How to Control the Side Effects (Including “Ozempic Face”) of GLP-1 Drugs

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How might we mitigate the gastrointestinal and muscle loss side effects of GLP-1 weight-loss drugs?

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Below is an approximation of this video’s audio content. To see any graphs, charts, graphics, images, and quotes to which Dr. Greger may be referring, watch the above video.

It appears the vast majority of people prescribed GLP-1 drugs stop taking them in a matter of months but compare that to older weight-loss drugs. Those had a 98 percent failure rate.

As I’ve mentioned, in drug trials, most people taking these types of weight-loss drugs started out obese and ended up obese, no matter how long they stayed on them––but that’s just on average. Some people, despite being on high-dose Ozempic for years, actually ended up heavier than when they started, and most remained overweight. But a small fraction of them, about one in 25, plateaued down at a normal weight. One in 25 doesn’t sound like a lot, but obese individuals are rarely able to achieve a normal weight. Without something drastic, like bariatric surgery, only one in 200 men with class 1 obesity, or one in 100 women, are able to find their way back to a normal weight. So, these drugs really can have a huge effect on a select few. Of course, you’d presumably have to stay on them forever to maintain that weight loss, at a cost of maybe $16,000 a year. But even for those who can afford the cost, the main reason they stop taking GLP-1 drugs is the gastrointestinal side-effect profile.

The most common side effects of Ozempic-type drugs include nausea, vomiting, diarrhea, and constipation. And they may also heighten the risk of pancreatitis, kidney failure, and thyroid cancer––but for now let’s stick to the common ones.

These significant adverse gastrointestinal effects were demonstrated in virtually every trial, though they weren’t bad enough to cause more than 15 percent of trial participants to drop out, and the vast majority of adverse effects got better after they stopped the drugs. Here are the numbers: 44 percent experienced nausea, 30 percent diarrhea, 24 percent vomiting, 24 percent constipation, and 20 percent abdominal pain. But 16 percent of those on the placebo injections experienced nausea or diarrhea too. So, it wasn’t all due to the drug. People don’t tend to just spontaneously vomit, though, so that’s more likely to be a drug-induced effect.

So, some people may not experience side effects at all, and these GI side effects have been shown likely to be dose-dependent, and more common during the dose escalation period. Thus, it’s recommended that these medications are started at lower doses and only increased as tolerated. So, starting low and going slow, gradually nudging up the dose over many months, can minimize some of these side effects. And in terms of what patients can do; eat slowly, smaller portions, eat a low-fat diet, small sips of fluid, get some fresh air, crackers, apples, mint, ginger, stay hydrated, avoid sports drinks, dairy products, coffee, alcohol, and soft drinks. Temporarily reduce your intake of fiber or increase it, depending on symptoms, and if things get really bad, avoid drinking during meals. If the symptoms persist or worsen, let your healthcare provider know ASAP.

One thing your doctor can do is prescribe anti-vomiting drugs to counter the side effects of the original drugs. But if you don’t feel nauseated all the time, will you still lose weight? Yes, even people who don’t feel sick to their stomach can experience the appetite suppression that leads to weight loss.

GLP-1 also makes you feel fuller for longer by slowing down the rate at which food leaves your stomach. That contributes to the nausea and vomiting, and can lead to a serious complication if you have to go under anesthesia for surgery. GLP-1 drugs slow your stomach down so much that the American Society of Anesthesiologists recommends people stop taking the drugs for up to a week prior to procedures so you don’t go under the knife with a full stomach, for fear that you’ll aspirate stomach contents into your lungs.

It turns out that one week may not even be long enough. Patients taking these drugs had a higher prevalence of increased residual gastric contents despite fasting, even if they stopped taking the drugs a week before. So, if you’re going in for elective surgery, consider stopping a drug like Ozempic at least three weeks before. Stopping these drugs for a month or so may not be tenable for diabetics using it to control their blood sugars, but if you’re just doing it for your weight, it’s a good idea to hold off.

GLP-1 type drugs like Ozempic function by making patients feel fuller, eat less, and, hence, lose weight. However, an important but often overlooked factor in studies of these kinds of drugs relates to the type of weight that’s lost.

