A number of FDA-approved weight-loss drugs have one thing in common: They are slightly effective. Among them are orlistat, phentermine-topiramate, and naltrexone-bupropion. I actually took a combination that worked for a while (fen-phen), but in 1997 the FDA banned it because it might cause heart valve problems. Yet as I recall, my body developed tolerance, and the weight rebounded. Likewise, when I first started taking the ADHD drug methylphenidate (Ritalin), I lost a ton of weight, but again, my body adjusted, and it came back.
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One medicine just approved in 2019, Plenity, helped clinical trial users lose about 6 percent of their body weight during a year, compared to 4 percent on placebo. So, in a 200-pound person, you’re talking four pounds over the dummy pill — not even noticeable. Yet it costs nearly $100 a month.
Finally, though, it seems we may have an entire class of drugs, called GLP-1 agonists, that cause significant and long-term weight loss. With about three-fourths of Americans overweight or obese, they’re bound to be popular, and, indeed, suppliers can’t keep up with the demand. They’ve even taken such steps as declaring that their drugs are not for weight loss.
Yet the European Medicines Agency (EMA) has ramped up its scrutiny of GLP-1 treatments, raising a safety signal about the potential risk that they could cause cancer. Never mind that the primary malignancy of concern, thyroid cancer, has an excellent survival rate — nor that studies indicate GLP-1s may help prevent certain cancers, both directly and indirectly.
GLP-1s Are Effective for Weight Loss
First approved by the FDA in 2005 for diabetes, the drugs are usually self-injected weekly into the stomach (or other body parts with fatty tissue), although there are dosing variations, and some come in pill form. You’ve almost certainly heard about them. That’s because they have become part of the lifestyle of the rich and famous, including billionaires Elon Musk of Twitter and Michael Rubin of Fanatics, both of whom certainly appear considerably slimmer.
Now there are a host of GLP-1 agonists specifically approved for diabetes that are being used off-label for weight loss (for a purpose other than that approved by the FDA), two approved specifically for weight loss, and others apparently very close to getting that stamp of approval.
The drugs mimic the action of a hormone called glucagon-like peptide 1. When blood sugar levels start to rise after someone eats, these drugs stimulate the body to produce more insulin. The extra insulin helps lower the blood sugar levels. Lower blood sugar levels are helpful for controlling type 2 diabetes, the kind that develops after birth. And lo! It appears that many of these diabetics are also losing weight.
It’s not clear how the GLP-1 drugs lead to weight loss, but they definitely help curb hunger, in part perhaps because they slow the movement of food from the stomach into the small intestine. As a result, you may feel full faster and longer, so you eat less.
Side effects are quite tolerable in most people and include general gastrointestinal distress, such as nausea, vomiting, and diarrhea.
Big Pharma, knowing a cash cow when it sees it, began testing the drugs at higher levels and in various formulations. Sure enough, they work. Quite well. The first approved for this purpose was Novo Nordisk’s Wegovy and Saxenda, while the same company’s Ozempic and Eli Lilly’s Mounjaro appear close to approval for weight loss.
A 2021 study showed that once-a-week injections of Wegovy over the course of 68 weeks caused about 15 percent weight loss in obese adult participants. The key ingredient in the original formulations was semaglutide, which stimulates GLP-1. But some of the drugs, such as Mounjaro, also contain a second hormone, glucose-dependent insulinotropic polypeptide. A clinical trial of Mounjaro, published in July 2022, showed more than 20 percent reduction in body weight in 2,539 adults over a 72-week period. The mean reduction in total body fat mass was a stunning 33.9 percent, compared to 8.2 percent with the placebo.
Meanwhile, Eli Lilly has just released results for its daily pill, orforglipron, which shows 15 percent weight loss at only 36 weeks with no apparent plateau, as opposed to similar results in twice the time with some injectables. Eli Lilly also has an injectable called retatrutide, which, in a phase two study, found that users lost an average of 58 pounds at the end of the 48-week trial. That’s a mean 24 percent reduction in participants’ body weight.
