Jorge Moreno, MD, specializes in treating obesity and obesity-related conditions.

The assistant professor of medicine (general medicine) at Yale School of Medicine is interested in helping prevent chronic disease. “I see all stages of it in primary care—before, during, and after complications happen,” he says. “In treating obesity, I'm often able to prevent or treat multiple conditions before complications arise.”

Moreno can relate to his patients’ struggles with weight: Having had obesity himself in college, he subsequently lost 50 pounds.

“My patients have gone through the world with a lot of stigma, bias, and blame, thinking obesity is their fault,” he says. “But we know that the body is working against them, and I can help them through that.”

In a Q&A, Moreno discusses the effectiveness of second-generation weight loss medications, their impact on other aspects of health, and how they change our relationship with food.

How do the novel weight loss medications differ from previous weight loss medications?

Medications for weight loss have existed since the 1950s. But the newer GLP-1 medications, which we call second-generation medications, are much more effective. Patients on these novel medications can achieve a 15% to 25% weight loss compared to 5% to 10% with first-generation oral medications.

The new medications fill a gap that wasn't addressed before 2021. Previously, with 5% to 10% weight loss, you could improve glucose control, blood pressure, fatty liver disease, and cholesterol numbers. But with 15% to 25% weight loss, you can reverse or put some of these conditions into remission.

For example, there's evidence that type 2 diabetes can be put into remission with this kind of weight loss. And I have many patients who have come off blood pressure medications using the newer weight loss medications. Our goal is not to lower BMI or the number on the scale—although those things will happen. Our goal is to improve health outcomes.

Why are these drugs so effective for weight loss?

We've learned that obesity is a complex condition with multiple neuroendocrine pathways in which the gut and brain affect how you eat and store fat. These medications are highly effective at decreasing appetite and resetting the patient's set point, the weight a body defends.

For example, if a patient who weighs 200 pounds loses 20 pounds, their hunger signals—their neuroendocrine hormones—are heightened, triggering appetite and causing the patient to go back up to 200 pounds. The body fights for the adiposity because it thinks you are starving yourself. The body wants that fat mass because fat is energy, and we need energy for our cells, brain, and heart to function.

Some doctors may tell patients to eat less or walk more. But that's an old paradigm. It’s not about willpower. We now know about the brain signals our patients are fighting and how biology works against us when we try to lose weight.

How do these weight loss medications help other health conditions, such as cardiovascular disease?

There are multiple ways that these medications may improve other health conditions.

Visceral fat, which overlies the liver, heart, pancreas, and other organs, has been shown to increase inflammation, which can lead to the development of insulin resistance, cardiac disease, and fatty liver disease, among other conditions. These medications are thought to decrease inflammation.

Patients have multiple complex conditions that are happening at once. There's diabetes, hypertension, high blood pressure, and sleep apnea. Many times, as doctors, we think of different conditions as silos. But if we treat obesity, it'll cascade down to treat all these other conditions.

Research has suggested there may be potential for these medications to benefit other conditions like depression, Alzheimer's disease, dementia, and Parkinson's disease. It is still very early, but the research is promising.

How do these medications change our relationship with food?

Many of my patients describe intrusive thoughts about food, often called food noise. They just had breakfast, and they're thinking about their next snack or lunch. If they plan to go to the movie theater after dinner, they’re already thinking about the popcorn. They're always thinking about when they’re going to have their next meal and what they’re going to eat. The thoughts can become almost anxiety-provoking.

Many of my patients who have always experienced food noise didn't know that it wasn't quote, unquote normal. But with the new anti-obesity medications, GLP-1s in particular, food noise appears to lessen. Regardless of how much weight they lose on these medications, patients feel more in control of their relationship with food because the brain’s food reward mechanisms quiet down.

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