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Both Rybelsus and Januvia enhance incretin hormone activity, but through different mechanisms: Rybelsus directly activates GLP-1 receptors to stimulate insulin secretion when blood glucose levels are high, while Januvia works by preventing the breakdown of naturally occurring incretin hormones, thereby enhancing insulin secretion and suppressing glucagon release
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A direct head-to-head trial is underway (with initial results due later in 2026), and current data shows that when the highest dose of each drug is taken over a 72-week period, those on tirzepatide returned a higher percentage of total body weight loss (20.2% - 21.1% as opposed to 13.7% - 14.1% for semaglutide (as detailed in the New England Journal of Medicine Study of May 2025)
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