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Phase 1b/2a Subcutaneous Formulation (Obesity) Published: The Lancet, June 2025 Participants: 125 adults with overweight or obesity (BMI 27.039.9), aged 1855 Duration: Up to 36 weeks Dosing: Once-weekly subcutaneous amycretin, up to 60 mg Results: - Up to 22% absolute weight loss at 36 weeks (highest dose group) - Placebo-adjusted difference: approximately 24% - No weight-loss plateau observed at study end Safety: 81% of the 89 participants who reported a TEAE had gastrointestinal events

Zepbound should not be used in combination with other GLP-1 receptor agonists, as the safety and efficacy of such combinations have not been established

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Therefore, we could not perform a stratified MR analysis to explore the effects within these specific subgroups

Eating smaller, more frequent meals and avoiding high-fat foods may help manage gastrointestinal side effects

One important debate concerns the mechanisms underlying GLP-1RA benefits in non-metabolic diseases