something you really enjoy and eat regularly. Paula has a friend from Montana whose father, years ago before every food was available year round, gave up watermelon every Lent. It has to be meaningful.

What are you prepared to do today?

 

Dr. Chet

 

Prediabetes: What Now?

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The messages this week have talked about the risk factors for prediabetes and how many people don’t know what they are. It’s time to change that, at least in those of you who read the messages. Please feel free to pass them along to anyone you feel might also be unaware.

How do you know if you’re actually prediabetic? It requires a blood test for a specific protein called HbA1c. This protein indicates the amount of sugar that’s been in your blood stream for the past 90 days. The number for your blood sugar might be . . .

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