JUANA SUMMERS, HOST:

GLP-1 injectable drugs like Wegovy and Zepbound have transformed obesity treatment as well as some patients’ bodies. But not everyone loses lots of weight. NPR’s Yuki Noguchi reports on the many reasons why.

YUKI NOGUCHI, BYLINE: Obesity shaped Anna Olson’s earliest notions of herself.

ANNA OLSON: Looking at a picture of myself and thinking to myself, like, oh, I look different than the other kids.

NOGUCHI: Her obesity began in toddlerhood and ran in her family. It left her with a chronic hunger hard to satiate. Dozens of diet, drug and exercise regimens didn’t work. Olson was told…

OLSON: You know, you got to just eat less. You got to eat less. You got to do this. And I’m kind of like, well, that’s what I’m doing now. Like, what else can I do? Well, you just got to eat less.

NOGUCHI: In fact, obesity is far more complex. It has many biological and behavioral factors that must be identified, then addressed for each person. For Olson, genetic testing indicated she likely has several genetic and hormonal factors setting her hunger and satiety sensors out of whack. One of the GLP-1 drugs – Ozempic – worked briefly. But it turned out another – Zepbound – better recalibrated Olson’s hormone imbalance. It was only when she started tackling her specific obesity drivers that Olson began losing lots of weight – 65 pounds to date.

OLSON: And I’ve been able to keep it off.

NOGUCHI: Use of the GLP-1 drugs is set to explode as they become cheaper, with more variations and in pill form. Within a few years, doctors say, there will also be ways to determine an individual’s obesity factors. That would allow them to target the root causes of obesity the same way chemotherapies can target specific cancers. Anna Olson says this personalization was key. Now 36, Olson says she’s closer to her dream of traveling further afield of her native Minneapolis.

OLSON: And be able to walk around and see and do things. When I was, like, more overweight, there was absolutely no way that I could do that.

NOGUCHI: Dr. Lydia Alexander is past president of the Obesity Medicine Association. She says people’s response to GLP-1s reveals just how different obesity is for each person.

LYDIA ALEXANDER: Not everyone arrives at obesity in the same way.

NOGUCHI: Alexander says everything from a person’s gut microbiome, their proclivity toward addiction or the molecular shape of their hormone receptors can affect the drug’s efficacy.

ALEXANDER: The medication might be degraded faster in one individual than another.

NOGUCHI: And Alexander says in all instances, adaptations in lifestyle are critical for a full and lasting response. The problem, Dr. Jennifer Manne-Goehler says, is GLP-1s raised people’s expectations for weight loss. Manne-Goehler, a Harvard metabolic disease specialist, says roughly half of those who take GLP-1 drugs lose 15% or more of their weight.

JENNIFER MANNE-GOEHLER: The problem is, because the potential of those drugs is so incredible for that half, everyone who takes them thinks they’re going to be in the half that have that experience.

NOGUCHI: Manne-Goehler says what’s often forgotten is that obesity is a chronic, lifelong condition.

MANNE-GOEHLER: One tool does not work for each person. And one tool often is not enough over the lifetime of a person to control or to mitigate the health impact of that condition.

NOGUCHI: But in a few years, she says, at least there will be tools to better target treatment.

Yuki Noguchi, NPR News.

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