Wilding J.P.H. et al.
Editor's note
The trial that turned semaglutide into a household word. 14.9% mean body-weight reduction at 68 weeks vs. 2.4% on placebo across 1,961 adults — the result that opened the floodgates for the entire GLP-1 wave.
Related literature
Lincoff A.M. et al.
The first hard-endpoint cardiovascular outcomes trial of a GLP-1 in non-diabetics. 17,604 patients with prior CV disease and BMI ≥27; 20% relative reduction in MACE at mean 39.8 months. This is the paper that moved semaglutide from a weight-loss drug to a cardiovascular drug.
Jastreboff A.M. et al.
Tirzepatide's coming-out party. At the 15 mg dose, participants lost a mean 22.5% of body weight over 72 weeks across 2,539 adults without diabetes — numbers that approach bariatric-surgery territory and reset every expectation for pharmacotherapy.
Aronne L.J. et al.
The head-to-head everyone was waiting for. 751 adults over 72 weeks: 20.2% weight loss with tirzepatide vs. 13.7% with semaglutide at max tolerated doses — a 6.5-point gap that's clinically meaningful but smaller than the marketing suggests. Both drugs work; tirzepatide works more.
Sanyal A.J. et al.
ESSENCE Part 1 hit both primary endpoints at 72 weeks: MASH resolution without fibrosis worsening, and fibrosis improvement without MASH worsening. This is what got semaglutide an FDA MASH indication and made GLP-1s a liver story too.
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