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Reason 1.) Wegovy pill's 16.6% weight loss has to be taken into context. That number comes from the OASIS-4 trial which only had 307 patients, 79% were female, and 92% were white. By comparison, the ATTAIN-1 trial for orforglipron had 3127 patients, 64% female, and 57% white. In orfo's phase 2 they achieved 13.5% weight loss at 36 weeks. That study had 272 patients, 59% female, 91% white. There is increasing data that suggests females and whites respond better to GLP drugs. So given the small amount of people in the trial, and the fact that there was an over-representation of the most responsive patient type, one can see how the deck was stacked in their favor to get that 16.6% number. And one can see how this won't be representative of a global population.
Reason 2.) We actually have a head-to-head trial in ACHIEVE-3. Yes it was in a diabetic population, but that's a good thing, because diabetics are harder to treat for weight loss. In ACHIEVE-3, if we take out the higher 36mg dose of orfo, we can still see that the 12mg orfo dose (6.7% weight loss) beat the 14mg sema dose (5.3%). Novo did their own diabetic trial for oral sema in PIONEER PLUS and lo and behold they got 4.7% weight loss for 14mg, and 8.2% for 25mg and 9.6% for 50mg. compare that to the 9.2% weight loss from 36mg orfo and all the data suggests orfo will be as good, if not even better, than oral sema (at the least in diabetics).
Reason 3.) Results of the ATTAIN-MAINTAIN trial just came out and when patients switched from Wegovy 1.7/2.4mg to orfo 36mg, they gained back a whopping 1% of their weight. In contrast, the Zepbound 10/15mg arm of the study gained back 5% of their weight. The strangest number is that both arms ended up with the exact same weight by the end of the trial. If you average it out, napkin math says it's 16% weight loss. This suggests that orfo will stabilize at around that mid teens number that we keep seeing.
In conclusion, when you look further and further into the data, we will arrive at a logical assertion, that sufficient GLP agonism will get you to that mid teens weight loss number. Orforglipron will achieve a very similar efficacy to Wegovy pill in the real world.