Tirzepatide
Tirzepatide (dual GIP/GLP-1 receptor agonist)
Also known as: Mounjaro, Zepbound
A first-in-class dual GIP and GLP-1 receptor agonist with superior weight loss and glycemic control versus GLP-1 mono-agonists.
Overview
Tirzepatide is a once-weekly dual agonist that activates both the GIP and GLP-1 receptors. In head-to-head and placebo-controlled trials it produced greater weight loss and glycemic improvement than GLP-1 mono-agonists, with roughly 21% mean body weight reduction at the 15 mg dose over 72 weeks in SURMOUNT-1. Update, September 2026: Mounjaro gained an FDA indication in August 2026 to reduce major adverse cardiovascular events in adults with type 2 diabetes (SURPASS-CVOT).
Mechanism of action
Simultaneously activates GIP and GLP-1 receptors, enhancing glucose-dependent insulin secretion, reducing glucagon, delaying gastric emptying, and reducing appetite. The GIP component is thought to add complementary metabolic effects.
Key studies & citations
- Human2022
Tirzepatide Once Weekly for the Treatment of Obesity (SURMOUNT-1)
2,539 adults without diabetes: mean weight change at 72 weeks of -15.0% (5 mg), -19.5% (10 mg) and -20.9% (15 mg) versus -3.1% with placebo.
New England Journal of Medicine - Human2021
Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes (SURPASS-2)
1,879 patients over 40 weeks: all tirzepatide doses were noninferior and superior to semaglutide 1 mg for HbA1c, with greater weight loss (up to -5.5 kg more at 15 mg).
New England Journal of Medicine - Human2025
Cardiovascular Outcomes with Tirzepatide versus Dulaglutide in Type 2 Diabetes (SURPASS-CVOT)
13,299 patients with type 2 diabetes and atherosclerotic disease: primary MACE in 12.2% on tirzepatide vs 13.1% on dulaglutide (HR 0.92), meeting noninferiority against an active comparator with proven benefit; basis of the August 2026 cardiovascular indication.
New England Journal of Medicine - Human2024
Tirzepatide for the Treatment of Obstructive Sleep Apnea and Obesity (SURMOUNT-OSA)
Two phase 3 trials in moderate-to-severe OSA with obesity: apnea-hypopnea index fell by about 25 events per hour at 52 weeks versus placebo, supporting the Zepbound sleep apnea indication.
New England Journal of Medicine
Frequently asked questions
How is tirzepatide different from semaglutide?
Tirzepatide activates two receptors (GIP and GLP-1) rather than GLP-1 alone, and in trials produced greater average weight loss and glucose lowering.