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My general framework: Start with semaglutide if cost is a significant concern, or if there is no strong reason to expect poor tolerance Start with tirzepatide if the patient has tried semaglutide before and struggled with side effects, if faster initial response matters clinically, or if the patients goals require larger total weight loss Switch to tirzepatide if a patient on semaglutide is experiencing persistent nausea or has plateaued and escalation options are limited One pattern worth noting: men I see a consistent pattern with male patients who struggle to tolerate semaglutide nausea and GI disruption can be particularly disruptive for them, and theyre often less willing to push through it

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