Tirzepatide

Tirzepatide is the active ingredient in Mounjaro and Zepbound. It is a dual agonist: a single engineered peptide that switches on both the GIP receptor and the GLP-1 receptor. Semaglutide and liraglutide act on GLP-1 alone. That second receptor is the structural reason tirzepatide has produced larger average weight reductions in trials.

The head-to-head evidence is now direct. SURMOUNT-5 randomized 751 adults with obesity and no diabetes to tirzepatide or semaglutide for 72 weeks; average weight change was −20.2% versus −13.7%, and waist circumference fell 18.4 cm versus 13.0 cm. In type 2 diabetes, SURPASS-2 found tirzepatide superior to semaglutide 1 mg on A1C at every dose tested. Superior on average does not mean superior for every individual, and tolerability often decides which drug someone actually stays on.

Tirzepatide’s elimination half-life is about five days, shorter than semaglutide’s week but still long enough for once-weekly injection. Doses run 2.5 mg through 15 mg weekly in 2.5 mg increments, with at least four weeks between steps. Because the strengths are identical across the two brands, the brand-switch calculator is mostly about paperwork rather than pharmacology.

The usual confusion is the phrase “dual agonist” being read as “twice as strong.” It is not a dose multiplier — it is a different receptor profile, and the gastrointestinal side-effect burden in trials was broadly comparable to GLP-1-only drugs, concentrated during dose escalation. A second confusion: tirzepatide is not a “GLP-2” or a triple agonist, though retatrutide in development is.

Useful questions for a visit: whether your prescriber is aiming for 10 mg or 15 mg and why; whether side effects during escalation should trigger a pause at the current dose rather than a jump; and how muscle will be protected across a 20% loss. Our SURMOUNT-5 analysis and the tirzepatide drug page go deeper.