Tag Archive for: pharmaceutical

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

It’s Official: Prescription Fish Oil

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The U.S. Food and Drug Administration approved the prescription fish oil Vascepa for expanded use on Friday, December 13. The approval for the medication is for the secondary prevention of cardiovascular disease in patients under the following conditions:

  • Triglycerides above 150 mg/dl for everyone with diagnosed CVD and taking a statin medication.
  • Diabetes and two or more additional risk factors for CVD along with taking a statin medication.

The modifiable risk factors for CVD include smoking, obesity, high cholesterol, hypertension, and sedentary living. Remember from our prior series, secondary prevention may help reduce the risk of CVD symptoms developing.

My concerns are the same as they were before. Triglycerides less than 250 mg/dl can be resolved by diet and exercise in most people. Because the mechanism of action is unknown as to how the prescription works, there’s no reason to think that reducing triglycerides by lifestyle change won’t work as well as the prescription; the clinical trial didn’t track this data.

Speaking of lifestyle change, keep in mind the website specials on the Optimal Performance program as we get ready for the New Year. The Basic Meal Plan will teach you how to change your diet to reduce triglyceride levels if your levels are too high.

What are you prepared to do today?

        Dr. Chet

References:
1. http://bit.ly/36EbsYK
2. N Engl J Med 2019;380:11-22. DOI: 10.1056/NEJMoa1812792.

Prescription Fish Oil: Questions Remain

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The REDUCE-IT clinical trial formed the basis for the expanded recommendations for use of Vascepa, the prescription fish-oil medication. This was an expensive trial, involving 11 countries and hundreds of medical centers with 999 physicians who recruited subjects, collected data, and kept track of the subjects for close to five years. With over 8,000 subjects, this was no easy task. As I said in Thursday’s Memo, they examined the primary and secondary prevention when the medication is taken with statins versus a placebo with statins.

While this was a tremendous effort, there are still some concerns, in my opinion.

Study Concerns

A board made up of physicians and the pharmaceutical company’s staff designed the study and helped execute it; the pharmaceutical company paid for the clinical trial, collected and managed the data, analyzed the data, and interpreted the results. Then the statistics were reviewed by an independent statistician. This creates a huge conflict of interest regardless of safeguards that may have been put in place.

When any type of study is supported by companies with vested interests in the outcome, there will always be questions. That has been true for every dietary supplement manufacturer that’s ever funded a study as well as the milk and sugar industry. It’s especially true for this study. I began by talking about a report from the financial sector. Billions of dollars are on the line. That has to be considered by the FDA before final approval is given.

I have a tendency to have faith in science, as skeptical as I may be at times. And that’s where my concerns lie; not in the financial aspect but in the study design and results.

My Concerns

As complicated as this study was, it was incomplete in my opinion. They did not collect any data on the subjects’ diet; a small change in diet could have reduced triglycerides (TG) enough to have a positive impact on secondary outcomes. The median change in TG over five years with the medication was 45 mg/dl, from about 215 down to 170 in the medication group, while it was reduced 13 mg/dl in the placebo group. We don’t know whether a group that focused on dietary changes to reduce TG would have the same reduction in CVD events; that would have been an excellent addition to the study design.

They also didn’t have a group using fish oil from dietary supplements. True, it’s not their responsibility, but we can’t know whether the same benefit might not occur if the dosing of EPA were equal:

  • Almost every study that has used fish oil to examine whether CVD outcomes could be reduced has used fish oil with 1 gram of EPA.
  • If the amount of EPA were the same, a head-to-head comparison between a supplement and medication that each had 4 grams EPA might have found a similar benefit.

The real issue is that we don’t know what makes the fish-oil medication work, just like we don’t know completely how dietary omega-3 fatty acids work. Is it just the reduction in the TG or how the oils work in the body? Are genetics involved? Diet? The microbiome? We have no idea at this time.

The Bottom Line

I’ll keep on eye on the approval process for this fish-oil pharmaceutical and let you know how it will be prescribed in the future. The decrease in TG found in the study can be done with lifestyle changes alone, so is it going to be worth the cost of a pharmaceutical for a slight reduction in CVD events? Remember the difference between medication and placebo was just 4.8%. If you fall in that category, you’ll have to decide for yourself: pharmaceutical fish oil or lifestyle change. In this case, a little work may go a long way.

What are you prepared to do today?

        Dr. Chet

P.S. This will be the last Memo until after Thanksgiving. Paula and I are doing something we haven’t done in 20 years: go on a real vacation, just us, just for fun. No work of any type. Talk to you again December 3.

Reference: N Engl J Med 2019;380:11-22. DOI: 10.1056/NEJMoa1812792.

Primary vs. Secondary Meds

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One of the key questions for the FDA advisory panel to consider was whether the prescription fish oil was a primary preventer of cardiovascular disease or a secondary preventer. What’s the difference? Primary prevention of CVD would impact the disease and stop events before they occurred in the subjects taking the fish-oil medication. Secondary prevention would prevent additional CVD events from happening in those with established CVD.

If you were a type 2 diabetic with an additional risk for CVD such as obesity or being a smoker, taking the prescription fish oil with a statin would prevent a heart attack or stroke from happening; that’s primary prevention. Based on the Reduction of Cardiovascular Events with Icosa-pent Ethyl–Intervention Trial (REDUCE-IT) that didn’t happen, but it did prove to be a secondary preventer of additional cardiac events in those subjects in the study with established disease.

The question is whether the FDA will approve the prescription fish oil as a primary prevention or a secondary prevention pharmaceutical. The advisory panel seemed split on that count. The assumption by some was that there was disease present even though the event had yet to occur. Others said “prove it” by doing an actual clinical trial to examine that question. We’ll find out how the FDA decides later this year. As I mentioned yesterday, the financial implications are huge.

There are still some things to consider with the clinical trial, and I’ll cover that on Saturday.

What are you prepared to do today?

        Dr. Chet

Reference: N Engl J Med 2019;380:11-22. DOI: 10.1056/NEJMoa1812792.