Taming Hunger

The gut-brain pathway

Although the topic of tonight’s dinner is medication management for weight, says Collins, we should remember that the foundation of any medical condition is understanding one’s health behaviors. What are someone’s eating habits? What is their physical activity? 

“Let’s consider how to move our bodies more, how to have restorative sleep, how to avoid risky substances, how to increase social connection and reduce stress,” she says. “All these are a crucial part of therapy.”

“Does taking these medications mean I’m enjoying food less?” asks a panelist.

“Great question,” says Anugu. “Let’s talk about the physiology and pathophysiology. Weight is so complex. It is not just about what you’re eating and how you’re moving your body, it is also about hormones, genetics, dysregulation related to sleep, stress, etc.”

There’s a pathway in your brain that tells you you’re full, and it gets signals from your GI tract and adipose tissue, she says. “But we still eat even when we’re full, right? So that’s more related to the reward-pleasure system. While these drugs increase satiety signals to the brain, they seem to eliminate these emotional or stress cravings as well. People feel like the ‘food noise’ stops and they are less interested in food.”

The next thing the new weight management drugs do are to slow down your GI tract. “When you eat something small, you feel full. This can result in side effects: if things are moving slowly, you’re more likely to get constipated. You’re also more likely, if you overeat, to make yourself nauseous.”

“And how does the drug trigger an insulin response?” continues the panelist.

“GLP-1 agonists like semaglutides do increase insulin secretion in response to glucose in the bloodstream,” says Collins.    

Insulin is the hormone that allows sugar inside a person’s cells as energy. If the person doesn’t need the energy, it can be turned into fat cells. 

“So if you grew up eating, say, a carbohydrate-heavy diet and have insulin resistance, it’s much harder to lose weight,” Anugu says. 

“It’s a cumulative effect,” adds Collins. 

Miracle drugs?

“Do we just need to give everyone who is overweight semaglutides and they won’t have a problem anymore?” asks a panelist.

“We see patients who have struggled with weight for a long time and once they start seeing results with medication management, they become more invested in nutrition, physical activity, stress reduction, getting better sleep,” says Anugu. “Those actions are also helping their gut.”

“Why did these medications just burst onto the scene?” asks another panelist. 

“I was prescribing similar drugs, like Trulicity, when I was a resident,” says Collins. “We saw some weight loss with the earlier medications but not nearly to the degree we do with the newer ones. And tirzepatide (Zepbound/Mounjaro) really changed things, because some people are losing weight in ranges similar to those who complete bariatric surgery.”

Anugu says the amount of medication-assisted total body weight loss went from 5-8% with the older FDA-approved drugs to 12-18% with semaglutide, then to 20-28% with tirzepatide. Recent studies have shown even higher weight loss for patients who have been on the drugs for more than a year. 

“This is why it’s shaken the landscape of how we treat obesity,” Anugu says. “But here’s the thing: this medication works when you take it, but typically if people stop taking it, they tend to regain a significant amount of weight.”

“Why are they so expensive?” asks a panelist, who says she takes a compounding pharmacy version due to cost. 

Indeed, the average retail cost of a 28-day supply of an FDA-approved semaglutide is about $1,000. Some insurance companies cover semaglutides for both diabetes and weight loss.  Medicaid largely covers the drugs when used for type 2 diabetes, but coverage for weight loss is limited.

Semaglutides from compounding pharmacies, which are not FDA-approved, have become popular because they are much less costly. But both physicians say they would strongly recommend not using generic semaglutides from compounding pharmacies because quality, safety, and effectiveness cannot be guaranteed. (Compounding of medications is only allowed when the medication is on the FDA short supply drug list.) 

“That’s why Emory officially says, we do not recommend you get these from compounding pharmacies,” Collins says. “You don’t know what you’re getting.

“Semaglutides are so expensive to the system,” continues Collins. “We’re trying to figure out how to continue to provide this benefit but not break the system. And that’s a question that every insurance company is trying to answer.

“The problem is, these are not one-time medications,” she says. “These are medicines you would likely need to take for a significant period of time.” 

Additional benefits

“But aren’t you then getting a cost savings in diabetes medication and all the other medicines for comorbidities?” asks a panelist. 

GLP-1s are clearly beneficial medications, say the doctors. A host of health benefits have been linked to the drugs beyond treatment for type 2 diabetes and weight loss. “Studies are coming out showing how these medications are helping individuals with kidney disease, sleep apnea, a history of cirrhosis, cardiovascular disease,”
says Anugu. 

