Weight Loss: The Least Interesting Thing About GLP-1s

By Irene Yeh

At last month’s Integrative Healthcare Symposium, GLP-1s were one of the main topics, especially regarding their impact on weight loss and obesity treatment. But for Monique Class, co-founder of The Center for Functional Medicine and The Institute for Functional Nursing, GLP-1s are more than just weight loss drugs. During her presentation, she proposed that GLP-1s can be used as metabolic, neurobehavioral, and anti-inflammatory tools that can catalyze sustainable changes when used strategically—specifically, through microdosing. 

“The most uninteresting thing about this medication is that you lose weight,” said Class. “The most interesting thing is its global impact on the system.”  

Not everyone should be on GLP-1s, and some people need to be on them forever, explained Class. And for others, low doses that will reverse physiology, provide them opportunities to make the right decisions, and invigorate their own endogenous GLP-1s are the right way to go, with an end goal of reverse engineering their systems and eventually getting them off.  

Mitochondria is the Powerhouse 

It’s a common story. Patients who struggle with weight loss have tried various methods to lose weight. Yet many of them are stuck. These patients feel discouraged and fall back on old habits, resulting in them staying at their current weight or regaining weight. To overcome this, patients need the right tools to empower and educate themselves on what they can do to create metabolic balance.  

“The system wants to be in balance,” said Class. The body uses carbohydrates and glucose as the easiest source of energy, but it can also burn fatty acids for fuel when carbohydrates aren’t available. Metabolic flexibility is the key. 

At the center of creating metabolic flexibility are the mitochondria, which take broken down proteins, carbohydrates, and fat and convert them into energy for the body. The strategy is to provoke the mitochondria to start burning instead of storing energy. To get the mitochondria to convert macronutrients into energy, it requires a little bit of inflammation and oxidative stress to drive the system. But too much inhibits the system. Eating several times a day is one way to drive up inflammation and oxidative stress. The average American has about 11 eating events per day. 

This is where GLP-1 drugs can give support. When prescribed at low doses, these drugs can offer the patient a moment of hesitation and an opportunity to choose not to eat or drink something, preventing inflammation and oxidative stress. However, Class cautioned against getting swept up in the excitement of the appetite suppression, as that also has its own detrimental side effects. 

“[Patients] think they should have no appetite whatsoever,” commented Class. “That’s bad news; that’s bad medicine. They’re wasting their muscle mass creating all of these metabolic adaptions that keep them stuck on these drugs.” 

GLP-1s also have an anti-inflammatory effect. Class cited her own experiences with her clients. Those who were prescribed even just one milligram experienced anti-inflammatory benefits, such as reduced joint pain. Small doses also decrease inflammation in the brain, resulting in improved depression, though Class also warns the opposite effect occurs. Some clients reported increased anxiety due to decreased levels of blood sugar and the patient not eating enough to get their blood sugar to a balanced level. 

Lowering Food Noise, But Not Completely 

GLP-1 drugs are often touted as completely removing food noise. However, Class discouraged the idea of totally erasing food noise. Rather, it must be lowered. Otherwise, patients could fall back to old habits and into the trap of yo-yo dieting.  

“Turning off the food noise is not what you want to do,” she said. “You want to lower the food noise so that people cannot be so starving and so driven by the ebbs and flow of their insulin and glucose that they create a vicious cycle.”  

Furthermore, reducing food noise gives patients a second to pause and make intentional choices. It gives them agency and moves them from compulsion to consciousness, putting their health back under their control.  

This applies to addiction, as well. Class recalled how one of the first things she noticed was her clients no longer had a desire to drink alcohol. Even though she initially was reluctant to prescribe GLP-1s, she realized that providing her clients with small amounts helped them stop consuming alcohol and sugar.  

Lifestyle Still Matters 

Like most drugs, GLP-1s should not be used as a cure-all. They are tools that can help patients get to where they need to be. Lifestyle interventions, at the end of the day, make up the bulk of sustainable weight loss. These interventions include diet, gut microbiome, exercise, and timed eating, which are positioned as mechanisms to stimulate endogenous GLP-1 production and restore mitochondrial function. 

Diet is obviously a key lifestyle asset. In the body, L cells—the backbone of endogenous GLP-1s—in the gut interact with food that enters the body. The microbiome stimulates the L cells of the gut. As such, maintaining a healthy gut microbiome will allow better interactions. “When you look at what stimulates our own endogenous GLP-1, it’s protein … it’s fiber and fermented foods.” 

Class explained that consuming even a forkful of fermented foods, including kimchi and sauerkraut, can fundamentally change the gut microbiome that can stimulate short chain fatty acids that stimulate the differentiation of the L cells that help the body make its own endogenous GLP-1s. She also recommended a modified Mediterranean diet—focusing on whole foods, fiber, lean proteins, and healthy fats. Carbohydrates should also be ideally consumed in the morning. This is because endogenous GLP-1 levels are highest in the mornings and lowest at night. Consuming carbohydrates—or meals, in general—at night will cause the body to store it and not metabolize it the same way compared to during the day, thus building up body fat.   

GLP-1 drugs also do not address nutrition gaps. Patients may actually be further deprived of nutrients due to lessened appetites caused by GLP-1s. Class recommended multivitamins if needed and Vitamin D, which is a hormone signaling molecule. She highlighted the importance of fish oils, or omega-3 fatty acids. The anti-inflammatory effects of fish oils make cell membranes become more fluid and flexible, allowing insulin and hormones to bind better. Protein can also help with brain fog and fatigue. Five grams of creatine, for example, offers a phosphate group that can rapidly convert ADP to ATP. 

“The only side effect I’ve seen is sometimes [patients] can get GI distress from it. But it helps mop up inflammation [and supply] soluble fiber for the short chain fatty acids,” noted Class. 

Time-restricted eating, or fasting, increases endogenous GLP-1s, and having it start at night is ideal. Class noted that not all fasting is created equally and that it is different for each patient. But there are many different fasting styles and patterns that can be offered. This includes intermittent fasting (e.g. 12-12-hour, 14-10-hour, 16-8 hour windows), as well as prolonged fasting of up to 48 hours. Fasting allows cellular cleanup of broken DNA and other debris, essentially cleansing the body, and increases endogenous GLP-1.  

“If you’re going for cellular cleanup, you don’t start here with somebody that’s metabolically crazy. You start there once they’re stable,” Class noted.  

Exercise also plays a big role. All exercise, even light exercise, increases mitochondria biogenesis. “Sitting is the new smoking,” as Class put it. Even if people exercise for half an hour per day, if they are sedentary for the rest of the day, then that does not allow the body to metabolize and begin mitochondria biogenesis. 

Small movements and being consistent with them are a good place to start, such as getting up every hour to take a walk around the house or do some chores. The key, according to Class, is to get patients moving through “tiny things” and “little pulse movements” throughout the day. Other forms of exercise also include resistance training and high-intensity interval training (HIIT) generate mitochondria biogenesis. However, HIIT exercises can also cause more inflammation and oxidative stress, so they won’t be suitable for everybody, especially patients that have complex chronic diseases. It is possible to metabolically overtrain certain patients and make them sicker.  

GLP-1 drugs are not meant to be a weight loss-only, cure-all medicine, but they can be used as a bridge for patients to achieve their health goals. “People don’t lack motivation; they lack a really good plan,” said Class. “These medications have the ability to reset both mindset and physiology, and that’s the ultimate of sustainable change.”