Rosie O’Donnell says Mounjaro is part of why she’s ‘never felt better’ at 64

• Rosie O'Donnell said she has "never felt better" than at 64 — and it's partly due to Mounjaro.
• O'Donnell said her doctor first recommended the drug to help manage her diabetes.
• She said the subsequent weight loss caught her off guard: "I had never lost weight for no reason."

At 64, Rosie O'Donnell said she's reached a place where she feels healthier and more comfortable in her body.

"I never felt better. And it's sad to me that it took me till I was 64 to get here, but part of it is Mounjaro," O'Donnell said on Tuesday's episode of the "Good Hang with Amy Poehler" podcast.

The actor and talk show host said her doctor first introduced her to the drug three years ago to help manage her diabetes.

"Never mentioned weight loss. Never said anything because it was my numbers they were trying to get down," O'Donnell said.

Not long after starting the medication, O'Donnell said she noticed its effects during a celebratory dinner for her son's engagement.

"I take the shot, and I go out to Nobu, and I can't eat anything," she said, adding that she initially thought her lack of appetite was due to feeling emotional and wishing her late mother could have shared in the occasion.

The weight loss that followed was so unexpected that O'Donnell said she feared something was wrong.

"Cut to two weeks later, I get on the scale. I call my doctor crying, I must have cancer. I've lost 12 pounds, and I haven't done anything," she said.

"I had never lost weight for no reason," O'Donnell said, adding that losing weight had always been difficult for her, even when she was actively trying to do so.

The FDA approved Mounjaro, which contains tirzepatide, for type 2 diabetes in 2022. A year later, it approved the same drug for chronic weight management under the brand name Zepbound.

Like semaglutide, the active ingredient in Ozempic and Wegovy, tirzepatide activates receptors for GLP-1, a gut hormone that helps regulate blood sugar and appetite. Unlike semaglutide, tirzepatide also activates receptors for another hormone, GIP.

Tirzepatide and semaglutide can cause similar side effects, including gastrointestinal symptoms such as nausea and diarrhea.

O'Donnell is one of several celebrities who have opened up about their experiences taking GLP-1 medications.

In May 2025, "Modern Family" star Eric Stonestreet told Business Insider that taking Mounjaro for his diabetes ultimately motivated him to adopt a healthier lifestyle. He said he started moving for 150 minutes a week.

"All of a sudden, I felt like I needed to be accountable to it, because it's showing up every day to do something for me," Stonestreet said.

In August 2025, Serena Williams said she turned to a GLP-1 after struggling to lose weight following childbirth, despite exercising and eating healthily.

"I lost over 31 pounds using my GLP-1 and I was really excited about that weight loss," Williams said.

In January, Oprah Winfrey said she regrets not using GLP-1s sooner to manage her weight.

"I think about the wasted years," Winfrey said.