"If you try to lose weight with diet and exercise, your body is going to fight you," said Dr. Caroline Apovian, co-director of the Center for Weight Management and Wellness at Brigham and Women's Hospital in Boston. "Your leptin levels go down, and when leptin goes down, a signal goes to the brain that you don't have enough fat to survive." That prompts the release of another hormone, ghrelin, that triggers feelings of hunger.

Leptin resistance also makes exercise less worthwhile.

"Your body fights you by decreasing your total energy expenditure," Apovian said. "When your muscles work, they work more efficiently. If you want to lose 10 pounds, you're going to get really, really hungry. And you can't fight that. Your body thinks it's starving to death."

The "breakthrough" drugs counteract this by impersonating a hormone called glucagon-like peptide 1, or GLP-1, that's involved in appetite regulation. Inside cells, the drugs bind with the same receptors as GLP-1, reducing blood sugar and slowing digestion. They also last longer than their natural counterparts.

The first so-called GLP-1 receptor agonist was approved in 2005 to treat diabetes, and early versions had to be injected once or twice a day. Ozempic improved on this by requiring an injection only once a week. After clinical trials showed that the drug helped people with obesity achieve substantial, sustainable weight loss, the FDA approved Wegovy as a weight management drug in 2021.

Mounjaro and Zepbound also mimic GLP-1, along with a related hormone called glucose-dependent insulinotropic peptide, or GIP.

Linda Morales credits Ozempic and Mounjaro for helping her lose 100 pounds and drop from a size 22 to a size 14. The 25-year-old instructional aide at Lankershim Elementary School in North Hollywood said she started to become overweight in middle school and carried 293 pounds on her 5-foot, 5-inch frame when she was referred to the Center for Weight Management and Metabolic Health at Cedars-Sinai two years ago.

She is no longer breathless when she climbs stairs, has an easier time when she goes bowling and fits comfortably into the seat on the Harry Potter ride at Universal Studios. Thanks to the medications, she is no longer on a path toward Type 2 diabetes.

Her job with the Los Angeles Unified School District comes with health insurance that covers the pricey drugs and charges her a copay of $30 a month for her Mounjaro prescription. She said she could swing a monthly payment of up to $50, but beyond that she'd have to stop taking the drug and hope the lifestyle changes she'd made would be enough to sustain the weight loss she's achieved so far.

"It would definitely get hard for me, for sure," Morales said.

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