Indeed, multiple studies are also in progress to determine if semaglutides are helpful for Alzheimer’s disease, Parkinson’s, polycystic ovary syndrome (PCOS), alcohol use disorder, and many other ailments. 

It appears some of these benefits stem not only from weight loss but from GLP-1 receptor agonists stimulating the body to release insulin appropriately, reducing the impact of sugar. 

“If you’re on semaglutides for a while, do you reset your insulin to where it kind of rebounds and does the job better or do we know yet?” asks a panelist. 

“Absolutely, you can reset and improve your insulin sensitivity and responsiveness,” says Collins. In fact, we adjust our insulin responsiveness daily, depending on what and when we eat. 

“Is there a way to determine my ‘natural weight?’ ” the panelist continues. “To find out if I’m just fighting against where my body wants to be?”

“There’s this concept of your ‘set point’ in the literature, and it theorizes that the weight you’ve been most of your life is your homeostasis, and your hormones are in balance at this level,” says Anugu. “So if you lose weight
below that point, your body will make it harder to maintain that weight loss, and vice versa. 

“There are some markers in the labs that endocrinologists or specialists could order, like fasting insulin levels and body composition, or percent of visceral fat (beneath the abdominal wall muscles) vs. subcutaneous fat (just beneath the skin).”

When not to use 

Some contraindications exist for GLP-1s: They are not recommended for children under 18, people who are pregnant or nursing or who have type 1 diabetes, diabetic ketoacidosis, a history of pancreatitis, multiple endocrine neoplasia (MEN syndrome), or a specific type of thyroid cancer. 

People on semaglutides are often asked to discontinue them for a period of time before surgery, as the slowing of digestion can cause an increased risk of aspiration under anesthesia.

GLP-1s also should not be seen as a golden ticket, but as one tool in the kit of supporting a healthy lifestyle. “It’s still important to look at the underlying factors causing weight gain,” says Collins, “which could be nighttime eating or feelings of depression. If you target these causes, you’re more likely to have weight loss.”

If depression is present, medications like Wellbutrin (which can decrease appetite) and therapy can be game-changers, they say. 

“We’re all fixating on these injection medications, but it’s
not just one medicine fits all,”
says Collins.

High-fiber foods are “nature’s way of triggering these receptors,” she adds. “That’s why eating plants is really important.”

Taking GLP-1s

“How do you know when you’re on the right level of the medication?” asks a panelist currently taking a semaglutide. 

“I think what’s safe is 0.5 to two pounds of weight loss per week and making sure you’re still eating. You shouldn’t feel so full or nauseous that you’re not eating enough. This is crucial,” Anugu says. 

Frequent check-ins are important, since some people are “hyperresponders” who lose too much weight too quickly.

 “Everyone is different,” says Collins. “I evaluate how much weight people are losing and how they’re feeling. Are they still eating foods that provide their essential macro- and micronutrients? Based on that, we decide whether to escalate or not.”

“And what about drinking fluids?” asks a panelist. 

“Yes, you have to drink water, eat protein—some people supplement with protein shakes— and do weight-bearing exercises/strength training because you will lose muscle mass, and that affects your metabolism and your risk for osteoporosis,” says Collins.

“How long before people start to plateau?” asks a panelist. 

“That is variable. Some people plateau within 10 to 18 months,” Anugu says. “Sometimes that’s a signal to go up on the medication, if they’re still at a weight they’re not comfortable at and that’s still putting them at risk. As long as they can tolerate a higher dose.”  

“When do you move to maintenance levels or wean patients off the medication?” the panelist continues. 

“I don’t just look at someone’s weight or BMI. That doesn’t tell you the whole story,” says Collins. “Ideally we would look at lean body mass, how they are feeling, and other indicators.” 

“What about switching from one medication to another?” asks a panelist considering transitioning from Ozempic to Mounjaro.

“Mounjaro is more effective for weight loss,” Anugu says. “But in terms of good side effects—meaning decreased rates of chronic disease—we are seeing that across the board.” 

“Remember that it’s important to work with a provider who knows about weight and nutrition and can help you take steps toward creating a healthy lifestyle beyond just taking a specific medication,” Collins says. “The practice of medicine is still an art, not only a science.” EHD

By Mary Loftus • Photos Jack Kearse • Illustrations by Aad Goudappel • Design by Peta Westmaas