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Genetic variants in CYP3A4 and other metabolizing enzymes mean some patients clear the medication too quickly, reducing its circulating levels below the threshold needed for meaningful appetite suppression

Key Observations from Phase 2 Data Dose escalation reduced adverse events: Groups that used gradual dose titration reported fewer GI events than those starting at the target dose directly No deaths were attributed to the study drug Serious adverse events were reported at low rates across all groups, with no clear dose-dependent pattern for serious events The placebo group also reported substantial adverse events (72.1%), which is typical for trials of this size and duration TRIUMPH Phase 3 Adverse Event Profiles The TRIUMPH program consists of eight Phase 3 trials evaluating retatrutide across multiple indications including obesity, type 2 diabetes, and metabolic-associated steatotic liver disease (MASLD)

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From another perspective, our findings serve as reverse evidence that further positively supports the consistent results presented by numerous international studies so far: GLP-1RA treatment can indeed bring cardiovascular benefits and safety to diabetic patients