Typically, when people who are obese lose weight, the decrease in their fat-free mass, meaning essentially their lean mass, including their muscles, usually represents about 25 percent of total weight loss. So, for every four pounds (2 kg) lost on the scale, one of those pounds isn’t fat. But on drugs like Ozempic, as much as 40 percent of the total weight lost is that lean mass––nearly half the pounds you’re losing. Those on Ozempic or Tirzepatide, a newer GLP-1 drug sold as Zepbound, lost about 14 pounds (6 kg) of lean mass––about one-eighth of all the lean mass in their body. That’s worse than the amount of lean mass you lose when you have esophageal cancer, or head and neck cancer.

Now, some people paid by the pharma companies that make GLP-1-type drugs question whether the amount of muscle mass loss is clinically relevant. But these drugs cause such rapid and significant loss of lean mass that it’s comparable to how much you’d lose over a decade or more of aging. The drug industry consultants argue that even if 40 percent of the weight lost is lean mass, that still means the majority—60 percent—is fat. So, you end up with a better fat-to-lean ratio in the end. But that’s just on the first go-around. Remember, most people don’t stick to these drugs for more than a few months, either because they can’t keep paying $1,000 a month for them, or they don’t want to put up with all the side effects, or deal with drug shortages, or run out of refills. And when you stop these drugs, we know the lost body fat piles back on, but there’s a concern that any lost muscle mass may not come back. So, you then actually end up fatter in the end.

This kind of weight cycling has been associated with extra fat deposition on the body, especially around the middle. Using the gold-standard method, MRI, to directly visualize muscle mass, researchers found that the more times people cycle their weight, the worse their body composition appears to get. The profound level of lean mass loss associated with GLP-1 weight-loss drugs would be expected to have deleterious impacts on health outcomes, including increased frailty and perhaps greater long-term mortality risk––though this concern remains theoretical, since any such long-term data have yet to be published.

The good news is there’s something we can do about it. Exercise, particularly resistance exercise, like weight training, can cut in half-or-more the proportion of fat-free mass that is lost. Check this out: based on half-a-dozen studies of caloric restriction for weight loss (like portion control), and the same calorie restriction plus resistance exercise, you can see that it appears the non-exercising group lost more weight. You can guess why, though, because without the resistance exercise, they lost more lean mass, whereas the exercising group lost nine pounds (4 kg), apparently without losing any lean mass.

Supervised resistance training interventions, up to a few times a week for more than 10 weeks, where all major muscle groups are worked, can add a few pounds of lean mass. More with weights than cardio, more when younger, and more in men than women. Collectively, this evidence supports resistance training as an effective approach to—at the very least—help mitigate the decrease in lean mass. So, programs such as these should be adopted without delay in patients embarking on Ozempic-type therapy.

What about “Ozempic face”? The term has consumed the media with the medication’s rising popularity, and describes rapid weight loss in the face that leaves a distorted appearance. And I’d never even heard of Ozempic butt. Media reports have linked the drug to facial aging, but perhaps it’s not so much the medication as much as the potent weight-loss effects that leave a sagging appearance due to the loss of fat in the face.

While this seems logical, the explanation cannot fully account for the markedly accelerated facial aging seen in GLP-1 drug patients. The premature facial aging and altered skin health appear to be multifactorial, involving not only the loss of fat in the face, but an effect on stem cells and the production and secretion of hormonal and metabolic factors. These changes compromise the structural integrity and barrier function of the skin, and may lead to diminished facial muscle mass as well, further exacerbating the appearance of aging.

Another side effect of rapid weight loss is gallstones, which is not limited to GLP-1 drugs. Shedding all that excess cholesterol stored in your fat cells can lead to it crystalizing in your bile like rock candy, forming gallstones. This is something else to be cognizant of, but in a way, both the muscle loss and gallstones may just be signs of how effective these drugs can be for losing weight. In my last video, I talked about the most common side effects, but as semaglutide’s popularity soars, rare but serious adverse effects are emerging. Like what about possible thyroid cancer, pancreatitis, kidney problems, depression, or suicidal thoughts? I’ll cover all those, next.

Please consider volunteering to help out on the site.

Motion graphics by Avo Media

Below is an approximation of this video’s audio content. To see any graphs, charts, graphics, images, and quotes to which Dr. Greger may be referring, watch the above video.