Yes, truly amazing results.
Ah, but what about that cancer stuff?
‘Miracle Drugs’ Could Help Prevent Cancer
There’s been no one action by the EMA. Rather, it “has ramped up its scrutiny of GLP-1 treatments, raising a safety signal about the potential risk that diabetes and obesity drugs could cause cancer,” notes FierceFarma, a website that covers the pharmaceutical industry. “The move is a first step for the regulator in monitoring the potential for adverse events that could be related to use of approved drugs.” The EMA has recently put numerous GLP-1 manufacturers on notice.
The FDA has long required a “black-box warning label” on GLP-1s for thyroid cancer, but it’s for thyroid cancer in rodents. As I observed in these pages recently, both positive and negative results in rodents rarely predict for humans, and that black box actually admits there’s no strong evidence for thyroid cancer in humans.
Humans? Well, a French study published this past February found the use of GLP-1 drugs “for 1-3 years was associated with increased risk of all thyroid cancers,” including 58 percent of all types of thyroid cancer and 78 percent of medullary ones. There are four types of thyroid cancer, and while medullary is relatively aggressive, it is also rare, composing about 4 percent of all thyroid cancers.
An accompanying editorial said this is consistent with previously reported data. But it also says that it may just reflect what’s called “detection bias.” Detection bias is a problem that can happen in cancer studies when the way that cancer is detected is not the same for all the groups being studied. This can make it look as though there are differences in how many people have cancer between the groups, even if this is not actually true. (READ MORE: My Generation Avoids Work: Here’s How That’s Impacting Mental Health)
This would apply to all such studies, not just the French one. The editorial concedes that there may actually be an increased risk but concludes, “Thyroid cancer is a rare outcome, however, and the potential increase in absolute risk is very small.” It adds: “Clinicians and patients need to always balance benefit and harm of treatments in light of their alternatives. In a population without specific risk factors for thyroid cancer, the benefits of [GLP-1s] will largely outweigh the harm.”
Eureka! What a great formula! Potential harm must be weighed against benefits! This is called a risk-risk analysis.
Further, if you decide to go ahead and get cancer, then thyroid, along with basal cell and squamous cell (skin), is the one to get. Five-year survival for thyroid cancer in the U.S. is 98 percent. This means it could probably be 100 percent if there were proper screening for earlier diagnoses and proper treatment. A friend of mine had it and avers that, along with the aforementioned skin cancers, it should really be considered more of a quasi-cancer. It fits the definition, but maybe the definition is wrong. (He’s also had basal cell carcinomas. This is a man who knows how to pick his cancers!)
There’s also been some concern regarding GLP-1s and pancreatic cancer, which we all know is very much a “cancer cancer,” especially since it’s almost always diagnosed in late stages. But the evidence here is even weaker. A recent meta-analysis of 12 studies published in the prestigious journal Nature found that “GLP-1 analogues did not increase the risk for pancreatic cancer when compared to the control.”
In fact, there is some evidence that GLP-1 drugs may directly help prevent cancer, and a boatload (as in a container ship) of evidence that it may do so indirectly.
Some research indicates that the direct impact may be from reactivating critical cancer-fighting immune cells that have become defective due to obesity. The boatload is that it’s long been known that obesity and being fat (not just obese) are powerfully related.
“Being overweight or having obesity are [sic] linked with a higher risk of getting 13 types of cancer. These cancers make up 40% of all cancers diagnosed in the United States each year,” says the CDC. According to recent research, “Obesity is considered the second most predictable and modifiable cause of cancer development after smoking.”
