The mainstream media has showered enormous, almost unprecedented attention on a new class of GLP-1 agonists, including semaglutide, sold as Ozempic for diabetes or Wegovy for weight loss, and tirzepatide, sold as Mounjaro and Zepbound. These GLP-1 mimics have been called “the medical sensation of the decade,” and the business press has been practically giddy, boldly declaring “the end of obesity.” What are these purported panaceas? Are they truly magic pills?

 

First, What Is GLP-1?

Glucagon-like peptide-1 (GLP-1) is a naturally occurring hormone in our body that helps regulate digestion and blood sugar. It also suppresses our appetite by targeting parts of the brain responsible for cravings and hunger.

Signaling satiety to our brain is GLP-1’s main action, but it also slows our digestion. When the rate at which food leaves our stomach is delayed, we not only feel fuller for longer, but our blood sugar control benefits, too. And, indeed, when GLP-1 or an agonist is dripped into our veins, appetite drops and significantly less food is consumed—a decrease in caloric intake by as much as 25 to 50 percent.

 

What Stimulates Section of GLP-1?

GLP-1 is released by our gastrointestinal tract, along with more than 20 other peptide hormones. Meals heavy in carbohydrates and fats are the primary stimuli for GLP-1 secretion, but plant-based meals can more than double GLP-1 secretion, compared to a meat meal.

 

Signaling GLP-1 Naturally

When we eat a cupcake, our body absorbs the sugar, starch, and fat quickly, but the cells that produce our appetite-suppressing hormone are concentrated further down our digestive tract. So, most of our GLP-1 is produced at the end, but much of the calories we consume are absorbed early on and most never even make it down far enough to stimulate GLP-1 secretion. This is why we may not feel sated. When it comes to GLP-1, when we eat that cupcake, it’s as if we never ate much of anything at all.

It is believed that our prehistoric ancestors consumed as much as a hundred grams of fiber a day, which is more than six times what most of us get now. Throughout our evolution, we ate massive amounts of whole plant foods, which are the only places that fiber can be found in abundance. This allowed our natural satiety mechanisms, including the release of GLP-1, to prevent us from overeating and helps explains why a whole food, plant-based diet has been shown in the medical literature to lead to greater average weight loss than any other way of eating that didn’t involve portion control.

 

What About GLP-1-Mimicking Drugs?

Isn’t it easier to take a pill or get an injection than eat a lot of plants? We cannot take GLP-1 directly because our body breaks down the hormone so rapidly that it barely makes it around our circulatory system a single time. Then, a compound was found in the venomous saliva of the Gila monster lizard that mimics GLP-1 but is resistant to breakdown. From that realization, the first GLP-1 agonist was created, mimicking the hormone’s action by binding to GLP-1 receptors, and approved for diabetes treatment about two decades ago.

 

How Do GLP-1 Weight-Loss Drugs Work?

GLP-1 agonist drugs work similarly to birth control pills. The Pill mimics placental hormones and tricks our body into thinking we’re pregnant. Ozempic-type drugs mimic GLP-1 and trick our body into thinking we’re eating all the time. That’s how they lower our hunger drive.

 

Are GLP-1 Weight-Loss Drugs Effective?

More than 17,000 people individuals were randomized to injections of either high-dose semaglutide or placebo for four years in the longest trial to date. Overall, the individuals on the drug lost 9 percent more body weight than those in the placebo group, but all the weight was lost in the first 65 weeks. Despite continuing to get injected weekly for three additional years, they did not lose any more weight over the following 143 weeks.

With GLP-1 drugs, the weight loss caused by the initial drop in appetite is typically undercut by a significant increase in caloric intake as our body ratchets up our hunger again. Within a year, this resistance, combined with the decreased caloric needs from being lighter, matches the persistent effort to cut calories, causing weight loss to plateau. What’s more, as soon as the drugs are stopped, our full appetite resumes and we start regaining the weight we initially lost.

 

Side Effects of GLP-1 Type Drugs

There are myriad side effects of these GLP-1 mimics, and the most common are nausea, vomiting, diarrhea, and constipation. Rare but serious adverse effects are also emerging. The package inserts for both semaglutide and tirzepatide list “warnings and precautions” that include thyroid tumors, acute inflammation of the pancreas (pancreatitis), acute gallbladder disease, acute kidney injury (that may stem from dehydration due to excess vomiting or diarrhea), allergic reactions, a heightened risk of bottoming out blood sugars while on blood sugar–lowering medications, worsening eye disease for those with type 2 diabetes, an increase in heart rate requiring monitoring, and suicidal thoughts and behaviors.,

 

Are GLP-1 Weight-Loss Drugs Safe?

In the first quantitative benefit-versus-harm balance analysis, the researchers concluded that those achieving a 10 percent weight loss had a more than 90 percent chance that the benefits of taking the drugs outweigh the harms, but the opposite was found for individuals achieving only a 5 percent weight loss.

Presently, we simply do not know about any long-term benefits or harms because some of these drugs and dosing schedules are so new. What’s more, the American Academy of Pediatrics has suggested offering these GLP-1 agonists to teens and even tweens as young as age 12. As these drugs work by acting on the brain, we don’t know what effect they might have on childhood development and beyond. There may be evidence of near-term benefit over a few years, but long-term safety can’t be assumed until it has been demonstrated.

 

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