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While some receptor adaptation does occur (explaining why gastric emptying effects attenuate over time even as doses increase), the central appetite-suppressing effects appear to be maintained through mechanisms that do not rely solely on gastric motility

Early evidence is limited to case reports, resulting in the lack of definitive management guidelines for patients on GLP-1 or GLP-1/GIP receptor agonists

The study used a reverse translational approach, starting with observations from human use and testing specific mechanisms in controlled animal experiments

The TRANSCEND-T2D-1 trial adds a second pressure point: 16.8% body weight reduction in patients with type 2 diabetes, a population that consistently underperforms on weight-loss endpoints with existing agents

Hypoglycemia: When used with other medications that increase insulin levels, such as sulfonylureas, the risk of hypoglycemia (low blood sugar) increases

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