Quick Answer The key difference is that Mounjaro (tirzepatide) acts on two appetite-regulating hormones, GIP and GLP-1, while Wegovy (semaglutide) acts on GLP-1 alone. Clinical trial data, including the head-to-head SURMOUNT-5 trial, shows Mounjaro produces greater average weight loss. However, both are effective, MHRA-approved treatments and the right choice depends on individual health history, tolerability, …