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The adaptation timeline: what to expect week by week Week 1 to 2 (initiation dose, 2.5 mg): 40 to 50% of patients who will experience injection site reactions have their first one during this window Redness and swelling peak at 12 to 24 hours post-injection Itching is most common complaint Reactions typically last 48 to 72 hours Second injection often produces a milder reaction than the first Week 3 to 4 (still at 2.5 mg): Reaction rate drops to 20 to 30% of patients Severity decreases (smaller area of redness, less itching) Duration shortens (24 to 48 hours instead of 72) Most patients notice the pattern: "It's getting better each time" Week 5 to 8 (escalation to 5 mg): Dose escalation can re-trigger reactions in 10 to 15% of patients who had adapted at 2.5 mg Higher dose means more tirzepatide protein at the injection site, which can restart the immune learning process Reactions during escalation are typically milder than initial reactions Adaptation at the new dose happens faster (2 to 3 weeks instead of 4 to 6) Week 9 to 12 (stable at 5 mg or escalating to 7.5 mg): Reaction rate stabilizes at 3 to 5% Most patients who experienced early reactions no longer have them Persistent reactions at this point suggest technique issues or rare delayed hypersensitivity Week 13+ (maintenance dose): Baseline reaction rate matches placebo (around 3%) New-onset reactions after 12+ weeks of stable dosing are uncommon and warrant evaluation If reactions suddenly return after months of no issues, consider contamination, injection site infection, or formulation change The timeline above reflects pooled data from SURPASS-1 and SURMOUNT-1