Sarah Zhang has an article on The Atlantic about the latest analysis regarding the new crop of obesity drugs and what researchers are learning about how they work.
The nutshell version of the article might be that scientists were right about HOW the drug works but more research is finding they were wrong about WHERE it works. Drugs like Ozempic and Wegovy, known as GLP-1 drugs, supply a hormone to the patient’s system that mirrors the hormone the human gut generates to create a “full” sensation. The medications on the market delivery a much larger, longer lasting dose of that same hormone to mimic the signal sent by the hormone generated in the gut.
What research is finding is that the hormone generated in the gut is a much shorter acting variety - a half-life of minutes. The dose provided by these new drugs is much larger and longer lasting (a half-life of several days) AND primarily acts on the brain directly, leaving those higher levels in the brain.
There are many functions within the brain with receptors for GLP-1 and many areas that produce it. Scientists and doctors are finding patients taking these drugs for weight loss also find it curbs other appetites as well.
It took a long time for scientists to appreciate the extent of GLP-1 in the brain, Karolina Skibicka, a neuroscientist at Penn State, told me. (snip) Since then, in a series of clever experiments using rodents, scientists have been able to show that GLP-1 drugs likely act on the brain. They don’t seem to work, for example, to suppress appetite in mice whose brain GLP-1 receptors have been genetically erased. Moreover, the effects of GLP-1 extend beyond food: Rodents given the drugs will drink less alcohol and use less cocaine. Anecdotally, too, people on GLP-1 medications have reported spontaneously quitting drinking, smoking, shopping, and other addictive and compulsive behaviors.
Here’s where this new science has potentially MASSIVE impacts on public health.
If you’ve been paying attention lately, you’ll notice there are a LARGE number of massively obese people in America. Look on YouTube for videos of public crowds at outdoor concerts in the 1970s versus 2020s and the contrast is striking. Until now, one dominant theory as to why obesity has skyrocketed involves the skyrocketing share of heavily processed foods Americans eat, especially those utilizing high fructose corn syrup. That makes some sense.
However, another key change in the health realm over the last fifty years has been a skyrocketing share of Americans being prescribed anti-depressants - the category of drugs termed selective serotonin reuptake inhibitors or SSRIs. These medications have a crucial side effect in a large portion of the patients taking them… An immediate spike in body weight. In my extended-family experience, three different people were prescribed SSRIs and IMMEDIATELY began gaining serious weight – in one case, ten pounds per month – while on the medication.
Of course, SSRIs pose two other critical problems. First, most (all?) of these drugs have no defined “off-ramp.” They aren’t curing the chemical conditions that are CAUSING depression or anxiety, they simply alter the chemical balance as long as they are taken to temporary mask the original problem. That means very few patients take these drugs for a few months, reach a mental health equilibrium, then STOP taking the SSRI. They remain on the SSRI indefinitely. For YEARS.
The second problem is for some patients, SSRIs don’t continue to work indefinitely. A patient may be prescribed a drug, finally land on an appropriate dose for their level of symptoms after a few weeks / months of adjustments with their doctor, then remain at that dose for months, maybe years. Then, out of the blue, the drug may simply stop working. Like a light switch, in a matter of a day or two. This can cause the patient to “crash” back into an acute condition of depression or anxiety and trigger a flurry of conversations with the doctor to identify another alternative and re-balance dosage levels on that new drug.
But for as many months or years that one of these SSRIs was prescribed, the patient may be continuing to gain weight. Or, they may have plateaued at some higher weight and now cannot drop the weight regardless of how they try to eat or exercise. I’m pretty sure the average person who became 50 to 100 pounds overweight would experience many NEW reasons to be depressed – appearance, joint pains, inability to exercise, skyrocketing blood pressure, diabetes, heart issues, etc.
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This new news about how these weight loss drugs seem to be actually affecting the body to work seems to suggest a new strategy for doctors and patients. First, any patient prescribed anti-depressants who immediately begins exhibiting consistent weight gain should probably also be prescribed one of these GLP-1 drugs. If a patient is of normal weight but begins adding 5-10 pounds per month while on an SSRI, that additional weight will create health problems equally damaging to the patient over time as the mental health issues. This is ESPECIALLY true when SSRIs are being prescribed to people as young as 10-12 years old. To become massively obese in childhood is literally an early death sentence.
Second, one member of my family started Wegovy in November and described the impact the drug had on appetite. Within four hours of the first shot, the prior chronic HUNGRY signal turned off “like a light switch” and has never returned. I found that “like a light switch” description interesting because this family member has also gone through a series of SSRIs over the last 20 years and used that same metaphor to describe the feeling when one of those meds just stopped working. Coincidence? It’s starting to sound like these drugs all impact the same chemical processes in many of the same brain centers. Perhaps these new GLP-1 drugs should be prescribed INSTEAD of SSRIs for some patients.
This is total conjecture on my part and I know nothing about medicine. However, it seems unlikely that America has an epidemic of OBESITY and an epidemic of mental health conditions that have resulted in MILLIONS being prescribed drugs that TRIGGER extreme obesity in millions of patients and that those two problems are unrelated. The cost of the current approach for treating these problems is draining the coffers of employers and the government alike and the approach isn’t solving the problem. There are literally hundreds of billions of dollars to save if a better solution to both of these problems can be found that doesn’t reinforce both problems. Not to mention millions of lives that would be much improved.
WTH
