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When GLP-1 Therapy Stops Working Most patients on GLP-1 therapy experience a predictable trajectory: rapid initial weight reduction followed by a gradual slowing of progress

However, the largest Phase IIb trial involving 536 subjects failed to demonstrate statistically significant weight loss compared to placebo at the primary 12-week endpoint, leading Metabolic Pharmaceuticals to terminate development in 2007

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This occurs because the enzyme, dihydrofolate reductase, has limited capacity to reduce folic acid in mammalian cells, particularly in human cells (68)