The 71-year-old TV star started using weight-loss medication two and a half years ago, and she admits that GLP-1 has transformed her life.
Winfrey told People: "I thought it was about discipline and willpower. But I stopped blaming myself.
"I feel more alive and more vibrant than I've ever been."
Winfrey admits that she now feels happier in her own skin.
She said: "I'm not constantly punishing myself. I hardly recognise the woman I've become. But she's a happy woman."
By contrast, Winfrey previously felt "embarrassed" by her appearance.
She explained: "I've always been confident in whatever I was doing, but I was at the same time disappointed in my overweight body.
"Was I embarrassed by it? Yes. Was I disappointed in myself for continuing to fail? Yes, every single time. I felt it was my fault."
Meanwhile, Winfrey previously revealed that she once declined a party invite because she thought she was "too fat".
The TV star embarked on a weight-loss journey in the late 1980s - but Winfrey found that in spite of her best efforts, she quickly regained the weight that she'd lost.
During an appearance on The Jamie Kern Lima Show, Winfrey shared: "I didn't have a morsel of food for five solid months in losing that weight on (the all-liquid diet) Optifast.
"Three days later, I was 5 lbs (2 kg). heavier, and a week later I was 10 lbs (5 kg). heavier.
"The week before Christmas, I remember Don Johnson - Â the Don Johnson, of Miami Vice - was having a party and had invited me and some members of my show to come, and I wouldn't go because I thought I was too fat to go."
Winfrey recalled feeling a sense of shame about her weight struggles.
She said: "I'd gone from 145 (lbs,66 kg). on the day of the show. I think I was 157 (lbs, 71 kg). in the course of, like, a week and a half or two. And the shame started again."
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