Ozempic and others in a new class of weight-loss drugs have been called “the medical sensation of the decade.” Are they worthy of all the hype?
For a deep dive, please see my primer on this topic. OZEMPIC: Risks, Benefits, and Natural Alternatives to GLP-1 Weight-Loss Drugs is available as an ebook, audiobook, and paperback. You can also view my video series for free on the Ozempic topic page or our YouTube channel. Here are some of the key takeaways.
What Is GLP-1?
A naturally occurring hormone in our body, glucagon-like peptide-1 (GLP-1) plays a role in regulating our blood sugar, appetite, and digestion. Our gastrointestinal tract releases more than 20 different peptide hormones, including GLP-1. The primary stimuli for secreting GLP-1 are meals rich in fats and carbohydrates, and GLP-1’s main action is to signal satiety to the brain. It also slows our digestion. Delaying the rate at which food leaves our stomach not only helps us feel fuller for longer, but also helps with our blood sugar control. When GLP-1 or an agonist (mimic) is dripped into people’s veins, appetite is reduced, leading to markedly reduced food consumption—a decrease in caloric intake by as much as 25 to 50 percent.
About GLP-1 Drugs
Our GLP-1 hormone acts as an appetite suppressant by targeting parts of the brain responsible for hunger and cravings. GLP-1-secreting cells don’t only line our intestines; they’re also in our brains. These new anti-obesity drugs are GLP-1 agonists, mimicking the hormone’s action by binding to GLP-1 receptors.
Our body breaks down GLP-1 so quickly that it hardly makes it even one time around our circulatory system, which is why we can’t just take the hormone directly. A compound was discovered—in the venomous saliva of a lizard called the Gila monster—that mimics GLP-1 but is resistant to breakdown. Using that compound as a template, the first GLP-1 agonist was created and approved for the treatment of diabetes about 20 years ago. Instead of most of it being cleared from the body within two and a half minutes, like native, natural GLP-1, much of the drug remains in the body for two and a half hours. That still means twice-daily injections, though, so then came liraglutide, which lasts all day.
What Is Ozempic?
Eventually, semaglutide was developed and branded as Ozempic, which could be injected just once a week. Ozempic was approved in 2017 to treat diabetes. Within a few years, a daily oral version had been developed, again for diabetes, but researchers running those clinical trials noticed a surprising side effect: People’s appetites diminished.
How Does Ozempic Work?
In a way, GLP-1 agonist drugs work like birth control pills. The Pill mimics placental hormones, thereby tricking our body into thinking we’re pregnant all the time. Ozempic-type drugs mimic GLP-1, thereby tricking our body into thinking we’re eating all the time. That’s how it dials down our hunger drive.
Ozempic for Weight Loss
In the longest trial to date, more than 17,000 individuals were randomized to injections of either high-dose semaglutide or placebo for four years. Overall, those 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. Even though they continued to get injected every week for three more years, they didn’t lose any more weight over the subsequent 143 weeks.
Weight loss tends to plateau because the same amount of effort to cut calories—whether through willpower, drugs, or surgery—is met with growing resistance as ongoing weight loss increasingly activates our feedback control circuit, stimulating our appetite. In the case of the GLP-1 drugs, the weight loss caused by the initial drop in appetite is undercut by an apparent exponential increase in caloric intake as our body ratchets up our hunger again. Within 12 months, this resistance, combined with the decreased caloric needs from being lighter, matches the persistent effort to cut calories, and weight loss plateaus. And, as soon as we stop taking the drugs, our full appetite resumes and we start regaining the weight we initially lost.
The Cost of Ozempic
Wegovy, the high-dose Ozempic used for weight loss, costs up to $1,350 a month, which, again, may have to be paid in perpetuity since any lost weight can pile back on if you stop taking it. So, that could cost more than $16,000 a year if paid out-of-pocket for those whose insurance doesn’t cover it.
Ozempic Side Effects
The most common side effects include nausea, vomiting, diarrhea, and constipation. Gallbladder issues are another side effect; excess cholesterol shed from fat cells can crystalize in our bile like rock candy, forming gallstones.
Rare but serious adverse effects are also emerging. The package inserts for both semaglutide and tirzepatide list a series of “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.
What Is “Ozempic Face”?
“Ozempic face” is a term used to describe a distorted facial appearance among users of the drug. (Similar accounts have been made of “Ozempic butt.”) Media reports have linked the drug with facial aging, but the sagging appearance has been ascribed simply to the accelerated loss of fat in the face. While this interpretation seems logical, a review of the phenomenon concluded that “this explanation cannot fully account for the markedly accelerated facial aging….” Other factors suspected as being responsible for the appearance of premature facial aging include the loss of facial muscle mass, diminished structural integrity of the skin, and changes in stem cell function and hormonal secretion.
Is Ozempic 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.
At this time, we don’t know about the long-term harms or benefits because some of these drugs and dosing schedules are so new. To complicate matters, the American Academy of Pediatrics has suggested offering these drugs for teens and even tweens as young as age 12. These drugs work by acting on the brain, so who knows what effect they might have on childhood development and beyond if young people end up taking them for the rest of their lives. Although we now have evidence of near-term benefit over a few years, we cannot assume long-term safety until it has been demonstrated.
Ozempic Alternatives
We don’t need to take GLP-1-mimicking drugs. Not only can the ingestion of a plant-based meal more than double GLP-1 secretion, compared to a meat meal, but plant-based diets can also cause weight loss by boosting our resting metabolic rate and incorporating “calorie-trapping” high-fiber foods that flush calories away. The largest study of people eating strictly plant-based found they are about 35 pounds lighter on average.
When we eat a donut, its fat, sugar, and starch get absorbed quickly, high up, before reaching the part of our digestive tract where we produce most of the hormone that suppresses our appetite, GLP-1. Since the cells that produce GLP-1 in response to calorie exposure are concentrated at the end of our digestive tract, while the majority of the calories we consume are absorbed early on, most calories never make it down far enough. That’s why our appetites aren’t suppressed very much these days. From a GLP-1 standpoint, when we have that donut, it’s like we never ate much of anything. No wonder we reach for donut number two.
Our prehistoric ancestors are believed to have consumed as much as 100 daily grams of fiber, which is more than six times what most of us are getting these days. We evolved eating massive amounts of whole plant foods—the only places fiber is found in abundance. That enabled out natural satiety mechanisms to keep us from overeating. By eating the way nature intended, we can release GLP-1 the way nature intended. That helps explains why in the medical literature, compared to any other way of eating that didn’t involve portion control, a whole food, plant-based diet has been shown to lead to greater average weight loss than any other diet.
For more in-depth information on Ozempic and GLP-1, check out these resources:
