A problematic wonder drug

Overweight and obese Americans, who now comprise the majority of this country’s adults, just got some bad news from The BMJ, the journal of the British Medical Association.

In a lengthy, peer-reviewed, “systematic review and meta-analysis” published earlier this month, BMJ reported  that glucagon-like peptide-1 (GLP-1) receptor agonists – the weight-loss wonder drug of these times – work only so long as people continue to take the drug.

After reviewing 37 of 9,288 studies that followed up on GLP-1 patients over time, the researchers from the University of Oxford concluded “that cessation of weight management medications (WMM) is followed by rapid weight regain and reversal of beneficial effects on cardiometabolic markers. Regain after WMM was faster than after behavioural weight management programs. These findings suggest caution in short-term use of these drugs without a more comprehensive approach to weight management.”

The alternative, obviously, is to stay on the medications for life, which would be the dream scenario for the pharmaceutical industry, and an idea with which some, maybe many U.S. doctors, agree, if comments by physicians posting at MedPage Today are any indication.

After Dr. Christopher McGown, an obesity medicine specialist, wrote a MedPage commentary headlined “I No Longer Think GLP-1s Are the Answer – The drugs ‘work’ but may be working against us long-term,” there was a lot of blowback.

Doctors, nurses and other health specialists – the only people allowed to comment on the website – jumped into the comments below his story to compare GLP-1s for weight loss to other drugs that must be taken for life, such as insulin to treat diabetes or levothyroxin to treat an underperforming thyroid or any variety of drugs taken to treat high blood pressure and more.

The problem, according to some of those doctors, wasn’t in patients being required to be on a daily or weekly medication or, for many people, needing to be on yet another daily or weekly medication. No, the problem, in their view, was simply the high cost of GLP-1s such as semaglutide and tirzepatide,

As “texasdoc” observed in his comments, “patients simply need to be advised that these medications MUST be taken long-term, the same as with meds for other chronic conditions. Costs will come down over time just as with other innovations. The first telephones, the first automobiles, the first TV sets and the first portable phones were also expensive and ‘unsustainable.'”

Texasdoc was obviously not trained as an economist, because his comment displays a misunderstanding of how free markets work. The first automobiles, the first TV sets and the first portable phones were indeed expensive, but they were also sustainable.

As the Science Museum records, the first portable phone was the Motorola DynaTAC launched in 1984 and “affectionately known as The Brick…It quickly became a must-have accessory for wealthy financiers and entrepreneurs.

“The 1987 movie Wall Street cemented its status as an icon of wealth and greed when it showed ruthless financier Gordon Gekko, played by Michael Douglas, walking along a beach talking into his DynaTAC.”

Selling bling to rich folk is a perfectly sustainable business. The jewelry industry is built on that model. And the model worked for a long time for Motorola. The company made millions selling status icons.

For almost 20 years after it started selling its bricks, it pretty well owned the mobile phone market and then….

“Motorola’s rise and fall is a story of innovation followed by inertia, of missed opportunities, internal mismanagement, and a failure to adapt to the rapidly changing landscape of the mobile industry,” writes Paul Conant at Gizooom Consulting. “It’s a tale that reads like a classic American Greed episode, where once-glorious giants crumble under the weight of their own missteps. But more than anything, it’s a reminder that in business, being first isn’t always enough – you have to be able to stay first.”

Motorola’s decline came largely from its failure to recognize ongoing developments in personal computers, not phones. Personal computers quickly evolved from desktop to laptop and paved the way for the smartphones of today.

As everyone alive today knows, smartphones enable people to communicate by both voice and text, as they once did with now outdated pagers, and to connect to the internet. Hello Google!

Some will remember the meteoric rise and fall of the Blackberry, and everyone is familiar with the Apple iPhone, which first appeared in 2007 to change everything. It ushered in new technology and new production techniques. Competition followed as the market demand for lower-priced but similar products grew, and that is how we arrived at where we are today.

As of November, the Pew Research Center was reporting that 98 percent of Americans own a mobile phone, and 91 percent own a smartphone so that they can not only talk and text, but do all the things people do on the internet these days – shop, watch movies, video conferences with friends or associates, post on Facebook or X and more.

Costs will come down

For better or worse, some version of this could be the ultimate fate of GLP-1s, given that no one in the U.S. really wants to be overweight, let alone obese, and because many don’t want to be troubled by that  “comprehensive approach to weight management” that requires increases in physical activity or changes in diet or often both.

