GLP-1 medications (such as Ozempic®, Wegovy®, Mounjaro®, and Zepbound®) have been making headlines—and for good reason. These innovative treatments have transformed the way we manage certain health conditions, particularly obesity. But as with any breakthrough therapy, there’s a lot to unpack.
Benefits of GLP-1 Medications
GLP-1 agonists were first approved for treatment of type 2 diabetes in 2005. And they are effective in helping to manage this condition, significantly improving blood sugar levels in a relatively short period of time. This makes sense given that GLP-1 has multiple effects on our biochemistries that culminate in the reduction of circulating glucose levels.
Since that time, GP-1s have gained FDA approval for the treatment of cardiovascular disease, obesity, sleep apnea and kidney disease. Emerging data suggest that this class of medications may even have roles in other—somewhat unrelated—conditions.
The Downstream Benefits of Weight Loss
One big reason that GLP-1s have positive effects on a whole host of health conditions is that obesity is a major driver of what ails us! And GLP-1s most definitely help people lose weight. So, for example, it’s not surprising that sleep apnea or fatty liver disease is helped by these medications – after all, weight loss can reverse both in a large proportion of patients. So ANY condition that is positively impacted by weight reduction will be positively impacted by GLP-1s.
But all the benefits do not emanate from weight loss alone. What we’re discovering is that GLP-1 receptors are not just present in the brain, gut and pancreas. They’re present all over.
Benefits of GLP-1s Beyond Weight Loss: Cardiovascular Disease
They are present in the kidney and, as it happens, are important to regulating blood pressure levels. GLP-1 receptors are also present in atherosclerotic plaque. Stimulating those helps reduce inflammation and thus promotes plaque stability. Put the BP lowering and plaque stabilizing effects together and you have a medication that helps prevent heart attacks and strokes – especially in those with established heart disease (who are at highest risk for additional cardiovascular events). It’s only a matter of time before treatment guidelines tell us to put every patient with established heart disease on Ozempic®.
Benefits of GLP-1s Beyond Weight Loss: Neurodegenerative and Joint Disorders
There’s even interesting data emerging around neurodegenerative conditions such as Parkinson’s and Alzheimer’s disease. We already know that GLP-1 receptors are present in the brain. What we’re finding is that the same anti-inflammatory effects that can help stabilize plaque can also reduce inflammation in the brain and reduce the likelihood of developing one of these conditions.
Animal trials testing injecting GLP-1 drugs into arthritic joints have also been undertaken. And so far, the results are promising. The anti-inflammatory properties of these drugs could open another line of therapeutics for osteoarthritis, the most common joint disorder affecting people as they age.
Benefits of GLP-1s Beyond Weight Loss: Addiction and Chemical Dependency
What’s more, these drugs even have an impact on addictive behaviors. The GLP-1 mediated signaling in the brain that makes us less hungry and less interested in food, makes us less compulsive - not just about eating but about a lot of different things. Like alcohol use and gambling. Not necessarily providing a cure for alcohol-use disorder or compulsive gambling. But representing a potential tool in the tool box for helping treat these self-destructive disorders.
All good. No – great, actually. Miracle drugs transforming disease care.
Apparently, there is nothing these medications can’t do! Or conditions they could be approved for. I’m pretty sure neither Novo Nordisk (the company behind Ozempic® and Wegovy®) or Eli Lilly (the manufacturer of Mounjaro® and Zepbound®) would object to all of us having at least one indication for taking these drugs.
While these drugs offer many benefits, they also come with significant downsides.
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?
Stop Interfering with GLP-1 Production
We can boost GLP-1 levels naturally by either adding in foods that increase production - or by getting rid of substances that blunt it.
The most obvious first thing to do is eliminate those substances that could be reducing GLP-1 levels. And one thing we know for certain is that GLP-1 production can be blunted by non-nutritive sweeteners. So, ditch the diet sodas (actually all sodas!). And be wary of foods touting themselves as “low sugar” as they’re often loaded with non-nutritive sweeteners.
And then work hard to boost GLP-1 production.
Boost GLP-1 Levels with Food
All food can stimulate GLP-1 release. It’s just that the cells that produce this appetite-suppressing hormone are concentrated all the way at the end of our digestive tract, meaning food has to make it there to have the biggest effect. It therefore goes without saying that if we eat food that is easily digested and rapidly absorbed (i.e. highly processed items), we will be missing out on our full GLP-1 manufacturing potential. So reducing intake of processed foods and favoring fiber-rich items instead should be the goal.
Fiber slows digestion while improving intestinal transit, helping get food to where the GLP-1 is being produced. Once there, gut bacteria break down the fiber found in fruit, vegetables and whole grains into short-chain fatty acids. Those fatty acids then signal cells in the intestinal tract to release GLP-1 into the bloodstream.
So if we want to increase the amount of GLP-1 our body produces naturally, we must up our fiber intake. But not by a little. By a lot. Adding around 10 grams of prebiotic fiber is what’s required to make a real difference in GLP-1 production. (Conveniently, that’s what 2 servings of Step One Foods delivers). After even 3 days of regular high fiber dietary consumption, studies have shown that GLP-1 levels can go up by as much as 56%. These levels continue to rise further as people stick with a high fiber eating plan for the long haul - probably because consuming fiber consistently encourages the growth of gut bacteria that thrive on breaking it down.
The Best Dietary Advice Ever
Which leads us to losing weight and keeping it off without stress or using drugs. For that we need to revisit the best dietary advice I’ve ever come across. It’s all of 7 words long and comes from Michael Pollan. And although it was coined nearly 20 years ago, it's still relevant, perhaps even more so, in the era of GLP-1s:
“Eat food. Not too much. Mostly plants.”
“Eat food” is the only part that requires a bit of explanation. When Michael Pollan talks about “food” he means REAL food. Food that our great grandmother would recognize as food. She would not recognize 80% of the items found in a standard grocery store today. She would certainly not recognize anything containing non-nutritive/artificial sweeteners!
The beauty of this dietary dictum is that not only is it easy to understand and follow, it automatically eliminates items that could be interfering with weight loss and GLP-1 production - while also automatically encouraging intake of foods that naturally boost GLP-1 levels and health overall.
The other benefit of following this dietary advice is that it leads us to consume fewer calories without having to think about it. If we are eating lots of plant-based foods in their most whole and unprocessed forms, we are filling our stomachs with items that are not only fiber and nutrient rich - but also calorie poor. Meaning we can eat relatively large volumes of naturally satiating foods while painlessly achieving lower calorie intake.
Add some exercise, and we have some serious calorie deficits happening. A daily 2 mile walk, representing about 30 minutes of moderate intensity exercise, results in 200 calories being burned. Trade out the 8 ounce steak for a cup of beans and save another 400 calories.
This path may be harder than weekly injections - at least at the start. And the weight loss achieved with diet and exercise might not happen as quickly as it would with GLP-1 medications. But this approach will absolutely afford better overall health, help avoid medication side effects, and offer us a real chance for achieving long-term success.