Semaglutide vs tirzepatide

How do semaglutide and tirzepatide differ mechanically?

Tirzepatide is a dual GIP and GLP-1 receptor agonist [1], while Wegovy's label describes semaglutide as a GLP-1 receptor agonist and advises against combining it with any other GLP-1 receptor agonist [3]. Both Mounjaro and Zepbound are given only as once-weekly subcutaneous injections, with no FDA-approved oral tirzepatide form [1][2]. Semaglutide, by contrast, comes as an injection (Ozempic, Wegovy) and as a tablet, with Wegovy tablets on the Wegovy label [3][4]; see oral GLP-1 medications.

How do their approved uses differ?

Mounjaro is approved for glycemic control in type 2 diabetes, and Ozempic injection adds approved indications for cardiovascular and kidney risk reduction in adults with type 2 diabetes [1][4]. Zepbound is approved for chronic weight management and moderate to severe obstructive sleep apnea [2]. Wegovy is approved for chronic weight management, cardiovascular risk reduction, and, for the injection only, a liver condition called MASH [3].

Which produced bigger changes in a head-to-head trial?

In SURPASS-2, a 40-week trial in adults with type 2 diabetes, tirzepatide's three doses reduced HbA1c by 2.0% to 2.3% and body weight by 7.6 kg to 11.2 kg, compared with 1.9% and 5.7 kg for semaglutide 1 mg [1]. That trial compared a diabetes dose of semaglutide, not Wegovy's weight-management dose, so it does not settle which drug works better for weight loss alone [1].