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nausea common but usually mild Weeks 5-12 (0.5 to 1.0 mg doses): Accelerated weight loss, 0.5-1% of body weight per week Appetite suppression becomes pronounced This is the phase where patients report "forgetting to eat" or feeling full after small portions Cumulative weight loss by week 12: 5-8% of baseline body weight Weeks 13-28 (1.7 to 2.4 mg doses): Continued weight loss at 0.3-0.5% per week Rate of loss slows compared to weeks 5-12, but total loss continues to accumulate Cumulative weight loss by week 28: 10-13% of baseline body weight Weeks 29-68 (2.4 mg maintenance): Weight loss continues but at a slower rate, approximately 0.1-0.2% per week Most patients plateau between weeks 60 and 68 Final cumulative weight loss: 14-17% of baseline body weight in trial populations, 12-15% in real-world populations Beyond 68 weeks: Weight typically stabilizes if treatment continues STEP 5 data shows no further significant loss after week 68, but also no regain if medication continues Discontinuation results in gradual weight regain, with most patients returning to 50-70% of their original weight within 12 months (STEP 4 data) Individual variation is substantial

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In some embodiments, the otic formulation or composition comprises between about 0.001% to about 15% by weight of the therapeutic agent, or pharmaceutically acceptable prodrug or salt thereof