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Sugars are sweet, tasty, and disastrous for your health in large quantities. They are also ubiquitous in modern society. We find them added to everything from salad dressings, drinks, bread, even peanut butter! Sugars and other carbohydrates make up over half of the calories consumed by Americans. Carbohydrates are broken down into a simple sugar called glucose and delivered around the body after eating. This can be surprisingly tricky. Too little glucose and cells can’t function. Too much and it gets converted to fat and damages the metabolic system, heart, and bloodstream. Type 1 Diabetes is a condition where the body doesn’t produce enough insulin. Type 2 Diabetes is more complicated; the body doesn’t respond to raised glucose in the bloodstream properly. A big culprit for failure is when insulin isn’t released well. To remedy this a class of drugs called glucagon-like peptide-1 (GLP-1) agonists have been developed.  Agonist in this case means the medication has a similar function to the natural hormone. The opposite is an antagonist, which acts in opposition to them. GLP-1 medicines include Trulicity, Mounjaro, and semaglutide / Ozempic. In this article, we will review how insulin works, how GLP-1 works on the cellular level, and what GLP-1 medicines do to the body.

Insulin is the main hormone that tells your body how to process sugar. Before we can understand how GLP-1 works, we need to understand the healthy release of insulin. This starts in the pancreas, an organ near our gut. The pancreas is filled with many types of cells called islet cells. These are responsible for regulating the balance of glucose in our bloodstream. Two major types are alpha and beta islet cells. Alpha islet cells produce glucagon and GLP-1. Glucagon tells the liver to increase blood sugar when you need energy. Beta cells make insulin and amylin, which help lower blood sugar. Alpha and beta islet cells work in opposition. They keep each other in check and our blood sugar levels just right. In Type 1 Diabetes, alpha cells may be dysfunctional and beta cells don’t exist or get destroyed. WIth Type 2 Diabetes, problems can occur when beta cells don’t function properly. Beta cells make insulin and release it in two stages. When these cells detect high blood glucose, they “trigger” and release insulin right away. This short response lasts 10-20 minutes, but is still several steps long. After triggering, a complicated “amplifying” pathway turns on to produce and release more insulin. Together this is powerful, slow, complex and has many potential points of failure. Beta cells are vital, and when they fail it often signals the transition from obesity to Type 2 Diabetes.

GLP-1 is like a shortcut for beta cells. When it is detected the triggering response is primed and the cells are ready to release insulin as soon as glucose is detected. This pathway bypasses a lot of the complicated cellular machinery that is damaged in diabetic patients. The upshot is that GLP-1 stimulates insulin release from islet cells. An added benefit is that the insulin is only released in the presence of elevated glucose. This is good because you don’t release too much insulin, which can be dangerous. GLP-1 medications also last much longer in the body than natural GLP-1, giving longer-term effects which can last for up to a day!

Now we know a little of how GLP-1 acts inside our cells, but what effects does this have on the body? Many, and widespread, it turns out! GLP-1 affects cells all over the body. The three biggest effects are decreased blood glucose, appetite suppression, and weight loss.

Insulin decreases blood glucose, and GLP-1 increases the response to glucose. But GLP-1 medications have a secret extra benefit. Remember that alpha and beta cells work opposite each other. Normally when blood sugar is low, we release GLP-1 from our pancreas along with glucagon. Glucagon is very useful, and one of its uses is to stimulate the liver into producing more blood sugar. GLP-1 medications suppress glucagon production and the liver stays quiet. The pancreas still releases insulin, but the liver produces 45% less glucose!

GLP-1 affects two of the biggest portions our appetite: our stomach and our brain. It slows the absorption of nutrients from the stomach, a process called gastroparesis. Food – and the glucose inside – is retained in the stomach and gut instead of the bloodstream. GLP-1 can also affect the brain. It can cross from the bloodstream into the brain, but also affect the vagus nerve – the major nerve connecting the brain and gut. Here it acts on the hypothalamus, suppressing the appetite and giving you feelings of being full. With the stomach slowing down and the brain signaling that it’s full, we tend to eat less.

Combined, lower blood sugar and appetite can have serious effects on weight. This can be a big benefit of GLP-1 medications. Weight loss is linked with better outcomes for Type 2 Diabetes patients. Getting to a healthy weight is also good for the heart, joints, liver, and so on. Significant weight loss has been seen with GLP-1. Let’s not sugar-coat this though; not all weight loss is created equal. Ideally we’d cut our body fat while maintaining – or building – our muscle. This is especially true with diabetes, as skeletal muscle uses up extra glucose. Unfortunately, when we lose weight through diet restriction we lose more than just fat. This is true of gastric surgery, diet-induced weight loss, and GLP-1 medications. In GLP-1 medication studies, 20-50% of the weight lost is things other than fat – including muscle. Studies vary widely. The type of GLP-1 medication and other medications patients are taking may affect this. The best way to offset this is through building muscle with exercise!

GLP-1 medications are truly amazing. They increase insulin response, lower blood glucose, suppress appetite, and lead to weight loss. It’s not all sugar and spice, however. Side effects can be rough, including vomiting and diarrhea. Additionally, meds can’t do it alone. When taking GLP-1 medications, the goal should still be to create an environment conducive to healthy living. Limiting carbohydrate intake is one critical step. Exercising is another. When fighting weight loss, victory is very sweet, but our diets shouldn’t be!

Written By Benton Lowey-Ball, BS Behavioral Neuroscience

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