5 Questions on Weight-Loss Meds: Expert Q&A

Holly Lofton, MD, is an obesity medicine specialist and the director of the medical weight management program at New York University Langone Health. Here, she answers key questions about what it’s really like to take obesity medication – and why it’s not the first thing she turns to.

“If a patient comes to me and they say, ‘I've never tried any diet, but I want medication.’ I say, ‘Try a diet and come back, and then we'll see if you need medications, because they can really optimize the outcomes,’” Lofton says. “Nutrition and exercise should always be part of the plan, whether it’s for weight loss or weight maintenance.”

But many people have tried that – only to have pounds lost boomerang back. Here’s what Lofton says you should keep in mind if you’re considering trying medication.

Holly Lofton, MD: The goal of weight loss in the medical setting is fat loss. We don't want to lose water, or hair, or bone. 

So the way to think about it is, by how much percentage is my fat content decreasing? 

Now, it's hard to quantify that without some sophisticated and expensive equipment. So we use the scale because it's easier and convenient. 

But ultimately the goal is to decrease fat mass and maintain muscle mass. 

Lofton: Obesity is a heterogeneous condition: My obesity is not the same as your obesity, or another 20 people's obesity. That's why we can't say, “These people are going to do better.” 

We do tend to see that the first attempt you make at doing something, you will get more results. And there are people who we call our “super responders.” There's research being done to try to find out what it is about those super responders that makes them that way. 

But right now, there are really no predictive measures that we know of.

Lofton: In general, usually we see weight regain [after stopping medication]. That's because weight management is a chronic condition. 

Fat cells shrink, to a degree, when we diet and exercise, and then they don't shrink anymore. That's why we use the medication. 

When someone loses weight with, let's say a GLP-1, we tend to see around 20% weight loss while they're on the medication. When that medication is withheld, we see 50% to 70% of that weight regained over about six to eight months because the medication is gone. That's pretty much across the board for any medication. 

Not to say that some people won't lose and keep it off, but on average we see weight regain with discontinuation of medication. 

Clinically, I've seen both. I've seen people not take the medication after a while and gain no weight. I've seen people stop the medication and gain everything back, even when doing the best with their lifestyle. It's extremely variable. 

They're working on better medications that you can take maybe once a month, but right now, we're not there.

Lofton: There have been many studies looking at an analysis of people taking weight loss drugs. A study on Zepbound found that in both the drug group and the placebo (lifestyle) group, they lost 75% fat and 25% muscle. So the drug didn’t increase muscle mass loss. 

There are ways to minimize muscle loss: eating protein, working out, and building your muscle. Keeping your muscle mass helps you maintain your metabolism, which can bode well for maintenance.

I usually tell patients that when you're halfway to your weight goal, if you haven't started already, you need to increase your muscle-building activity. 

There are grip strength tests to determine if you're getting weaker. Less reliably, you can do caliper testing, but this depends on the expertise of the person doing the test. 

An inexpensive way to look at potential muscle mass change is to note how many squats you can do over time. If you started off with two squats and now you can do 10, you're getting stronger. If you could do 10 squats, and now you can only do two, you're losing muscle. 

Lofton: Nausea, hands down. It’s reported in 25% to 44% of patients, depending on which GLP-1, because the medication is actually slowing down the rate of stomach emptying. 

Next is constipation. That can come for many different reasons, but I encourage patients to make sure they're eating fiber, taking fiber supplements, and drinking water so that they can try to avoid constipation. 

Sometimes we do need to go to over-the-counter treatment, such as stool softener, magnesium, and things like that. There will be about 7% of people who cannot tolerate the medication due to gastrointestinal side effects.