If Novo Nordisk and Eli Lilly’s anti-diabetic and consequently anti-obesity drugs (GLP1) came as the blockbuster drugs the pharmaceutical industry was awaiting, they have since surpassed expectations by demonstrating capabilities in various other therapeutic areas from cancer to Alzheimer’s, some even calling it wonder drugs. To help us separate the hype from reality, here’s Derek Thompson taking us through what we know from research so far, how do they actually work and should we all be taking them if they are so good?
First, what do studies show?
“The most comprehensive analysis of GLP-1 drugs on a large population was published earlier this year. A team of scientists looked at more than 1 million patients with type 2 diabetes in the Veteran Affairs Medical System. They compared patients on GLP-1 drugs with those who been prescribed other meds. GLP-1 drug usage was associated with a reduced risk of … just about everything bad: “substance use and psychotic disorders, seizures, neuro-cognitive disorders (including Alzheimer’s disease and dementia), coagulation disorders [e.g., means clotting], cardio-metabolic disorders, infectious illnesses and several respiratory conditions.”
…Last year, a team of researchers at the Case Western Reserve University School of Medicine studied 1.6 million patients with type 2 diabetes and found that those on GLP-1 drugs had “significant risk reduction” of ten cancers: esophageal, colorectal, endometrial, gallbladder, kidney, liver, ovarian, and pancreatic cancer, as well as meningioma and multiple myeloma. “These drugs come out looking like superstars,” the Yale researcher F. Perry Wilson wrote. “As more data comes in, I become more convinced that we may look back on these drugs as the greatest medical breakthrough of the 21st century.””
How do they actually work?
“GLP-1 drugs stimulate the production of insulin (which reduces blood sugar) and suppress the release of glucagon (which tends to raise blood sugar). This makes it an ideal weapon against type 2 diabetes. We’re also pretty sure that the drugs work by slowing gastric emptying, which means that food stays in people’s stomachs for longer. Patients often feel full and rarely feel hungry. They frequently report less “food noise”—the constant worrying and planning around eating that’s reported by many people who struggle with their diet. With the combination of full stomachs and clear minds, calorie intake goes down, and weight follows.
But why should a drug that helps with insulin also help with memory? Why should a drug that makes you think less about food also reduce migraines and gambling compulsions and Parkinson’s symptoms?”
Thompson postulates three theories. The first is the simplistic one that obesity is known to be the root cause of many illnesses. So, by solving for obesity, GLP1 drugs effectively address the consequent ailments as well.
But the second theory is a little more scientific:
“…a dizzying number of our organs and tissues seem to have GLP-1 receptors (locks) that are ready to bind to these chemical agonists (keys). In our kidneys, GLP-1 activation seems to reduce local inflammation and improve renal function. Around our hearts, GLP-1s bind to receptors in cells lining our arteries, kicking off “a signaling cascade” that keeps blood flowing and reduces the risk of plaque accumulation and strokes. (GLP-1 receptors also seem to be strewn throughout our immune cells and neurons…)
The Canadian scientist Daniel Drucker has done more than practically anyone in the world to illuminate the benefits of GLP-1 drugs. In a recent essay in Science, he proposed that a “unifying” mechanism of these drugs could be the calming of bad inflammation. When our bodies notice germs or tissue damage, our immune response brings immune cells to the area. (Think about how your knee feels warm when you bang it; that’s normal inflammation.) But excessive chronic inflammation, which results from an immune system over-policing threats throughout the body, is a leading cause of organ damage, stroke, and neurological problems. GLP-1 drugs seem to bind to receptors throughout the body—in our gut, on our immune cells, and throughout the central nervous system—to broadcast the same message: STOP THE ATTACK! LESS INFLAMMATION, PLEASE!”
The third is through its effect on the nervous system and dopamine management:
“First, neurons throughout the central nervous system have GLP‑1 receptors, too. Activating these receptors protects nerve cells from damage and calms inflammation in the brain, just as they do throughout the body. .. Second, several experiments — whether they involve slices of brain tissue, animals, and even human volunteers — have strongly suggested that GLP-1 drugs specifically act on our dopamine cycles and affect neural activity in the hypothalamus, the appetite-controlling region of the brain. By acting as dopamine thermostats, they allow people to “turn down the volume” of their cravings and distractions.”
Yet, Thompson argues we shouldn’t jump to using them until further studies prove its safety from long term effects. We would urge you to read this last section in its entirety as Thompson is at his best relating it to the invention of the steam engine and its benefit to science even beyond the industrial revolution.
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