It appears the vast majority of people prescribed GLP-1 drugs stop taking them in a matter of months but compare that to older weight-loss drugs. Those had a 98 percent failure rate.

As I’ve mentioned, in drug trials, most people taking these types of weight-loss drugs started out obese and ended up obese, no matter how long they stayed on them––but that’s just on average. Some people, despite being on high-dose Ozempic for years, actually ended up heavier than when they started, and most remained overweight. But a small fraction of them, about one in 25, plateaued down at a normal weight. One in 25 doesn’t sound like a lot, but obese individuals are rarely able to achieve a normal weight. Without something drastic, like bariatric surgery, only one in 200 men with class 1 obesity, or one in 100 women, are able to find their way back to a normal weight. So, these drugs really can have a huge effect on a select few. Of course, you’d presumably have to stay on them forever to maintain that weight loss, at a cost of maybe $16,000 a year. But even for those who can afford the cost, the main reason they stop taking GLP-1 drugs is the gastrointestinal side-effect profile.

The most common side effects of Ozempic-type drugs include nausea, vomiting, diarrhea, and constipation. And they may also heighten the risk of pancreatitis, kidney failure, and thyroid cancer––but for now let’s stick to the common ones.

These significant adverse gastrointestinal effects were demonstrated in virtually every trial, though they weren’t bad enough to cause more than 15 percent of trial participants to drop out, and the vast majority of adverse effects got better after they stopped the drugs. Here are the numbers: 44 percent experienced nausea, 30 percent diarrhea, 24 percent vomiting, 24 percent constipation, and 20 percent abdominal pain. But 16 percent of those on the placebo injections experienced nausea or diarrhea too. So, it wasn’t all due to the drug. People don’t tend to just spontaneously vomit, though, so that’s more likely to be a drug-induced effect.

So, some people may not experience side effects at all, and these GI side effects have been shown likely to be dose-dependent, and more common during the dose escalation period. Thus, it’s recommended that these medications are started at lower doses and only increased as tolerated. So, starting low and going slow, gradually nudging up the dose over many months, can minimize some of these side effects. And in terms of what patients can do; eat slowly, smaller portions, eat a low-fat diet, small sips of fluid, get some fresh air, crackers, apples, mint, ginger, stay hydrated, avoid sports drinks, dairy products, coffee, alcohol, and soft drinks. Temporarily reduce your intake of fiber or increase it, depending on symptoms, and if things get really bad, avoid drinking during meals. If the symptoms persist or worsen, let your healthcare provider know ASAP.

One thing your doctor can do is prescribe anti-vomiting drugs to counter the side effects of the original drugs. But if you don’t feel nauseated all the time, will you still lose weight? Yes, even people who don’t feel sick to their stomach can experience the appetite suppression that leads to weight loss.

GLP-1 also makes you feel fuller for longer by slowing down the rate at which food leaves your stomach. That contributes to the nausea and vomiting, and can lead to a serious complication if you have to go under anesthesia for surgery. GLP-1 drugs slow your stomach down so much that the American Society of Anesthesiologists recommends people stop taking the drugs for up to a week prior to procedures so you don’t go under the knife with a full stomach, for fear that you’ll aspirate stomach contents into your lungs.

It turns out that one week may not even be long enough. Patients taking these drugs had a higher prevalence of increased residual gastric contents despite fasting, even if they stopped taking the drugs a week before. So, if you’re going in for elective surgery, consider stopping a drug like Ozempic at least three weeks before. Stopping these drugs for a month or so may not be tenable for diabetics using it to control their blood sugars, but if you’re just doing it for your weight, it’s a good idea to hold off.

GLP-1 type drugs like Ozempic function by making patients feel fuller, eat less, and, hence, lose weight. However, an important but often overlooked factor in studies of these kinds of drugs relates to the type of weight that’s lost.

Typically, when people who are obese lose weight, the decrease in their fat-free mass, meaning essentially their lean mass, including their muscles, usually represents about 25 percent of total weight loss. So, for every four pounds (2 kg) lost on the scale, one of those pounds isn’t fat. But on drugs like Ozempic, as much as 40 percent of the total weight lost is that lean mass––nearly half the pounds you’re losing. Those on Ozempic or Tirzepatide, a newer GLP-1 drug sold as Zepbound, lost about 14 pounds (6 kg) of lean mass––about one-eighth of all the lean mass in their body. That’s worse than the amount of lean mass you lose when you have esophageal cancer, or head and neck cancer.

