Dr. Charles Mok explains how semaglutide and tirzepatide cause rapid tolerance, forcing dose increases from 0.25 mg to 2.4 mg. Most weight loss happens in the first 12 to 13 weeks, and tolerance can fade within 2 to 6 weeks.
Go back to the idea of tolerance and extinction of tolerance. So when you're taking a GLP1 agonist, such as semaglutide, let's go for tirzepatide as well, which has two different pathways. These drugs have a rapid tolerance where your body gets kind of used to it, your body gets used to the drugs. You have to keep escalating the dose. If you start out semaglutide at the maintenance dose, you get very sick. You'll feel terrible. It's not going to kill you or anything, but it makes you feel terrible. Because of that and the tolerance that does occur, we start at a very small dose, which is 0.25 milligrams. We wind up at a dose of 2.4 milligrams. So 0.25 to start and 2.4 to 2.5 milligrams to finish. Most of the weight loss occurs in the earlier phases of the use of the semaglutide. In other words, in the first 12 or 13 weeks, that's where we see most of it occur. And the tolerance actually extinguishes or goes away very quickly, as soon as two weeks, but pretty significantly at about four to six weeks.
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