What You Need to Know About GLP-1 Medications: Part 4

Over the last three blogs, we’ve explored GLP-1 medications in depth—from how the rise in obesity has driven their widespread use to how they work and why they’re so effective. While these drugs offer many benefits, they also come with significant downsides. This week, we’ll take a closer look at the potential risks and side effects.

Common Digestive Side Effects of GLP-1 Medications

Too much of a good thing can be bad.  When the desirable effects of GLP-1 drugs are over-expressed, side effects happen.  Slow down the digestive system just right and you feel fuller longer. Slow it down too much and you get nausea, vomiting, constipation and/or diarrhea. About 80% of people taking these medications will experience one or more of these undesirable digestive symptoms, predictably more so at higher doses. Rarely, GLP-1s can halt the movement of food through the digestive system altogether, causing obstruction – a medical emergency.

Fortunately for most GLP-1 users, the gastrointestinal side effects are mild to moderate in severity, generally tolerable and tend to improve with time, especially with careful and slow dose titration. Having said that, digestive issues are one of the main reasons people quit taking these drugs. 

Surgical Risks: Why GLP-1 Users Need to Be Cautious

Patients taking these medications also need to be aware that slowing down the digestive system can make it more dangerous to undergo surgical procedures. That’s because having residual food in the stomach can markedly increase the risk of perioperative complications – especially aspiration pneumonia. If you are undergoing an elective surgical procedure, chances are very high you will be asked to skip at least one dose of your GLP-1 medication. If you need emergency surgery (with no time to prepare), your surgical risk will be elevated simply based on the fact that you are taking a GLP-1 drug.

Dehydration and Kidney Risks

The reduced desire to eat and early satiety is accompanied by a decreased thirst signal, putting people taking GLP-1s at risk of experiencing dehydration. Prolonged or severe dehydration can lead to kidney damage.  So it’s important for patients using these medications to pay attention to fluid intake, drinking enough to produce relatively clear-looking urine.

Increased Risk of Gallstones and Pancreatitis

Patients taking GLP-1 medications are at higher risk of developing gallstones and gallbladder disease requiring surgery. And, although relatively rare, some people can develop pancreatitis, or inflammation of the pancreas. 

The pancreas is an organ deep in our abdomens, hidden behind the stomach. Besides making insulin, the pancreas makes various digestive enzymes that allow us to digest food, and delivers those enzymes to the intestinal tract via a series of channels. If the pancreas gets inflamed, the tissues around the channels can swell making it difficult for those digestive enzymes to get out, causing the pancreas to start digesting itself. 

As you might imagine, that would not only be a very painful condition but one that could be life threatening and warrant hospitalization, or even intensive care – and it is.  What’s more, that self-digestion causes scarring, making the channels permanently narrower, predisposing people to future pancreatitis attacks, thus setting up a vicious cycle. Pancreatitis may be rare, but (together with bowel obstruction) is probably the most dreaded side effect of GLP-1 medications. 

Link Between GLP-1 Drugs and Thyroid Cancer

There appears to be a slight increase in the incidence of thyroid cancer in GLP-1 users.  This is a rare form of cancer to begin with, so the increased risk of developing it is not much of a practical concern for most users.  But patients with a family history of endocrine tumors may want to take that into consideration when contemplating using these medications. Patients with a personal history of an endocrine-system cancer should avoid these drugs altogether.

Weighing the Risks vs. Benefits of GLP-1 Medications

These side effects can be scary – and if you experience any one of the more serious ones, they can be literally life altering. However, we have to put the most serious side effects in perspective. They are RARE. Meanwhile obesity is rampant and has its own downsides - which are not inconsequential. So, on balance, the side effects of using these drugs are felt to be outweighed by the side benefits of losing weight.  And as you've already learned, these drugs are very effective in making us eat less, and as a result are very effective at making us lose weight.

However, there is something that could actually be made WORSE by the weight loss itself. Weight loss that happens with calorie restriction alone is not selective. Meaning, people who go on GLP-1 drugs will lose not just fat mass but also muscle mass.  So unless you include regular exercise as part of your weight loss program, the weight you lose while taking Ozempic®, Wegovy®, Mounjaro® or Zepbound® will include both muscle and fat, but the weight you will regain after stopping the GLP-1 will be mostly fat, leaving you metabolically even worse off than when you started.

And there is one truth none of us can avoid: diet is the major driver of weight gain. And unless you change not only how much but also what you eat, you will never be able to get off of these drugs. As nearly all former GLP-1 users will attest, the weight just bounces right back. 

Bottom line, despite what all the ads or social media influencers might tell you, GLP-1 drugs are not an easy way out! GLP-1 use MUST be accompanied by a regular exercise program and major dietary change.

Which leads to an obvious question – why not just pursue major dietary change and regular exercise in the first place? We will discuss alternatives to GLP-1s in the next and final blog in this series.