All indications are that the majority of Americans would like to spend a large part of their day sitting to watch screens, and then drive everywhere in motor vehicles, despite an average operating cost of more than $12,000 per year or a little over $1,000 a month, according to the Bureau of Labor Statistics.

And most of us would rather take a pill to lose weight than diet because dieting is hard.

I confess I would seriously consider taking a GLP-1 if not for the muscle-loss associated with the drugs and the cost. I love to hike and bike and, on occasion, still like to go for a run, even though the handicap of age tends to make the pace these days downright depressing.

Still, cycling, hiking and running are all easier when you’re hauling around less poundage, especially when the road or trail turns uphill.

Unfortuantely, there’s that GLP-1 trade-off of significant loss of muscle, which probably explains why these drugs have not to shown up in the regular testing of amazingly skinny, weight-obsessed Tour de France riders.

McGowan, an admitted “early and vocal advocate for GLP-1 therapy,” specifically warned of this problem in is column for MedPage.

“The adverse effects of stopping these medications extend beyond the scale, as evidence suggests certain risks…,” he wrote. “Take body composition: while on treatment, patients lose lean muscle along with fat, and studies suggest much of that muscle loss is never recovered.

“Upon discontinuation and subsequent weight regain, the regained weight is primarily fat, not muscle. This can leave patients worse off  – with less lean mass, a lower basal metabolic rate, and greater difficulty achieving future weight loss. Health consequences include diminished strength, reduced bone density, and a higher risk of fractures.”

There are also some other side effects, most commonly gastrointestinal distress of one sort or another and hair loss upon starting the medication. Plus other, rarer problems that have popped up, including possible gallbladder disease, kidney injury, pancreatitis, and thyroid cancer, according to the Mayo Clinic.

Still, these are all rare enough to make cost the biggest problem with the GLP-1s. Costs are now in the range of $700 to $800 per month and not covered by many health insurers.

University of Chicago researchers wondering whether the drugs were worth the cost this year undertook two studies that concluded that “their current prices far exceed accepted thresholds for cost-effectiveness, posing difficult choices for policymakers, insurers and patients.”

This conclusion came despite health economist David Kim, the senior author on the studies, recognizing that “these drugs don’t just help with weight loss. They also reduce the risk of cardiovascular disease, slow the progression of chronic kidney disease, and improve conditions like sleep apnea.”

Unfortunately, from a cost-effectiveness standpoint, diet and exercise are equal to or often better than GLP-1s for preventing cardiovascular disease, chronic kidney disease and a host of other chronic diseases, including various cancers.

And diet and exercise are cheap.

Pocket-book issues

So someone can get healthier by walking and cycling almost everywhere and saving all or a large part of that $12,000-plus per year in motor vehicle costs, or continue to drive everywhere and add $14,000 to $16,000 in GLP-1 costs to their yearly expenses to improve their health and look better.

No doubt, there are people to whom a $26,000 to $28,000 cost for convenience and appearance, forget health, might seem cheap. Others? Well, there are still places in this country where $26,000 to $28,000 per year would pay the mortgage on a home.

Thus many are, at this moment, are balking most at the cost of GLP-1s than anything else, and even if the cost were to be cut in half, many would likely consider themselves priced out of the GLP-1 weight-loss option.

So maybe it’s time for the government to step in, given that 75 percent of Americans are now considered to be overweight or obese. There’s no reason the government couldn’t take over production of GLP-1s and add them to the public water supplies, as the government did long ago with fluoride.

Of course, this wouldn’t end the fitness problem in a drive-everywhere country on the edge of being unable to field an army. The Department of Defense is now reporting that six out of 10 young Americans don’t qualify for enlistment because of obesity or lack of fitness, and the Centers for Disease Control says that among those ages 17 to 24 “only three in four report physical activity levels that prepare them for basic training.”

Younger Americans wouldn’t get any fitter GLP-1s were added to the public water supply. In fact, given the issue with muscle loss, they might even lose fitness. But all indications are that they’d be healthier – with GLP-1s credited with improving “cardiovascular, kidney, liver, arthritis, and sleep apnea disorders” – and they’d certainly look fitter.

Not to mention that the country might end the epidemic of childhold obestity now threatening American children and dooming many of them to a lifelong struggle with obesity.