someone in r/Mounjaro posted a 300lb loss over about 11 months, started on sema, switched to tirz. the comments are doing the usual “sema vs tirz which is better” thing and i don’t think that’s the interesting question for someone at that magnitude of loss. the interesting question is what happens at month 18, 24, 36. so i pulled SURMOUNT-4 again. for anyone who hasn’t read it: 36 wks open-label tirz lead-in, then randomized continuation vs placebo for another 52 wks. the continuation arm kept losing (got to roughly -25% from baseline). the placebo-switch arm regained about 14 percentage points back. people quote that number a lot. what gets cited less: - the regain curve isn’t linear. most of it lands in the first ~20 wks post-switch, then flattens. so the “i’ll just stay off it for a few months” plan is basically choosing the steepest part of the slope.
- variance in the regain arm was large. some participants held most of their loss; others were almost back to baseline by wk 88. the trial isn’t powered to tell you which bucket you’re in.
- it was a placebo switch, not a taper. nobody knows what a structured down-titration does to that curve bc nobody’s run it. (i’d kill for that trial.) for someone down 300lbs the absolute stakes of that 14% regain are different than for someone down 40. 14% of 488 is ~68lbs. that’s not a vanity number, that’s a comorbidity number. none of this is a reason to stay on a drug forever, fwiw. it’s a reason to be honest that the off-ramp is the part of the protocol nobody’s actually studied. the trial designs end where the hard question starts. anyone seen a structured taper protocol in the literature i’ve missed?