Now, some people paid by the pharma companies that make GLP-1-type drugs question whether the amount of muscle mass loss is clinically relevant. But these drugs cause such rapid and significant loss of lean mass that it’s comparable to how much you’d lose over a decade or more of aging. The drug industry consultants argue that even if 40 percent of the weight lost is lean mass, that still means the majority—60 percent—is fat. So, you end up with a better fat-to-lean ratio in the end. But that’s just on the first go-around. Remember, most people don’t stick to these drugs for more than a few months, either because they can’t keep paying $1,000 a month for them, or they don’t want to put up with all the side effects, or deal with drug shortages, or run out of refills. And when you stop these drugs, we know the lost body fat piles back on, but there’s a concern that any lost muscle mass may not come back. So, you then actually end up fatter in the end.

This kind of weight cycling has been associated with extra fat deposition on the body, especially around the middle. Using the gold-standard method, MRI, to directly visualize muscle mass, researchers found that the more times people cycle their weight, the worse their body composition appears to get. The profound level of lean mass loss associated with GLP-1 weight-loss drugs would be expected to have deleterious impacts on health outcomes, including increased frailty and perhaps greater long-term mortality risk––though this concern remains theoretical, since any such long-term data have yet to be published.

The good news is there’s something we can do about it. Exercise, particularly resistance exercise, like weight training, can cut in half-or-more the proportion of fat-free mass that is lost. Check this out: based on half-a-dozen studies of caloric restriction for weight loss (like portion control), and the same calorie restriction plus resistance exercise, you can see that it appears the non-exercising group lost more weight. You can guess why, though, because without the resistance exercise, they lost more lean mass, whereas the exercising group lost nine pounds (4 kg), apparently without losing any lean mass.

Supervised resistance training interventions, up to a few times a week for more than 10 weeks, where all major muscle groups are worked, can add a few pounds of lean mass. More with weights than cardio, more when younger, and more in men than women. Collectively, this evidence supports resistance training as an effective approach to—at the very least—help mitigate the decrease in lean mass. So, programs such as these should be adopted without delay in patients embarking on Ozempic-type therapy.

What about “Ozempic face”? The term has consumed the media with the medication’s rising popularity, and describes rapid weight loss in the face that leaves a distorted appearance. And I’d never even heard of Ozempic butt. Media reports have linked the drug to facial aging, but perhaps it’s not so much the medication as much as the potent weight-loss effects that leave a sagging appearance due to the loss of fat in the face.

While this seems logical, the explanation cannot fully account for the markedly accelerated facial aging seen in GLP-1 drug patients. The premature facial aging and altered skin health appear to be multifactorial, involving not only the loss of fat in the face, but an effect on stem cells and the production and secretion of hormonal and metabolic factors. These changes compromise the structural integrity and barrier function of the skin, and may lead to diminished facial muscle mass as well, further exacerbating the appearance of aging.

Another side effect of rapid weight loss is gallstones, which is not limited to GLP-1 drugs. Shedding all that excess cholesterol stored in your fat cells can lead to it crystalizing in your bile like rock candy, forming gallstones. This is something else to be cognizant of, but in a way, both the muscle loss and gallstones may just be signs of how effective these drugs can be for losing weight. In my last video, I talked about the most common side effects, but as semaglutide’s popularity soars, rare but serious adverse effects are emerging. Like what about possible thyroid cancer, pancreatitis, kidney problems, depression, or suicidal thoughts? I’ll cover all those, next.

Please consider volunteering to help out on the site.

Motion graphics by Avo Media

Doctor's Note

This is the third video in my series on Ozempic. If you missed the previous ones, check out GLP-1 Weight-Loss Drugs Like Ozempic (Semaglutide): How Do They Work? Are They Effective? and Why Do Most Users Quit Ozempic and What Happens When You Stop?. Stay tuned for the rest of the series, including: 

Don’t want to wait? Get my new book, OZEMPIC: Risks, Benefits, and Natural Alternatives to GLP-1 Weight-Loss Drugs, available as an ebook, audiobook, and softcover (currently on sale for 20% off) 

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