Welcome to Straight Talk on Health, I’m your host Dr. Chet Zelasko. Together with WGVU in Grand Rapids MI, I examine the world of health research and news. Whether it’s research that makes the news,
another miracle diet, a new food fad or an exercise trend, I look at the science behind them, and let you know whether it’s real or not. You can check out other things that I do on my website drchet.com and sign up for my free emails.
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. Even though they are a pharmaceutical approach to weight loss, they have 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. Here is what was unique about this particular study. At about the halfway point, they randomly selected some of the subjects to switch to a placebo without notifying them. Not unusual as those kinds of conditions are part of agreeing to be in research studies.
Those that were switched to placebo injections started to gain back the weight they lost. This was not just a “Get your injection and let’s see what happens. All subjects were supported with monthly consultations with dieticians to induce a 500 calorie deficit in food intake and increase exercise levels. As you might expect, 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? First, the public reaction.
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—and believe me, this is complicated. 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. There was no explanation as to why but perhaps the body has a tipping point. Too much refined carbohydrate keeping the production of the hormone high and it sort of wears out because it can’t keep up. Simplistic but possible.
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 glucagon-like peptide-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 glucagon-like peptide-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 earlier.
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 the price?
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 subjects in the placebo group were switched to an actual 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 research into this pharmaceutical intervention to out obesity issue 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 glucagon-like peptide-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. 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.
If you want to read more, two research papers have been published that are open access in 1. JAMA. 2021;325(14):1414-1425 and JAMA. 2022;327(2):138-150