I devoted many pages to the cancer connection in my 1997 book The Fat of the Land: The Obesity Epidemic and How Americans Can Help Themselves. Further, the percentage of weight-related cancers is increasing because the percentage of overweight Americans is increasing, with the COVID pandemic fueling a sudden leap. Americans are also constantly shifting from overweight to obese and obese to morbidly obese. The fact is that the 40 percent cancer figure is somewhat outdated, and it could now be approaching half — if not yet, then give it a few years. We. Just. Keep. Getting. Fatter.
That’s not to mention all the other nasties overweight and obesity cause. “It has been widely established that elevated BMI is a serious risk factor for a number of chronic diseases, including diabetes mellitus, cardiovascular disease, chronic kidney disease and musculoskeletal disorders,” notes a study published last year. And, of course, it reportedly “increases the risk of severe illness from COVID.”
Weight Loss Hacks Could be the Domain of the Very Rich
The estimated annual medical cost of obesity in the United States was nearly $173 billion in 2019 dollars.
So let’s be clear: GLP-1 drugs are anti-cancer and pro-health generally. Indeed, one of the cancers obesity is related to is (drumroll, please!) thyroid! A review in the International Journal of Environmental Research and Public Health last year found that both incidence and death from thyroid cancer were clearly associated with being overweight, not just with obesity.
But why doesn’t that show up in the data linking GLP-1 use to increased thyroid cancer? Because that was in diabetics, not in people taking the higher levels to lose weight.
Something important not discussed regarding these drugs is that, for all the speculation about potential longevity drugs and supplements already available, none are proven. What’s proven? Weight in the low–normal range and moderate or vigorous exercise increase longevity. (Incidentally, “normal” means healthy. America’s normal is most certainly not.)
No drug can yet replace the benefits of exercise, but to the extent that GLP-1 drugs lower weight, they can be expected to extend the length and physical quality of life. Indeed, perhaps even put obese people in that nice range of “low–normal.” In other words, although they were originally meant to treat diabetes and are now seen as weight-loss drugs, we should consider GLP-1s lifespan drugs as well.
Really, it is all rather miraculous.
Caveats?
For one, most people will need to stay on the drug forever — although we can expect a minority to be so enamored of their weight loss that they find ways to maintain it even without the medicine.
Another is that some percentage of users will stop taking it because eating and overeating, especially overeating junk food, can be a lot of fun. Nobody reaches 300 pounds because they actually feel hungry.
A definite problem is that these drugs are quite expensive. Even the now-generic ones for diabetes tip the scales at about $400 at their lowest. Wegovy costs over $1,300 a month and is not covered by Medicare. Other GLP-1 formulations, therefore, will not be covered, either, which is a huge oversight given the plethora of diseases overweight and obesity cause. Medicaid may cover GLP-1s depending on the state. Individual plans almost certainly will not, which is not as shortsighted as it might seem. (READ MORE: The Feminist Infiltration of the Swimsuit)
Yes, the insured individual will have fewer medical costs. Medical costs for adults who had obesity are $1,861 higher than medical costs for people with healthy weight, according to recent data. But insurers don’t know when they will be paying those — it may well be another insurance company incurring those costs, or perhaps Medicare.
So for the indefinite future, unless you decide to become a diabetic just to get medical coverage of a GLP-1, they will remain the domain of the rich and famous, which is a shame. My quarter-century experience in this area indicates that individuals always have it in their power to maintain weight. But it’s rather harder than clicking one’s heels together. Meanwhile, obesity has become an epidemic. Where I live in the Philippines, people are generally dirt poor, but, especially since the lockdown, almost all of the young women are now overweight and have taken to wearing makeshift girdles and bikini bottoms like those from the ’50s to pull up over the gut.
Medical treatments are the only way to reign in the U.S. and worldwide obesity epidemics. They’re now available. It would be a shame if only Elon Musk and the like had access to them.
Michael Fumento (mfumento@outlook.com) has been an attorney, author, and science journalist for over 35 years. His work has appeared in the New York Times, the Washington Post, the Sunday Times, the Atlantic, and many other fora.
