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How new weight loss drugs affect your entire body

The positives and negatives of GLP-1 agonists

DETROIT – Medications like Wegovy, Zepbound and Saxenda are revolutionizing weight loss for millions of Americans, but they are relatively new to the medical landscape.

Related: Why is it so hard to find Ozempic in Metro Detroit? What can you do?

Large numbers of studies are being done to identify all of the risks and benefits of these medications, and so far, they appear to have far more benefits than risks. But I think a well-informed patient should be aware of both the benefits and risks in terms of what these medications do in your body.

The formal name for this class of medications is GLP-1 agonist. The medical names include semaglutide and tirzepatide. There are other similar medications that are also in the development pipeline.

To get a good idea of the scope of activity these drugs have, I interviewed eight different specialists to find out some specifics to each organ system.

How they work

According to Dr. Suki Singh, a Henry Ford health obesity medicine specialist, these medications work by decreasing the movement of food through your stomach. By slowing down digestion, you get fuller on a smaller portion of food and do not experience the same level of hunger.

“There is also a positive feedback to the brain which results in decreased food cravings, that ‘food noise,’ that common word we’re hearing on social media now, which again helps with decreasing that total calorie intake,” said Singh.

People should also understand that these medications are not meant to be taken forever. The goal is individualized to every patient depending on how much weight they need to lose. Ideally, they should be a temporary assist to help a patient lose weight as they implement diet and lifestyle changes that will be sustainable long-term off of these medications.

Beyond weight loss -- positives and negatives

There is no doubt that these drugs have a profound effect on the entire body. We can start simply with the brain and central nervous system. There is preliminary data, yet to be confirmed, suggesting there may be a beneficial effect regarding Alzheimer’s and Parkinson’s disease.

Working our way down, there is a clear benefit to the heart and cardiovascular system.

“People on GLP-1s are less likely to die from cardiovascular disease or for any cause, less likely to have a stroke, less likely to have a heart attack,” said Dr. Herb Aronow, a Henry Ford health cardiologist.

The drugs lower blood pressure and bad cholesterol, while raising the good cholesterol.

“I would say that in my career, the statins are probably one of the biggest blockbuster drugs we’ve seen, GLP-1s are poised to eclipse that, so this is really a major breakthrough for patients that have diabetes, or who are overweight or obese,” said Aronow.

Moving onto another organ system, the kidneys also appear to derive a great deal of benefit from GLP-1 use. Dr. Meaghan Roche, a Henry Ford health nephrologist explained, “What we’ve learned recently is that the GLP-1s actually do slow the rate of decline of kidney function. They reduce the amount of protein in the urine, and they reduce the number of people who die of kidney disease overall.”

One thing that could be considered a positive or negative is an effect on fertility. These medications do appear to improve fertility, according to Dr. Annmarie Vilkins, a Henry Ford health OB-GYN.

“It is biologically plausible that a GLP-1 agonist can improve your fertility by the indirect mechanism of decreasing your weight and improving ovulation,” said Vilkins. She notes though that the safety of GLP-1 medications while pregnant is not established and would recommend stopping them immediately if there is a pregnancy. It is certainly not recommended that patients use them in an attempt to conceive a child.

Vilkins also stressed that because some of the side effects of GLP-1 agonists include nausea and vomiting, it might reduce the effectiveness of contraceptive pills. People on these medications should take extra precautions to prevent pregnancy if they are experiencing nausea and vomiting.

While weight loss and the effects on the kidneys, brain and cardiovascular system are strongly positive, there is no doubt that there are also negatives to these medications, including gastrointestinal problems.

Dr. Brian Ginnebaugh, a Henry Ford Health gastroenterologist, said that up to 40 percent of patients experience nausea, and in many cases, it is severe enough that the GLP-1 agonist has to be stopped.

A related and concerning side effect is known as gastroparesis, meaning paralysis of the stomach.

The GLP-1 actually does inhibit gastric emptying, which means it slows down your stomach and when your stomach is more full and not processing food, the patient oftentimes has symptoms, nausea, vomiting, bloating, abdominal discomfort, and fullness,” said Ginnebaugh.

On a related note, Dr. Michael Lewis, chairman of anesthesiology at Henry Ford Health said that because the emptying of the stomach is slowed down significantly, if you are going to undergo any surgery or procedure where sedation may be necessary, it is important to discuss the situation with your doctor.

While there is no exact consensus at this point, it is strongly suggested that these medications be stopped prior to any procedure where a sedative might be given to prevent dangerous vomiting and the risk of aspiration of stomach contents.

Another concerning risk is the possibility of hypersensitivity reactions, as well as pancreatitis. Dr. Singh said those can be severe enough that a patient will no longer be able to take the GLP-1 agonist.

There are also nutritional side effects to these medications.

“One of the biggest side effects that come with these medications is a loss of lean muscle mass,” said Allegra Picano, a registered dietitian at Henry Ford Health.

Picano emphasized that eating adequate protein is important. Increasing fiber intake and taking a multivitamin are also beneficial since your dietary intake will decrease based on the way these drugs work.

Finally, Dr. Kathleen Estrada, a Henry Ford Health endocrinologist, wanted to remind people these weight loss medications started out as treatments for diabetes, so they can create blood sugar problems.

“A lot of people who are obese have insulin resistance, and so some of them may have what’s called reactive hypoglycemia, typically with large carb intake or carbohydrate intake,” said Estrada. “So if someone does have quite a bit of insulin resistance, focusing on a low carb diet can really help so they’re not spiking and then when the insulin finally does come out, they don’t have that subsequent drop that they feel.”

Final thoughts

My own thoughts after talking with all of these experts are that it’s important to remember that these are very effective medications, but you should only use them with the guidance of a specialist who can monitor you for problems and help you make the critical changes to your diet and lifestyle, so you can eventually successfully stop taking them.


About the Author
Frank McGeorge, MD headshot

Dr. McGeorge can be seen on Local 4 News helping Metro Detroiters with health concerns when he isn't helping save lives in the emergency room at Henry Ford Hospital.

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